Biomedical subjects

Qi Liu

Publications and source records attributed to Qi Liu.

17 recordsLinked to original sources

PubMed2026

Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis.

Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single-cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single-cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC-related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand-receptor expression patterns and ligand-associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single-cell-derived inflammatory and remodeling signatures were represented at the tissue-transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine-response, and stress-response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll-like receptor signaling, and inflammasome-associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+ synthetic VSMCs, KRT7+ VSMC-like cells, interferon-responsive VSMCs, pericyte-like mural cells, and osteogenic/modulated VSMCs. Pseudotime analysis showed a broad contractile-to-osteogenic/modulated transcriptional continuum accompanied by increased expression of remodeling-associated genes and selected inflammatory or remodeling-associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand-receptor and ligand-associated target gene expression patterns involving SPP1-CD44, TNF-TNFRSF1A, IL1B-IL1R1/IL1RAP, MIF-ACKR3, PDGFB-PDGFRB, and FN1-SDC1/ITGB1. In GSE28829, inflammatory macrophage-, osteogenic/modulated VSMC-, candidate ligand-receptor expression-, SPP1-CD44 candidate axis-, and NicheNet-prioritized target program-related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrative transcriptomic analysis identified a highly inflammatory macrophage state and a VSMC remodeling continuum in human atherosclerotic plaques. Candidate ligand-receptor and ligand-associated target gene expression patterns linked inflammatory macrophage activation with osteogenic/modulated VSMC remodeling at the computational level. External bulk data further showed coordinated enrichment of inflammatory and remodeling signatures in advanced plaques. These findings provide a descriptive and hypothesis-generating transcriptomic framework for understanding inflammatory macrophage activation and VSMC remodeling in human atherosclerosis.

atherosclerosis↗

PubMed2026

Author Correction: Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.

Explore the source record for details and available documents.

Published Erratum↗

PubMed2026

FMRP promotes gastric cancer progression via m6A-dependent stabilization of DVL2 and activation of the Wnt/PCP-JNK pathway.

BACKGROUND: N6-methyladenosine (m6A) modification has emerged as a critical regulator in gastric cancer progression. Fragile X messenger ribonucleoprotein 1 (FMRP), an RNA-binding protein with tumorigenic potential, remains poorly characterized in gastric cancer. METHODS: FMRP expression in gastric cancer was assessed through bioinformatic analyses and tissue microarray-based immunohistochemistry. Its biological functions were examined through loss-of-function experiments in vitro and in vivo. Mechanistic investigations, including RNA interaction, m6A site mutation, and RNA stability analyses, were performed to identify downstream targets and pathways regulated by FMRP. RESULTS: Bioinformatic analyses and tissue microarray-based immunohistochemistry showed that FMRP was significantly upregulated in gastric cancer tissues. FMRP depletion suppressed tumor growth and metastasis. Subsequently, Dishevelled segment polarity protein 2 (DVL2) was identified as a candidate downstream target of FMRP. DVL2 was also significantly upregulated in gastric cancer tissues, and its expression positively correlated with FMRP expression. Mechanistically, FMRP bound to DVL2 mRNA and enhanced its stability in an m6A-dependent manner. Among the candidate sites tested, mutation of 1271A attenuated FMRP-mediated regulation of DVL2 reporter activity, supporting the involvement of this site. Functionally, FMRP promoted activation of the noncanonical Wnt/planar cell polarity (PCP) signaling pathway and enhanced the proliferative, migratory, and invasive capacities of gastric cancer cells via DVL2. CONCLUSIONS: These results define FMRP as an oncogenic driver in gastric cancer that operates via the DVL2/Wnt/PCP axis. Targeting this pathway may provide a potential therapeutic strategy for gastric cancer.

Stomach Neoplasms↗

PubMed2026

MARK1 suppresses infectious bursal disease virus replication via phosphorylating VP3.

