Biology subjects

Xia, P.

Publications and source records attributed to Xia, P..

17 recordsLinked to original sources

bioRxiv2026

Factors underlying creativity show distinct genetic architecture and genetic correlations with psychiatric disorders

While creativity is widely recognized as multifaceted, genome-wide association studies have largely focused on individual measures. Here, we used genomic structural equation modeling of six creativity-related GWASs and identified two latent genetic factors: a general factor and an artistic factor, with 22 and 13 genome-wide significant loci, respectively, nine of which are novel. The general factor was almost perfectly genetically correlated with educational attainment (rg = 0.96), suggesting that it primarily captured genetic influences shared with cognitive and educational processes rather than creativity-specific variation. In contrast, the artistic factor showed only a weak genetic correlation with educational attainment (rg = 0.11) and consistent positive genetic correlations with psychiatric disorders, whereas associations for the general factor were largely null or negative. Biological annotation analyses further identified distinct enrichment patterns unique to the artistic factor, providing initial evidence that different dimensions of creativity may be characterized by partially distinct neurobiological pathways.

genomics↗

bioRxiv2026

Physiological Aging and Cardiovascular Disease Distinctly Remodel the Human Cardiac Lymphatic Endothelium

Aims: Cardiac lymphatic endothelial cells (LECs) regulate tissue homeostasis, immune trafficking, and remodeling, but how human cardiac LEC heterogeneity changes with physiological aging and cardiovascular disease remains poorly defined. We sought to define age- and disease-associated LEC states, their regulatory and microenvironmental programs, and the functional relevance of selected pathways. Methods and results: We integrated human cardiac single-nucleus transcriptomic datasets spanning physiological aging, dilated and hypertrophic cardiomyopathy, doxorubicin-associated cardiomyopathy, and heart failure with preserved ejection fraction. Aging redistributed LECs among pre-existing states, with expansion of a homeostatic immune-surveillance state and loss of cytokine-responsive and polarity-associated states. Cardiovascular diseases showed a distinct trajectory, with depletion of a non-failing homeostatic state and expansion of shared and disease-associated remodeling states. SCENIC and NicheNet/MultiNicheNet identified state-specific regulatory programs and disease-dependent signaling networks, with recurrent BMP/TGF-{beta}/activin-family signaling. ACVR2A was prioritized in human doxorubicin-associated cardiomyopathy; endothelial Acvr2a deletion in aged doxorubicin-treated mice was associated with improved cardiac function and increased open cardiac lymphatic vessels. Independent human spatial transcriptomic analyses supported selected aging- and disease-associated programs. Conclusion: Physiological aging and cardiovascular disease remodel cardiac LECs through distinct changes in cellular state, transcriptional regulation, and microenvironmental signaling. Aging is associated with redistribution and reduced representation of specialized LEC programs, whereas cardiovascular diseases redirect LECs through disease-associated signaling environments, highlighting context-dependent remodeling of the cardiac lymphatic endothelium across aging and disease.

bioinformatics↗

bioRxiv2026

A U1-U3 snRNA-snoRNA interaction couples SF3B1 mutation to chromatin-state rewiring and genome instability

Mutations in spliceosome factors such as SF3B1 are recurrent across human diseases, including myelodysplastic syndromes and leukemia1-4, yet splicing defects alone do not fully explain the widespread chromatin alterations and genome instability in mutant cells5. Here, by comprehensively mapping snRNA-directed RNA-RNA interactions, we identify two previously unrecognized interaction motifs in U1 snRNA beyond canonical 5' splice-site pairing6,7. These motifs enable U1 RNA to i) bind intronic and other chromatin-associated RNA (caRNA) regions outside of splice sites, and ii) base pair specifically with snoRNA. We uncover a U1-U3 snRNA-snoRNA interaction that recruits the H3K36 methyltransferase SETD2 to caRNA, promoting gene-body H3K36me3 and antagonizing H3K27me3 to modulate chromatin accessibility. The snRNA-snoRNA interface is essential for this previously unrecognized layer of chromatin and transcriptional regulation mediated through SETD2. SF3B1 mutation enhances U1-U3 binding and increases the association of the U1-U3 complex with caRNA, driving chromatin-accessibility remolding, R-loop formation, DNA damage, and copy-number abnormalities that promote tumorigenesis. A U1-specific 2'-O-methoxyethyl antisense oligonucleotide that selectively blocks U1-U3 pairing suppresses these genomic abnormalities, reduces leukemic infiltration, and prolongs survival in xenograft and patient-derived models, establishing pathological snRNA-snoRNA rewiring as a critical driver of SF3B1-mutant leukemogenesis.

