Biomedical subjects

Li Wang

Publications and source records attributed to Li Wang.

At least 19 recordsLinked to original sources

PubMed2026

The N6-methyladenosine reader IGF2BP2 in T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous and aggressive lymphoid neoplasm that lacks pathogenic biomarkers of RNA modification with therapeutic potential. IGF2BP2 is recognized as an N6-methyladenosine reader critically involved in oncogenesis. In this study, we observed consistently high expression of IGF2BP2 across common nodal PTCL subtypes in 3 independent external cohorts, which was further confirmed in our RNA-sequencing (RNA-seq) data set of 196 patients with newly diagnosed PTCL. Both in vitro and in vivo, IGF2BP2 promoted tumor cell growth and inhibited CD8+ T-cell infiltration within the tumor microenvironment. Mechanistically, IGF2BP2 bound to endosome-related genes (RAB4, VPS35, RAB9, and STAM) to maintain their stability, which resulted in enhanced endocytic activity and increased internalization of membrane proteins, and ultimately induced tumor cell proliferation and inhibition of CD8+ T-cell-mediated tumor cytotoxicity. The relationship between IGF2BP2 and endocytosis-associated genes was confirmed using RNA-seq data from patients with PTCL. IGF2BP2 as an upstream regulator of both tumor growth and immune suppression was further demonstrated in patient-derived xenograft models and a coculture system established using tumor samples from patients with PTCL and peripheral blood mononuclear cells. Notably, therapeutic targeting of IGF2BP2 with CWI1-2 suppressed endocytosis and impeded tumor growth in both cell lines and patient-derived xenograft models. Collectively, our findings highlight IGF2BP2 as a clinically relevant oncogenic driver in PTCL that integrates tumor-intrinsic growth signals with immune evasion through endocytosis-centered regulation, providing a novel therapeutic rationale for RNA modification-based strategies that concurrently target tumor cells and the tumor microenvironment.

Humans↗

PubMed2026

PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer is characterized by redox adaptation and metabolic plasticity, but the mechanisms linking these processes remain incompletely understood. Integrating bulk, single-cell, and spatial transcriptomic analyses, we identified PRDX1 as a malignant epithelial cell-associated factor linked to adverse outcome. Genetic gain- and loss-of-function studies showed that PRDX1 promoted proliferation, motility, and xenograft growth while limiting reactive oxygen species accumulation and mitochondrial apoptosis. Proteomic and biochemical analyses identified an association between PRDX1 and SCD1. PRDX1 prolonged the SCD1 protein half-life without detectably altering SCD1 transcript abundance and increased USP7-SCD1 co-precipitation. USP7 removed K48-linked polyubiquitin chains from SCD1 and prevented its proteasomal degradation, whereas catalytically inactive USP7 failed to deubiquitinate SCD1. Deletion of PRDX1 residues 157-199 weakened its association with SCD1 and reduced USP7-SCD1 co-precipitation. Depletion of SCD1 or USP7 suppressed PRDX1-dependent growth in vitro and in xenografts. These findings support a model in which PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer↗

PubMed2026

Investigating the causal effects of physical activity and sedentary behavior on hernia risk: A two-sample Mendelian randomization approach.

The global prevalence of hernia is increasing, particularly due to the aging population. Although physical activity and sedentary behavior are known to influence various health outcomes, their specific roles in hernia development remain inadequately investigated. This study aimed to systematically assess the causal relationships between physical activity, sedentary behavior, and the risk of hernia development using Mendelian randomization (MR) analysis. We used genome-wide association study data from the UK Biobank and FinnGen Biobank to explore the causal effects of sedentary behavior on hernia risk via 5 distinct MR approaches. To ensure the reliability of our risk models, we performed sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Furthermore, we employed multivariable MR analysis to determine the independent causal effects of both physical activity and sedentary behavior. Our findings indicate that moderate-to-vigorous physical activity (MVPA) was significantly associated with an increased risk of inguinal hernia, with an odds ratio of 1.844 (95% confidence interval, 1.181-2.879; P = .007). Associations between sedentary behavior and diaphragmatic or umbilical hernia were inconsistent across methods and were sensitive to pleiotropy; thus, no robust causal relationship was established. Multivariable MR analysis further confirmed the independent and significant causal relationship between MVPA and inguinal hernia, with an odds ratio of 1.901 (95% confidence interval, 1.098-3.291; P = .022). Our study highlights a significant association between MVPA and an increased risk of inguinal hernia, suggesting that physical activity should be carefully considered in preventive strategies for hernias. However, the relationship between sedentary behavior and hernia development warrants further investigation.