Infectious bursal disease virus (IBDV) of the Birnaviridae family is a non-envelope, double-stranded RNA virus that encodes a VP3 protein with multiple functions, which controls viral genome replication, IFN-β production, and virus traffic in infected cells. Posttranslational modifications (PTMs), such as ubiquitination, of VP3 have been demonstrated for affecting its function and stability. To clarify the mechanism by which VP3 is regulated in IBDV infected cells, we focused on the phosphorylation of VP3. Mass spectrometry analysis identified that microtubule-affinity regulating kinases 1 (MARK1) was a kinase interacting protein of VP3. Inhibitory function of MARK1 in affecting viral replication was validated. We describe the phosphorylation event at the serine 130 (S130) and serine 163 (S163) residues of VP3 mediated by MARK1 via mass spectrometry analysis. Alanine replacement of the phosphorylation sites in VP3 significantly enhanced its RNA-binding activity. Additionally, the mutation of two serine residues led to remarkably improved in its polymerase-enhancing function. We then incorporated the two mutations to rescue recombinant IBDV. Viral growth curve analysis revealed that replication of mutant IBDV was significantly enhanced relative to wild type (WT) virus. In conclusion, we found that VP3 functions are specifically regulated by MARK1 mediated phosphorylation at S130 and S163 and that this regulation suppresses IBDV replication ultimately.

Infectious bursal disease virus↗

PubMed2026

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8 days to four thermal regimes: constant 18 °C (CT), constant 28 °C (HT), intermittent cooling from 18 to 8 °C followed by recovery to 18 °C (FL), and intermittent warming from 18 to 28 °C followed by recovery to 18 °C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P < 0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals↗

PubMed2026

Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.

Hematopoietic stem cell (HSCs) aging is a complex biological process driven by both cell-intrinsic alterations and extrinsic cues from the bone marrow niche. Understanding these mechanisms is critical for developing therapies against aging-related hematopoietic disorders. This review synthesizes recent advances in the molecular mechanisms underlying HSCs aging, including microenvironmental aging, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, and aberrant nuclear mechanotransduction. We summarize that the functional decline of HSCs during aging drives a compensatory expansion of the phenotypically defined stem cell pool, leading to an aberrant increase in cell number. We also highlight aging-associated HSCs heterogeneity, including CD150high and P-selectin-positive subsets that enrich for myeloid-biased or functionally compromised HSCs states while emphasizing that surface phenotype alone may not fully indicate functional rejuvenation. Finally, we discuss emerging rejuvenation strategies-including targeting myeloid-biased HSCs, modulating inflammatory pathways, and implementing epigenetic or metabolic interventions-supported by cutting-edge technologies such as single-cell multi-omics, gene editing, and computational modeling. These approaches hold promise for counteracting age-related hematopoietic decline and restoring immune competence.

Humans↗

PubMed2026

Enhancing pan-cancer spatial transcriptomics at single-cell resolution with stPainter.

Subcellular spatial transcriptomics can resolve tissue architecture at cellular scale, but sparse gene panels and limited detection sensitivity constrain downstream analysis. Existing enhancement methods often require tissue-matched single-cell RNA sequencing (scRNA-seq) references and dataset-specific retraining. Here we show that stPainter, a conditional generative model pretrained on a pan-cancer scRNA-seq atlas, can enhance spatial transcriptomics data without matched references or retraining. Using a latent diffusion architecture guided by Stochastic Differential Equations (SDE), stPainter reconstructs expanded expression profiles from sparse measurements and produces latent representations for clustering and cell-state analysis. When we apply stPainter upon 6 spatial transcriptomics datasets of different cancer types, we demonstrate that our model empowers downstream biological analyses, including fine-grained subpopulation clustering and pathway enrichment. Comparison with spatially resolved proteomics (CODEX) provided independent support for regional agreement between imputed cellular compositions and protein-level tissue organization. These results establish stPainter as a scalable approach for analyzing tumor microenvironments without auxiliary sequencing data.