cell biology↗

bioRxiv2026

Daikenchuto modulates gut microbial metabolism to mitigate irinotecan-induced enterotoxicity

Gut microbiota metabolic remodeling is a pivotal determinant in irinotecan-induced enterotoxicity and epithelial damage, although the underlying mechanisms remain unclear. Herein, we discovered that Daikenchuto (DKT), a traditional Chinese prescription for intestinal disorders, alleviated irinotecan-induced enterotoxicity without compromising its anti-tumor efficacy by improving weight loss, diarrhea, intestinal inflammation, and barrier damage, and these effects were partially dependent on gut microbiota. DKT significantly restored microbial tryptophan metabolism in irinotecan-treated rats, which was characterized by the enrichment of Limosilactobacillus reuteri, and elevated levels of indole-3-ethanol (IE) and indole-3-propionic acid (IPA). Multi-omics analysis further revealed a positive correlation between L. reuteri and IE and IPA. Consistent with this, DKT promoted L. reuteri proliferation, leading to the conversion of tryptophan to IE and IPA, which improved epithelial barrier damage in the irinotecan-treated Caco-2 cells. In addition, DKT suppressed the growth of Loop 1 {beta}-glucuronidase ({beta}-GUS)-producing bacteria, such as Escherichia coli. Furthermore, the main constituents of DKT selectively inhibited Loop 1 {beta}-GUS activity independent of the gut microbiota, which reduced the intra-luminal level of 7-ethyl-10-hydroxycamptothecin, the toxic metabolite of irinotecan. Taken together, this study reveals a dual gut microbiota-driven mechanism by which DKT mitigates irinotecan-induced enterotoxicity, which provides a promising strategy for managing chemotherapy-related enterotoxicity.

pharmacology and toxicology↗

bioRxiv2025

Lysine-R2HGylation identified as a post-translational modification in R2HG-elevated cancers

R-2-Hydroxyglutarate (R2HG), an oncometabolite predominantly produced by mutated isocitrate dehydrogenase 1/2 (IDH1/2) in various cancers, is known to drive cancer progression through noncovalent inhibition of -ketoglutarate (KG)-dependent enzymes. In this work, we propose an alternative mechanism wherein R2HG contributes to cancer development via covalent modification of biologically critical lysines, a process termed lysine-R2HGylation (KR2HG). We designed and synthesized R2HG-mimicking probes, demonstrating their effectiveness in facilitating KR2HG target profiling and site mapping. We identified KR2HG as a previously unrecognized post-translational modification, confirmed its C5-linkage on GSTP1(K209), and demonstrated that SIRT5 functions as a deacylase for GSTP1-KR2HG in vitro. Furthermore, we found that R2HG slightly but significantly inhibits the enzymatic activity of GSTP1 through KR2HG and dramatically suppresses monocyte differentiation via this catalytically important lysine modification. Our findings provide an alternative perspective on the role of R2HG in leukemia progression and offer a practical tool for the clinical investigation of R2HG-elevated cancers.

molecular biology↗

bioRxiv2024

A VgrG2b fragment cleaved by caspase-11/4 promotes Pseudomonas aeruginosa infection through suppressing the NLRP3 inflammasome

The T6SS of Pseudomonas aeruginosa plays an essential role in the establishment of chronic infections. Inflammatory cytokines mediated by inflammasomes are crucial for the body to resist bacterial infections. Here we found that during the infection of P. aeruginosa, non-canonical inflammasome was activated in macrophages, but the activation of downstream NLRP3 inflammasome was inhibited. The VgrG2b of P. aeruginosa is recognized and cleaved by caspase-11, generating a free C-terminal fragment. The VgrG2b C-terminus can bind to NLRP3, inhibiting the activation of the NLRP3 inflammasome by rejecting NEK7 binding to NLRP3. Administrating a specific peptide that inhibits the cleavage of VgrG2b by caspase-11 to mice can significantly improve their survival rate during infection. Our discovery elucidates a mechanism by which P. aeruginosa inhibits host immune response, providing a new approach for the future clinical treatment of P. aeruginosa infections.

immunology↗

bioRxiv2024

Contraction-induced endocardial id2b plays a dual role in regulating myocardial contractility and valve formation