Mendelian Randomization Analysis↗

PubMed2026

Tumor-Infiltrating Clonal Hematopoiesis Is Associated with Adverse Clinical Outcomes in Diffuse Large B-cell Lymphoma.

UNLABELLED: Tumor-infiltrating clonal hematopoiesis (TI-CH) contributes to the progression of nonhematologic cancers. CH is prevalent in the peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), but TI-CH prevalence and clinical relevance remain largely unexplored. In this study, through genome- and exome-wide sequencing of DLBCL biopsies and blood samples from 304 treatment-naïve patients, we identified TI-CH in 13.5% of cases, which emerged as an independent risk indicator for disease progression and death. TI-CH cases had an enrichment of inflammatory myeloid signatures revealed by gene expression profiling of tumor biopsies. In addition, we developed a TI-CH-associated prognostic signature (CAPS) based on 24 differentially expressed genes. A high CAPS score correlated with poor survival across four patient cohorts and remained significant in three cohorts after adjustment for patient age, sex, International Prognostic Index score, and cell-of-origin classification. Collectively, these findings establish a link between TI-CH and clinical outcomes and implicate the inflammatory signature as the potential underlying basis. SIGNIFICANCE: TI-CH correlates with disease progression and death in patients and with the inflammatory modeling of the DLBCL tumor microenvironment. Our results underscore the clinical and biological relevance of TI-CH and suggest its potential as a biomarker for risk stratification and as a target for therapeutic intervention in DLBCL.

Humans↗

PubMed2026

3D epigenome of glial cell types in developing human cortex.

The human cortex is complex and heterogeneous, undergoing extensive expansion during development1,2. Our prior study of neurogenesis, including radial glia (RG), intermediate progenitor cells, excitatory neurons and interneurons demonstrated that chromatin looping underlies transcriptional regulation for lineage-specific genes, shedding light on how non-coding genetic variants contribute to neuropsychiatric disorders by means of cell-type-specific gene regulation3. RG have a crucial role in generating cellular diversity through both neurogenesis and gliogenesis and can be further classified into ventricular RG (vRG) and outer RG (oRG)4,5. Given their significance in cortical development, we conducted a comprehensive three-dimensional (3D) epigenomic analysis of four main glial populations, including vRG, oRG, oligodendrocyte precursor cells and microglia, from the mid-gestational human neocortex. By integrating gene expression, chromatin accessibility, DNA methylation and 3D chromatin interactions, we identified cell-type-specific candidate cis-regulatory elements (cCREs) and validated their regulatory function using transgenic mouse embryos. Using machine learning, we prioritized 112 schizophrenia risk variants within glia cCREs and further confirmed the predicted vRG enhancer disruption by the rs4449074 risk allele in vivo. Finally, oRG cCREs are enriched for human accelerated regions compared with other cCREs and a subset of human accelerated regions show activity differences from their chimpanzee orthologues that interact with genes involved in neuronal development. Our findings advance the understanding of human-specific gene regulation during corticogenesis.

Journal Article↗

PubMed2026

Attribution of PM2.5-Induced Transcriptomic Perturbation to Toxic Components.