Spatial Transcriptomics↗

PubMed2026

Metabolic-cell-death gene trio predicts survival and cuproptosis sensitivity in colorectal cancer.

BACKGROUND: Metabolic cell death (MCD) modulates colorectal cancer (CRC) progression, yet its prognostic value remains unexplored. We aimed to build an MCD-centred gene signature for outcome prediction and precision therapy. METHODS: Transcriptomes of 1,174 CRC patients were integrated. Weighted gene co-expression network analysis, differential expressions and least absolute shrinkage and selection operator (LASSO) + random survival forest were successively applied to derive a three-gene (CDKN2A/MPC1/AHCY) risk model. Functional, immune-infiltration, drug-sensitivity and genomic analyses were performed, followed by validation in fresh clinical specimens and cell lines. RESULTS: Integrative metabolic-death transcriptomics identified CDKN2A, MPC1 and AHCY as the hub drivers of CRC. Their three-gene signature robustly stratified patients into high- and low-risk subsets [3-year area under the curve (AUC) 0.83-0.85, P<0.001]. High-risk tumors were enriched for extracellular matrix (ECM)-receptor-interaction pathways, displayed abundant myeloid-derived suppressor cell (MDSC) infiltration and were more vulnerable to AZD8186, AZ960 and JAK inhibitors. Guided by these in-silico findings, we functionally confirmed that CDKN2A silencing markedly repressed proliferation, invasion and migration of SW480/HCT116 cells and potentiated cuproptosis via up-regulation of lipoylated DLAT/DLST and CTR1. CONCLUSIONS: We report the first MCD-derived prognostic platform for CRC that simultaneously predicts survival and therapeutic response. Targeting CDKN2A-enhanced cuproptosis represents a promising metabolic-precision strategy for high-risk patients.

Colorectal cancer (CRC)↗

PubMed2026

Comparative analysis of histological and transcriptomic characteristics in caudal muscles of nile crocodiles (Crocodylus niloticus), siamese crocodiles (Crocodylus siamensis), and their hybrids.

Crocodylus niloticus and Crocodylus siamensis are high-value aquaculture species. C. niloticus is large-bodied but less abundant, while C. siamensis grows fast but is small-sized. Their hybrids combine parental advantages, yet relevant research is scarce. This study compared the histological and transcriptomic characteristics of the caudal muscle across the three taxa. HE staining indicated that C. niloticus had significantly larger myofiber diameters (p < 0.05); C. siamensis had the smallest, and the myofiber density of hybrids was much closer to that of C. siamensis. Masson's trichrome staining indicated that C. niloticus had the thickest collagen fibers (p < 0.05), C. siamensis the thinnest, and hybrids exhibited highly similar histological traits to C. siamensis. C. niloticus had higher LDH and SDH activities in caudal muscles, whereas the hybrid crocodile indicated the highest CK activity. Transcriptomic analysis identified numerous differentially expressed genes (DEGs), which were enriched in growth, muscle metabolism, and energy allocation pathways via GO/KEGG annotations. PPI analysis screened 24 hub genes related to energy metabolism. This study systematically reveals caudal muscle differences, providing insights into growth-related molecular mechanisms and theoretical support for crocodile artificial breeding.

Animals↗

PubMed2026

Alternative End Joining Dependency Imposed by miR-21-5p Defines Radiation Resistance and a Targetable Vulnerability in Oral Squamous Cell Carcinoma.