Biomechanical cues play an essential role in sculpting organ formation. Comprehending how cardiac cells perceive and respond to biomechanical forces is a biological process with significant medical implications that remains poorly understood. Here we show that biomechanical forces activate endocardial id2b (inhibitor of DNA binding 2b) expression, thereby promoting cardiac contractility and valve formation. Taking advantage of the unique strengths of zebrafish, particularly the viability of embryos lacking heartbeats, we systematically compared the transcriptomes of hearts with impaired contractility to those of control hearts. This comparison identified id2b as a gene sensitive to blood flow. By generating a knockin reporter line, our results unveiled the presence of id2b in the endocardium, and its expression is sensitive to both pharmacological and genetic perturbations of contraction. Furthermore, id2b loss-of-function resulted in progressive heart malformation and early lethality. Combining RNA-seq analysis, electrophysiology, calcium imaging, and echocardiography, we discovered profound impairment in atrioventricular (AV) valve formation and defective excitation-contraction coupling in id2b mutants. Mechanistically, deletion of id2b reduced AV endocardial cell proliferation and led to a progressive increase in retrograde blood flow. In the myocardium, id2b directly interacted with the bHLH component tcf3b (transcription factor 3b) to restrict its activity. Inactivating id2b unleashed its inhibition on tcf3b, resulted in enhanced repressor activity of tcf3b, which subsequently suppressed the expression of nrg1 (neuregulin 1), an essential mitogen for heart development. Overall, our findings identify id2b as an endocardial cell-specific, biomechanical signaling-sensitive gene, which mediates intercellular communications between endocardium and myocardium to sculpt heart morphogenesis and function.

developmental biology↗

bioRxiv2024

Rice OsPLATZ3 controls ROS homeostasis by inhibiting ROS-Scavenging Activity during Tapetum Degeneration

OsPLATZ3, a transcription factor of rice (Oryza sativa) belonging to the PLATZ family, is involved in the repression of transcriptional activity. PLATZ3 exhibits preferential expression in the tapetal cells during anthers development, regulating tapetum degeneration by controlling the dynamics of reactive oxygen species (ROS) in rice male reproductive processes. The Osplatz3 exhibits enlarged tapetum with delayed degeneration, significantly lower ROS levels from S5 to S12 in anthers compared to the wild-type, resulting in complete male sterility. In the anthers of Osplatz3, there are significant changes in the regulators of programmed cell death (PCD)-induced tapetal degradation, such as TDR, EAT1, and their effectors OsCP1, OsC6, OsAP25, and OsAP37. These findings indicate that OsPLATZ3 is a new addition to the tapetum PCD regulatory network. In the late stages of anthers development, Osplatz3 exhibits phenotypes associated with oxidative stress. Transcriptome analysis revealed significant differential expression in 229 genes associated with maintaining ROS homeostasis. Furthermore, Electrophoretic Mobility Shift Assay (EMSA) demonstrate that OsPLATZ3 can bind to the promoter region of OsAPX9, a gene encoding a plant ascorbate peroxidase domain protein with putative ROS scavenging capabilities. These findings suggest that OsPLATZ3 serves as a crucial regulatory factor in tapetum PCD by suppressing ROS scavenging activity.

plant biology↗

bioRxiv2023

iTie controls intestinal tolerance through suppressing the NLRP6 inflammasome

Intestines are full of commensal bacteria that possess numerous pathogen-associated molecular patterns. How the intestinal epithelial cells are tolerant to these stimuli under normal conditions is still elusive. Here we show that iTie is expressed in small intestinal enterocytes and its deficiency leads to body weight loss in mice, accompanied by length reduce of small intestines and intestinal villi. The activation of NLRP6 inflammasome is exacerbated upon iTie deletion. iTie has a higher binding affinity for NLRP6 than NLRP6s physiological ligand LTA does. iTie deficiency gives rise to uncontrolled GSDMD activation and pyroptosis of small intestinal enterocytes. Inhibition of GSDMD permeabilization on cell membrane ameliorates the damage caused by iTie deficiency. iTes expression is diminished in small intestines of patients with Crohns disease. Our results uncover a self-control system for mouse intestine to tolerate commensal bacteria which might shed new light on the treatment of bowel diseases.

immunology↗

bioRxiv2020

Single-cell landscape of immunological responses in COVID-19 patients

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.

immunology↗

bioRxiv2020

Fast in vivo 23Na imaging and T2* mapping using accelerated 2D-FID magnetic resonance spectroscopic imaging at 3 T: Proof of concept and reliability study