Ambient fine particulate matter (PM2.5) is a chemically complex mixture whose health impacts are not fully captured by particle mass. Here, we developed an interpretable chemotranscriptomic framework to attribute PM2.5-induced molecular perturbations to toxicity-relevant components. PM2.5 collected from urban roadside and coastal environments was separated into whole, extractable, and unextractable fractions, characterized by LC/GC × GC-HRMS-based nontarget analysis and inductively coupled plasma mass spectrometry (ICP-MS), and evaluated using cytotoxicity testing and transcriptomic profiling in human bronchial epithelial cells. Urban PM2.5 exhibited greater cytotoxic potency per unit mass than coastal PM2.5, with extractable fractions accounting for most cytotoxic and pathway-level responses. Transcriptomics revealed distinct site-specific modes of action: urban PM2.5 preferentially induced oxidative stress, xenobiotic metabolism, and cell cycle suppression, consistent with acute, nonapoptotic injury, whereas coastal PM2.5 elicited weaker cytotoxicity but stronger interferon-mediated immune and apoptosis-related signaling. Integrating chemical abundance with pathway activity using random forest regression, SHAP interpretation, and mechanistic corroboration reduced 5,033 detected features to 444 pathway-linked candidate drivers. Fewer than 5% of features explained ∼95% of cumulative model contribution. Standard-confirmed contributors included plasticizer-related compounds, aromatic and heteroaromatic combustion products, and copper for urban PM2.5 and secondary/aged organics and nickel for coastal PM2.5. These findings support mechanism-informed prioritization of hazardous PM2.5 components beyond mass-based assessment.

Particulate Matter↗

PubMed2026

Non-invasive strategy for gastric cancer detection: Integration of cell-free DNA fragmentomics and protein biomarkers.

Gastric cancer (GC) ranks as the fifth most common cancer worldwide, however, accurate and non-invasive diagnostic modalities for GC remain limited. Cell-free DNA (cfDNA) fragmentomics has emerged as a promising tool for cancer cell detection. Here we develop a gastric cancer detection model, named GaFraD model. The GaFraD model uses four cfDNA fragmentomics features, including fragment size ratio (FSR), copy number variation (CNV), 9-bp end motif (Motif), and fragment size at transcription start sites (TF). This model achieves an area under the receiver-operating characteristic curve (AUC) of 0.970 (95% CI: 0.944 - 0.990), a sensitivity of 95.0% and a specificity of 80.9%. By combining the GaFraD model and conventional protein biomarkers CA19-9 and PG-I/PG-II, the CONFIRM model was generated. The CONFIRM model attained an AUC of 0.986 (95% CI: 0.966 - 1.000), a sensitivity of 95.0% and a specificity of 95.6% in detecting GC. Moreover, the CONFIRM model achieved remarkable performance (AUC = 0.983, sensitivity 95.6%, specificity 94.2%) in distinguishing patients with early-stage GC from controls. Our work showed the high discriminatory power in distinguishing GC patients from controls, indicating the clinical potential of using cfDNA fragmentomics combined with protein biomarkers for non-invasive GC detection. The results of the study provide a new avenue for early, accurate, and non-invasive clinical diagnosis of GC.

Cell-free DNA↗

PubMed2026

Metagenomic profiling of blood-associated microbial DNA signatures in leukemia-associated febrile neutropenia.

Febrile neutropenia (FN) is a life-threatening complication of chemotherapy, but the low microbial biomass of blood makes shotgun metagenomic profiles highly sensitive to technical background. We reanalyzed 47 publicly available patient sequencing runs representing 43 unique patient-timepoint samples from 19 SRA-labeled patients, together with 23 no-template-control (NTC) runs spanning 21 sequencing batches. To distinguish reference-catalogue content from progressively stronger evidence of patient-associated signal, we applied batch-matched NTC correction together with nested abundance thresholds and a feature-specific global NTC envelope. CheckM2 evaluated 1,013 bins; 13 met completeness ≥50% and contamination <10%, and dereplication yielded 11 draft MAG representatives. Ten representatives showed positive patient-to-control abundance excess, but only four showed recurrent support above both threefold matched-control abundance and the global NTC envelope. Functional annotations were therefore interpreted as reference-genome homologs rather than evidence of expression, phenotype, viability or bloodstream origin. Matched-control correction retained 19 read-level ARG types, but only seven subjects contributed complete longitudinal ARG-profile contrasts, limiting reliable temporal inference. The resulting run-resolved, nested evidence framework identified a subset of microbial DNA and ARG signals that remained detectable under increasingly stringent control criteria while distinguishing them from catalogue-level or background-sensitive signals. These findings support cautious reporting of patient-enriched microbial DNA and ARG signals rather than inference of a resident blood microbiome or clinical resistance phenotype.

antimicrobial resistance genes↗

PubMed2026

Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.