PURPOSE: Clinical control of oral squamous cell carcinoma (OSCC) is constrained by heterogeneous radiosensitivity driven by divergent DNA damage response programs. The architecture and functional contribution of alternative end joining (Alt-EJ), an error-prone DNA double-strand break (DSB) repair pathway frequently upregulated in cancer, to radiation resistance remains poorly defined. METHODS AND MATERIALS: We profiled microRNAs in radioresistant OSCC clones and performed multiomic integration across an institutional OSCC cohort, an external OSCC cohort from the Gene Expression Omnibus, The Cancer Genome Atlas pan-cancer tumors, and cell lines characterized by Sanger Genomics of Drug Sensitivity in Cancer to infer DNA damage response characteristics, genomic scar features, drug sensitivity, and radiation therapy outcomes. DSB repair capacity and pathway usage were validated using functional assays, including Alt-EJ reporters and droplet digital PCR quantification of microhomology-mediated repair events. Core Alt-EJ effectors such as PARP1 and POLQ were perturbed genetically and pharmacologically. Therapeutic efficacy of PARP or POLQ inhibition with or without irradiation was tested in a syngeneic OSCC model, followed by bulk tumor transcriptomics to assess pathway engagement. RESULTS: Upregulation of miR-21-5p was not only selectively detected in radioresistant OSCC, but also modulated radiosensitivity in vitro and in vivo, and was associated with inferior postradiation therapy survival. A calibrated miR-21-5p target-gene signature tracked Alt-EJ activity across patient and mouse tumors and cancer cell lines, correlated with microhomology-mediated indels and broader genomic scarring, and predicted sensitivity to clinically available PARP inhibitors. Functionally, enforced miR-21-5p expression increased Alt-EJ usage and accelerated DSB repair, whereas inhibition or depletion of key Alt-EJ effectors reduced repair efficiency and restored radiosensitivity. In vivo, Alt-EJ targeting with PARP or POLQ inhibitor abrogated miR-21-5p-driven radiation resistance; transcriptomic profiling supported suppression of Alt-EJ programs as the operative mechanism. CONCLUSIONS: These findings establish a mechanistic link between miR-21-5p activity and Alt-EJ dependence, provide a clinically deployable signature to identify Alt-EJ-dependent OSCC, and support rational combinations of Alt-EJ targeting agents with radiation therapy to overcome treatment failure and advance precision radiation oncology.

MicroRNAs↗

PubMed2025

Multi-ancestry genome-wide and transcriptome-wide association analyses identified new risk loci and genes for inflammatory bowel disease.

To advance genetic understanding of inflammatory bowel disease (IBD), we conducted genome-wide association meta-analyses of 63,415 IBD cases of European and East Asian descendants and identified 90 previously unknown risk loci. Integrating multi-ancestry transcriptome-wide association studies (TWAS), cell type-specific TWAS, alternative splicing (AS-WAS), and alternative polyadenylation (APA-WAS) analyses using RNA-seq data from normal colon tissues of 707 European and 364 East Asian individuals, we uncovered 506 high-confidence IBD risk genes, including 384 not previously reported. These genes converge on immune regulation, microbial interaction, and other pathways central to IBD pathogenesis, with over half showing transcriptional dysregulation supported by single-cell and spatial omics analyses. Notably, 46 risk genes are targeted by 225 drugs that have been approved or in Phase II/III trials, including sulfasalazine already used in IBD therapy. Our study findings deepen the understanding of IBD genetics and support the development of precision medicine for its prevention and treatment.

GWAS↗

PubMed2025

In vivo genome-wide CRISPR screens in human T cells to enhance T cell therapy for solid tumors.