PurposeTo implement an accelerated MR-acquisition method allowing to map sodium T2* relaxation and absolute concentration within skeletal muscles at 3T. MethodsA fast-2D density-weighted concentric-ring-trajectory 23Na-MRSI technique was used to acquire 64 time-points of FID with a spectral bandwidth of 312.5 Hz from a 2.5 x 2.5 mm2 in-plane resolution within about 15 minutes. The fast relaxing 23Na signal was localized with a single-shot, inversion-recovery based, non-echo (SIRENE) OVS method. The sequence was verified using simulation and phantom studies before implementing it in human calf muscles. Within two same-day sessions, 2D-SIRENE-MRSI (UTE = 0.55 ms) and 3D-MRI (UTE = 0.3 ms) data were acquired. The T2* values were fitted voxel-by-voxel using a bi-exponential model for the 2D-MRSI data. Within-subject coefficients of variation were estimated for both acquisition methods. ResultsThe MRSI-FID data allowed for fast and slow T2* mapping of the calf muscles in vivo with minimal sensitivity reduction. The spatial-distributions of 23Na concentration for both in vivo MRSI and 3D-MRI acquisitions were significantly correlated (r = 0.7, P<0.001). The test-retest results rendered high reliability for both MRSI (CV = 5%) and 3D MRI (CV = 6%). The mean [Formula] in calf muscles was 0.7 {+/-} 0.1 (contribution fraction = 37%), while [Formula] was 13.2 {+/-} 0.2 ms (63%). The mean absolute muscle 23Na concentration calculated from the T2*-corrected data was 28.6 {+/-} 3.3 mM. ConclusionThe proposed MRSI technique is a reliable technique to map sodiums absolute concentration and T2* within a clinically acceptable scan time at 3T.

biophysics↗

bioRxiv2020

A novel full-reduced HMGB1 and kartogenin-containing bio-active scaffold for meniscus regeneration

A novel bio-active scaffold for enhancing wounded meniscus healing has been developed by combination of High mobility group box 1 protein (HMGB1) and kartogenin (KGN) with alginate gel. The properties of the bio-active scaffold were also investigated using an in vitro cell culture model and in vivo rat wounded meniscus healing model. This HMGB1-KGN-containing bioactive scaffold released HMGB1 and KGN into wound area and kept high concentrations of HMGB1 and KGN in the system for more than two weeks. This HMGB1-KGN-containing bioactive scaffold also activated rat bone marrow stem cells (BMSCs) from G0 to GAlert stage and promoted cell proliferation as evidenced by 5-bromo-2-deoxyuridine (BrdU) incorporation testing. Our results also demonstrated that the HMGB1-KGN-containing bioactive scaffold induced cell migration in vitro and recruited the cells to wound area to promote wounded rat meniscus healing in vivo.

bioengineering↗

bioRxiv2020

Sapphire Nanopores for Low-Noise DNA Sensing

Silicon-supported (SiS) solid-state nanopores have broad applications in single-molecule biosensing and diagnostics, but their high capacitive noise has seriously limited both their sensing accuracy and recording speed. Nanopores on insulating glass have demonstrated reduced capacitance and noise, but it remains challenging to bulk-etch amorphous glass to create membranes reproducibly and uniformly. Here a new approach is reported to form triangular sapphire-supported (SaS) nanopore membranes by batch-processing-compatible anisotropic wet etching of sapphire, with membrane dimension demonstrated from ~200 μm to 5 μm. A SaS nanopore in 68 μm-wide silicon nitride membrane has 130 times smaller capacitance (10 pF) compared to a SiS nanopore (~4 μm SiN membrane, ~1.3 nF), despite a 100 times larger membrane. It has a current noise of 18 pA over 100 kHz bandwidth, much smaller than that from our SiS nanopore (46 pA) and comparable with the best reported low-noise nanopores. Further, the SaS nanopore displays a higher signal-to-noise ratio (SNR, 21 versus 11 for SiS nanopore) in DNA sensing, although the SNR can be further improved using thinner membranes and smaller pores. The SaS nanopore presents a simple platform in both fabrication and structure that is particularly suitable for low-noise and high-speed molecular diagnostics.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2019

Single-cell RNA-seq data reveals TNBC tumor heterogeneity through characterizing subclone compositions and proportions