Mechanical force-driven signaling has emerged as a key regulator of cell-cell interactions (CCIs), which can enhance immune cell function. However, current biochemical approaches for studying CCIs offer minimal direct control over cellular bulk phenotypes, while synthetic biomaterial systems fail to mimic the dynamic complexity of cells. Here we introduce kpiCells, a biomaterial-based platform that uses a biomimetic membrane-endoplasmic architecture to enable finely tuned phenocopying of cellular states via modular mechanical, chemical and topographical inputs. We demonstrate that kpiCells can engage in physiological CCIs and reproduce critical subcellular features. In T cell systems, kpiCells enable integrated interrogation of afferent mechanosensing pathways and efferent force-exertion pathways, and support measurement of piconewton-scale forces at individual T cell antigen receptors as well as single cell-cell force fingerprints that define activation thresholds. This work establishes kpiCells as a bionic model that enables synthetic material design with the level of functional complexity approaching living cell systems.

Artificial Cells↗

PubMed2026

Decreased H3K79 acetylation and dysregulation of neurodevelopmental genes in fetal down syndrome.

BACKGROUND: Down syndrome (DS), the most prevalent chromosomal disorder caused by trisomy 21, manifests intellectual disability and cognitive dysfunction. Cumulative studies confirm epigenetic pathways including DNA methylation and non-coding RNAs drive DS pathological progression. Histone post-translational modifications (PTMs) are core epigenetic regulators of fetal brain development. However, genome-wide PTM alterations and their downstream functions in fetal DS brains remain poorly characterized, leaving a key gap in revealing epigenetic mechanisms underlying DS neurodevelopmental defects. To address this, we aimed to establish the first comprehensive landscape of histone PTMs in fetal DS cortex and investigate whether specific PTM changes contribute to aberrant neurodevelopmental gene expression. METHODS: Fetal cortexs from control and DS groups were subjected to global histone modification profiling via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We detected mono-, di-, and tri-methylation, acetylation, homocysteinylation and malonylation on all four core histones (H2A, H2B, H3, H4). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to map genomic binding profiles of H3 lysine 79 acetylation (H3K79ac). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to quantify mRNA levels of candidate neurodevelopmental genes. RESULTS: HPLC-MS/MS analysis identified 172 distinct histone PTMs in control fetal cortices and 168 PTMs in DS fetal cortical samples. Quantitative comparison of 22 quantifiable histone PTMs revealed that H3K79ac showed the most prominent reduction in DS samples, with a 34% decrease (P<0.05). Chromatin immunoprecipitation (ChIP)-seq verified specific H3K79ac occupancy at the genomic loci of three vital neurodevelopmental genes: TNFSF13B, NXPH1 and CAMK4. Correspondingly, qRT-PCR revealed aberrant transcription levels of these three genes in DS fetal cortices. CONCLUSIONS: This study establishes the first quantitative landscape of histone PTMs in in DS fetal cortical tissues. We demonstrate that depleted H3K79ac acts as a candidate epigenetic driver of DS neuropathology by disrupting the transcription of critical neurodevelopmental genes. This work reveals a novel epigenetic mechanism and a promising therapeutic target for DS-related neurodevelopmental disorders.

Down syndrome (DS)↗

PubMed2026

Subnuclear genome compartmentalization controls bivalent chromatin activity.

The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1-5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood. Here we generate high-resolution maps of genomic interactions with the lamina and speckles in cells of the neurogenic lineage isolated from mid-gestational human cortex, identifying an intimate association between subnuclear genome compartmentalization, chromatin state and transcription. During cortical neurogenesis, subnuclear genome compartmentalization is extensively remodelled, relocating hundreds of neuronal genes from the lamina to speckles, including key neurodevelopmental genes bivalent for trimethylation of histone H3 at Lys27 (H3K27me3) and Lys4 (H3K4me3). At the lamina, bivalent genes have exceptionally low expression, and relocation to speckles enhances resolution of bivalent chromatin to H3K4me3 monovalency and increases transcription more than eightfold. We further demonstrate that proximity to the nuclear periphery-not the presence of H3K27me3-maintains the lowly expressed, poised state of bivalent genes embedded in the lamina. We find that the repressive environment of the lamina is associated with spatial segregation of the transcriptional elongation machinery from the nuclear periphery. Our results establish a paradigm in which knowing the spatial location of a gene is necessary for understanding its epigenomic regulation.