Large-scale CRISPR screening in human T cells holds significant promise for identifying genetic modifications that can enhance cellular immunotherapy. However, many genetic regulators of T cell performance in solid tumors may not be readily revealed in vitro. In vivo screening in tumor-bearing mice offers greater physiological relevance, but has historically been limited by low intratumoral T cell recovery. Here, we developed a new model system that achieves significantly higher human T cell recovery from tumors, enabling genome-wide in vivo screens with small numbers of mice. Tumor-infiltrating T cells in this model exhibit hallmarks of dysfunction compared to matched splenic T cells, creating an ideal context for screening for genetic modifiers of T cell activity in the tumor microenvironment. Using this platform, we performed two genome-wide CRISPR knockout screens to identify genes regulating T cell intratumoral abundance and effector function (e.g., IFN-γ production). The intratumoral abundance screen uncovered the P2RY8-Gα13 GPCR signaling pathway as a negative regulator of human T cell infiltration into tumors. The effector function screen identified GNAS (Gαs), a central signaling mediator downstream of multiple GPCRs that sense different suppressive ligands, as a key regulator of T cell dysfunction in tumors. Targeted GNAS knockout rendered T cells resistant to multiple suppressive cues and significantly improved therapeutic performance across diverse solid tumor models. Moreover, combinatorial knockout of P2RY8 (trafficking) and GNAS (effector function) further enhanced overall tumor control, demonstrating that genetic modifications targeting distinct T cell phenotypes can be combined to improve therapeutic potency. This flexible and scalable in vivo screening platform can be adapted to diverse tumor models and pooled CRISPR libraries, enabling future discovery of genetic strategies that equip T cell therapies to overcome barriers imposed by solid tumors.

Journal Article↗

PubMed2025

A comprehensive analysis of supermere, exomere, and extracellular vesicle isolation and cargo in colorectal cancer.

Biofluids contain a heterogeneous mixture of extracellular vesicles and non-vesicular nanoparticles (including exomeres and supermeres) that transport a diverse array of proteins, RNA, and lipids. Our previous efforts to characterize the contents of these carriers in colorectal cancer relied on 2D culture systems requiring large-scale setups and time-consuming ultracentrifugation-based isolation. To streamline this process, we have combined 3D hollow-fiber bioreactor production and fast-protein liquid chromatography-based size-exclusion chromatography. Here, we compare the impact of culture methods and purification strategies on small extracellular vesicle, exomere, and supermere cargo. Proteomic analyses show consistently distinct profiles for extracellular vesicles, exomeres, and supermeres regardless of culture conditions or isolation method. In contrast, these two variables influence small RNAs, their base modifications, and lipidomic profiles. We present an online tool to query these and future secretome datasets (https://superomics.shinyapps.io/browse).

Humans↗

PubMed2025

Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.

In the tumour microenvironment, accumulated lactic acid (LA) promotes tumour immune evasion by facilitating regulatory T cell (Treg) immunosuppressive function and restraining CD8+ T cell cytotoxicity, but the underlying mechanism remains elusive. Here we report that transcriptional factor MondoA-induced thioredoxin interacting protein (TXNIP) transcription is a common feature of both Treg and CD8+ T cells in response to lactic acid. In contrast to reduction in immunosuppressive capacity in MondoA-deficient Treg cells, loss of MondoA enhanced CD8+ T cell cytotoxic function in the lactic-acid-induced immunosuppressive microenvironment, by restoring glucose uptake and glycolysis. Mechanistically, lactic acid relied on sentrin/SUMO-specific protease 1 (SENP1) to stimulate the MondoA-TXNIP axis, which impaired TCR/CD28-signal-induced CD8+ T cell activation. Importantly, targeting the MondoA-TXNIP axis potentiated antitumour immunity in multiple cancer types and synergized with anti-PD-1 therapy to promote effective T cell responses in colorectal cancer. Our results demonstrate that the MondoA-TXNIP axis is a promising therapeutic target for improving cancer immunotherapy.

Tumor Microenvironment↗

PubMed2025

MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.

BACKGROUND/OBJECTIVES: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to impair SWI/SNF function. This single genetic lesion leads to a cascade of events that promote tumorigenesis, some of which may involve the intersection of SWI/SNF with oncogenic pathways such as those regulated by the MYC oncogene. In SCCOHT tumors and other cancers marked by SWI/SNF subunit mutation, MYC target genes are recurrently activated, pointing to a relationship between SWI/SNF and MYC that has yet to be fully explored. METHODS: In this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data. RESULTS: We find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5. CONCLUSIONS: Collectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC.