Understanding subclonal architecture and their biological functions poses one of the key challenges to deeply portray and investigative the cause of triple-negative breast cancer (TNBC). Here we combine single-cell and bulk sequencing data to analyze tumor heterogeneity through characterizing subclone compositions and proportions. Based on sing-cell RNA-seq data (GSE118389) we identified five distinct cell subpopulations and characterized their biological functions based on their gene markers. According to the results of functional annotation, we found that C1 and C2 are related to immune functions, while C5 is related to programmed cell death. Then based on subclonal basis gene expression matrix, we applied deconvolution algorithm on TCGA tissue RNA-seq data and observed that microenvironment is diverse among TNBC subclones, especially C1 is closely related to T cells. Whats more, we also found that high C5 proportions would led to poor survival outcome, log-rank test p-value and HR [95%CI] for five years overall survival in GSE96058 dataset were 0.0158 and 2.557 [1.160-5.636]. Collectively, our analysis reveals both intra-tumor and inter-tumor heterogeneity and their association with subclonal microenvironment in TNBC (subclone compositions and proportions), and uncovers the organic combination of subclones dictating poor outcomes in this disease. HighlightsWe applied deconvolution algorithm on subclonal basis gene expression matrix to link single cells and bulk tissue together.

cancer biology↗

bioRxiv2019

An adhesion code ensures robust pattern formation during tissue morphogenesis

An outstanding question in embryo development is how spatial patterns are formed robustly. In the zebrafish spinal cord, neural progenitors form stereotypic stripe-like patterns despite noisy morphogen signaling and large-scale cellular rearrangement required for tissue growth and morphogenesis. We set out to understand the mechanisms underlying this patterning robustness. Our adhesion assays revealed a preference for three neural progenitor types to stabilize contacts with cells of the same type. Genetic analysis uncovered a three-molecule adhesion code, composed of N-cadherin, Cadherin 11, and Protocadherin 19, with unique gene expression profiles for each cell type. Perturbation of the adhesion code results in loss of homotypic preference ex vivo and patterning errors in vivo. Both the cell fate and adhesion code are co-regulated by the common upstream morphogen signal Shh. We propose that robust patterning in tissues undergoing morphogenesis results from a previously unappreciated interplay between morphogen gradient-based patterning and adhesion-based self-organization.

developmental biology↗

bioRxiv2019

Musculoskeletal fat imaging and quantification by high-resolution metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A fast method to generate separate distribution maps of lipid components

PurposeTo provide a rapid, non-invasive fat quantification technique capable of producing separate lipid component maps.\n\nMethodsThe calf muscles in 5 healthy adolescents (age 12-16 years; BMI = 20 {+/-} 3 Kg/m2) were scanned by two different fat fraction (FF) quantification methods. A high-resolution, density-weighted concentric ring trajectory (DW-CRT) metabolite cycling (MC) magnetic resonance spectroscopic imaging (MRSI) technique was implemented to collect data with 0.25 mL resolution within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity (SSIM) analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data.\n\nResultsThe proposed MRSI technique provided individual FF maps for eight musculoskeletal lipids identified by LCModel analysis (L09, L11, L13, L15, L21, L23, L53, and L55) with mean SSIM indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively compared to that of Dixons FF map. Further analysis of voxels with zero SSIM demonstrated an increased sensitivity of FF lipid maps from data acquired using this MRSI technique over the standard Dixon technique. The trend of lipid spatial distribution over calf muscles was consistent with previously published findings in adults.\n\nConclusionThe advantages of this MRSI technique make it a useful tool when individual lipid FF maps are desired within a short scanning time.

biochemistry↗

bioRxiv2019

Density-Weighted Concentric Ring Trajectory using simultaneous multi-band acceleration: 3D Metabolite-cycled Magnetic Resonance Spectroscopy Imaging at 3 T

Simultaneous multi-slice or multi-band parallel imaging is frequently used in fMRI to accelerate acquisition. In this study, we propose a new a non-water-suppressed multi-band MRSI using a density weighted concentric ring trajectory (DW-CRT) acquisition. The properties of multi-band acquisition scheme were compared against single-band acquisition in phantoms and in-vivo experiments. High-quality spectra were acquired for all simultaneously acquired three slices from a limited volume of interest with an in-plane resolution of 5 x 5 mm2 in 19.2 min. The achieved in vivo spectral quality of the multi-band method allowed the reliable metabolic mapping of four major metabolites with Cramer-Rao lower bounds below 50%, using a LCModel analysis. Metabolite maps and LCModel quality metrics were compared between multi-band and single-band acquisition schemes for both phantom and in-vivo measurements. Structural similarity (SSIM) index and conventional coefficient of variance analysis of both phantom and in-vivo measurements revealed a SSIM index higher than 0.83, corresponding to a coefficient of variance of less than 30%. These findings demonstrate that our multi-band DW-CRT MRSI demonstrate a multi-band acceleration, simultaneously acquired 3 slices, with no apparently loss in spectral quality, reducing scan time by a factor of 3 without any significant penalty.

neuroscience↗