Humans↗

PubMed2026

PRDX1 as a novel urinary biomarker for bladder cancer: Development of an integrated fiber optic sensing platform.

In this study, integrated proteomic and transcriptomic analyses identified peroxiredoxin 1 (PRDX1) as a novel urinary biomarker for bladder cancer (BC). PRDX1 was significantly upregulated in BC tissues and was associated with poorer overall survival. In vitro experiments further demonstrated that PRDX1 promotes malignant phenotypes of BC cells, including proliferation, migration, and invasion. Silencing PRDX1 in BC cells significantly reduced the invasiveness and proliferation ability.To address the clinical need for rapid and non-invasive detection, we developed an innovative optical fiber biosensor based on surface plasmon resonance (SPR) technology for the quantitative detection of urinary PRDX1. The biosensor exhibited excellent analytical performance, including high sensitivity (limit of detection: 0.06 ng/mL), a wide linear range (0-25 ng/mL), rapid response (∼14 s), as well as good stability and selectivity. In clinical validation involving 97 BC patients and 30 healthy controls, the biosensor demonstrated outstanding diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.91 and an overall diagnostic accuracy of 86.6%, outperforming conventional enzyme-linked immunosorbent assay (ELISA). Collectively, this study not only identifies PRDX1 as a promising biomarker for non-invasive diagnosis and prognostic evaluation of BC, but also establishes an efficient SPR-based optical fiber sensing platform, providing new insights into both clinical detection and the functional role of PRDX1 in BC progression.

Humans↗

PubMed2026

CSNK1E sustains stemlike drug persistence in diffuse large B-cell lymphoma.

Relapsed or refractory (R/R) disease occurs in up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) following first-line immunochemotherapy. However, the molecular mechanisms underlying drug persistence remain incompletely defined. In this study, we performed single-cell RNA and B-cell receptor sequencing on paired diagnostic and R/R samples from 8 patients who were either treatment-refractory or relapsed after remission, and validated our findings in 3 independent patient cohorts. We found that drug-persistent cells exhibited a transcriptional profile indicative of a less-differentiated state and adopted a memory B-cell-like program with enhanced stemlike properties, which correlated with unfavorable clinical outcomes across multiple DLBCL cohorts. Functionally, drug-persistent cells showed significantly increased in vitro clonogenicity and in vivo tumor-initiating capacity. Mechanistically, the WNT signaling regulator casein kinase 1ɛ (CSNK1E) was upregulated in these stemlike drug-persistent cells, in part through the activation of the A proliferation-inducing ligand (APRIL)-TNFRSF13B axis. Notably, CSNK1E inhibition impaired the growth and tumor-initiating capacity of drug-persistent cells and potentiated the efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based treatment, both in vitro and in vivo. Together, our study reveals the stemlike transcriptional and functional properties of drug-persistent cells, and identifies CSNK1E as a critical mediator and therapeutic vulnerability that may improve the efficacy of standard immunochemotherapy in DLBCL.

Lymphoma, Large B-Cell, Diffuse↗

PubMed2026

Expanding the human proteome with microproteins and peptideins.

A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states1-3, with major implications for biomedical science. However, a key gap in knowledge has been which ncORFs produce small microproteins or alternative protein molecules that contribute to the human proteome. Here we report the collaborative efforts of the TransCODE Consortium4 to produce a consensus landscape of protein-level evidence for ncORFs. We show that about 25% of a set of 7,264 ncORFs gives rise to detectable peptides in a large-scale analysis of 95,520 proteomics experiments. We develop an annotation framework for ncORF-encoded microproteins as human proteins and codify the new conceptual model of 'peptideins' as microproteins that have indeterminate potential as functional proteins. To probe the biological implications of peptideins, we create an evolutionary analysis approach, termed ORF relative branch length (ORBL), and determine that evolutionary constraint is common and associates with observation of ncORF-derived peptides. We then characterize a pan-essential cellular phenotype for one peptidein from the OLMALINC long non-coding RNA. Overall, we generate public research tools supported by GENCODE and PeptideAtlas and advance biomedical discovery for understudied components of the human proteome.