ATR↗

PubMed2025

Clinical characteristic of isolated thrombocytopenia in patients with bone marrow failure-related germline variants: a retrospective study from a single centre.

BACKGROUND: Immune thrombocytopenia (ITP) comprises the majority of thrombocytopenia. Some patients respond poorly to first-line ITP therapy or develop pancytopenia years later. Recent studies link heterozygous germline variants in acquired aplastic anemia (AA), yet their role in isolated thrombocytopenia carrying bone marrow failure-related germline variants (ITGV-BMFs) remains unclear. While whole-exome sequencing (WES) detects these variants, its cost limits routine use. This study compares prognosis and clinical features of isolated thrombocytopenia in patients with ITGV-BMFsand those with classic ITP. METHODS: The clinical data of patients diagnosed with ITGV-BMFs were retrospectively analyzed and compared with those of patients with classic ITP from August 2018 to February 2024. The baseline characteristics, genomic systematically background, previous treatment response as well as their follow-up outcomes were compared. RESULTS: Patients with ITGV-BMFs demonstrated earlier onset age (p < 0.001), lower bleeding scores and CD34%, along with elevated mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and reticulocyte (RET) counts (p < 0.001). Multivariate logistic regression analysis showed that the patients with ITGV-BMFs may possess distinct characteristics, including an earlier age at onset (p = 0.014) and lower bleeding score (p = 0.048). Notably, MCV and RET showed promising performance in receiver operating characteristic (ROC) curve analysis. During the follow-up period, 57.69% (15/26) ITGV-BMFs patients were further confirmed as aplastic anemia (AA, n = 13) or myelodysplastic syndrome (MDS, n = 2), with a median progression-free survival (PFS) of 7.25 years (p < 0.0001). CONCLUSION: ITGV-BMFs may be diagnosed early using elevated MCV and reticulocyte counts, a diagnostic approach that may lead to earlier intervention and improved prognosis.

Humans↗

PubMed2025

Beyond parental lines: multi-omics analyses reveal epigenetic and transcriptional mechanisms underlying heterosis in Oryza sativa × Oryza rufipogon hybrids.

Heterosis, or hybrid vigor, refers to the superior phenotypes of a hybrid compared with their parents and is widely exploited in agriculture. Interspecific hybrids within the Oryza genus demonstrate significant potential for the systematic improvement of rice varieties. Nevertheless, the mechanistic basis underlying heterosis in interspecific Oryza hybrids remains poorly understood. Here, we systematically performed phenotypic characterization, whole-genome bisulfite sequencing, RNA sequencing, and small RNA profiling using Oryza sativa L. ssp. japonica cv. Nipponbare (NIP), Oryza rufipogon Griff. acc. CWR, and their resulting F1 hybrid (named as NC). NIP and CWR showed distinct phenotypic and molecular differences. The interspecific hybrid, NC, exhibited significant yield heterosis. In the hybrid, most epigenetic and transcriptional features displayed additive inheritance patterns relative to parental lines. Analysis revealed that domestication-selected genes maintained relatively low DNA methylation coupled with high expression levels in both hybrid and parental lines. Additionally, we identified that non-additive miRNAs were potentially involved in regulating fertility, cell growth, and cell division processes in the hybrid. A significant negative correlation was observed between DNA methylation level and gene expression. Functional enrichment analysis revealed that hybrid-MPV DEGs were significantly associated with flowering time regulation, carbohydrate metabolism, photosynthesis, protein phosphorylation, seed development, and defense responses. Through weighted gene co-expression network analysis, we identified 102 functional gene modules, six of which were significantly associated with yield-related heterosis. Collectively, our results provide a multi-omics framework for understanding interspecific hybridization between elite cultivars and wild rice relatives, highlighting CWR as an untapped genetic reservoir for rice improvement.

Oryza↗