Humans↗

PubMed2026

Population and landscape genomics provide insights into the adaptive genetic variation and future climate-induced vulnerability of the endangered tree species Phoebe bournei.

Elucidating the genomic underpinnings of adaptive variation is highly important for the conservation, landscape application, and management of ornamental trees against the backdrop of global climate change. However, research on the genetic mechanisms underlying climate adaptation in Phoebe bournei-a near-threatened subtropical tree species endemic to China, which is endowed with exceptionally high ornamental and ecological value-remains scarce. Whole-genome resequencing was conducted on 362 individuals from 27 natural populations across the geographical range of the species. Genome-environment association analyses were employed to identify 1556 climate-associated variants and 167 candidate genes associated with temperature and precipitation variables. Through functional annotation and expression profiling, pivotal genes, including TRX-M4 and FBD1, were identified as integral to drought and heat stress responses, with adaptive alleles displaying distinct geographic frequency distributions and significant phenotypic differentiation. Divergent evolutionary trajectories were deduced among populations, with southeastern populations distinguished by elevated genetic diversity and strong signatures of local adaptation. Nevertheless, projections derived from the Risk of Non-Adaptedness and gradient forest models suggest that these southeastern populations will face substantial genomic offset under future climate scenarios, signaling heightened vulnerability and the need for prioritized conservation and management. This study provides the first genome-wide perspective into the adaptive evolution of P. bournei and offers a robust foundation for its conservation and climate-resilient management.

Journal Article↗

PubMed2026

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets↗

PubMed2026

CRISPR-Cas9-induced genetic mosaicism in three species of the microcrustacean Daphnia.

Genetic mosaicism can arise from in vivo CRISPR-Cas9 gene editing, especially in the embryos. This study evaluates the extent of genetic mosaicism resulted from CRISPR-Cas9-mediated knockout for 11 genes in the freshwater microcrustacean Daphnia magna, Daphnia pulex, and Daphnia sinensis. Based on extensive genotyping data of the asexually produced progenies of successfully edited females, we find strong evidence of mosaicism in 9 of these genes. The genotyping data also suggest that the gene editing activity can take place as early as the one-cell embryo stage and extends into the 32-cell and later stages. This study establishes genetic mosaicism as an important feature of Cas9-mediated gene editing in Daphnia.

Animals↗

PubMed2026

Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.

BACKGROUND: Bulky disease represents a clinically aggressive subset of diffuse large B-cell lymphoma (DLBCL) associated with adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on bulky disease in DLBCL. METHODS: We analyzed a cohort of 939 patients with newly diagnosed DLBCL. Using DNA (n = 934) and RNA (n = 524) sequencing, we compared oncogenic mutations and tumor microenvironment (TME) alterations based on tumor diameter, with cutoff values at 5.0 cm and 10.0 cm. Further stratification by mutations in key genes (CD58, STAT6, EBF1) correlated with tumor diameter revealed distinct transcriptomic and immunologic profiles. Subsequent single-cell RNA sequencing, guided by these mutational signatures, resolved the cellular heterogeneity within the TME. RESULTS: Integrative analysis revealed that tumor diameter correlated with increased incidence of mutations in CD58, STAT6, and EBF1; adverse genetic subtypes such as EZB-like MYC+ and TP53Mut; activation of oncogenic pathways (JAK/STAT, BCR, PI3K, and MYC); and an immunosuppressive tumor microenvironment. Notably, immune checkpoint molecules varied across the bulky stages, with CTLA-4, TIGIT, ICOS, and CD28 expression inversely correlated with tumor diameter, while CD70 and 4-1BBL expression positively correlated. Single-cell RNA sequencing further revealed mutation-specific tumor microenvironment insights. CD58-mutated tumor exhibited a profoundly immune-deserted microenvironment dominated by malignant B cells with minimal immune infiltration, whereas STAT6-mutated tumor was associated with increased fibroblasts and CD4 + T cells, particularly regulatory T cells (Treg) and Th1-like cells; EBF1-mutated tumor was characterized by increased proportions of malignant B cells. CONCLUSIONS: Collectively, our findings highlight the biological complexity of bulky disease, identifying candidate molecular targets and providing a biological framework for future therapeutic hypothesis generation in this clinically aggressive subset of DLBCL.

Humans↗