Abstract Background: Next-generation sequencing (NGS) is now routine in oncology practice, but clinicians still face uncertainty about how whole-exome sequencing (WES) compares with large targeted panels for identifying actionable alterations and guiding immunotherapy decisions. We addressed this by benchmarking these platforms within a massive clinico-genomic cohort to define their specific clinical utility. Methods: We retrospectively analyzed 37,898 tumor-normal pairs tested in a CAP/CLIA-certified laboratory: 3,360 WES tests (covering ∼20,000 genes) and 34,538 hybrid capture targeted panels (covering ∼500 cancer genes). We compared detection rates for single nucleotide variants (SNVs), copy number variants (CNVs), and rearrangements. Clinical variables, including stage and treatment history, were integrated to evaluate molecular patterns. Results: WES cases were enriched for lung adenocarcinoma, gastric, and colorectal cancers, whereas panel testing was dominated by lung adenocarcinoma, colorectal cancer, and hepatocellular carcinoma. Across all tumors, 701,119 somatic alterations were identified. WES yielded a mean of 76.7 alterations per patient and panels 12.8 per patient. Although WES covered the entire exome and detected clinically expected events such as >20% ERBB2 amplification in breast cancer and >4% ALK fusions in lung adenocarcinoma, its overall CNV and fusion detection remained clearly lower than panel, which showed much higher sensitivity due to deeper, specially targeted coverage. Mean TMBs were 6.5 muts/Mb (WES) and 8.8 muts/Mb (panel), with good agreement between platforms; overall, 17.0% of patients were TMB-High (≥10 muts/Mb). On both platforms, TMB-H was most frequent in endometrial carcinoma, lung squamous cell carcinoma, and urothelial carcinoma, while pancreatic and clear cell renal carcinomas showed very low TMB. Importantly for clinical decision making, early stage patients also harbored TMB-H tumors, indicating that potential candidates for immune checkpoint inhibitors are not restricted to advanced disease. Treatment-naïve patients had higher TMB-H rates than previously treated patients (22.5% vs 16.2%), consistent with therapy-driven clonal selection and supporting baseline TMB testing at initial diagnosis. The most frequently mutated genes were similar across platforms (TP53, EGFR, KRAS). Actionable alterations were common: 68.1% of panel cases carried at least one actionable gene. Conclusions: In this largest real world clinico-genomic cohort of Chinese cancer patients, we define the complementary utility of each platform. Whereas targeted panels excel at detecting clinically actionable alterations, WES delivers a comprehensive genomic blueprint that is well suited as a baseline for future minimal residual disease monitoring and the identification of novel biomarkers. Citation Format: Jing Hu, Minghui Wang, Junqiang Yin, Aibo Xia, Zanmei Xu, Shaohua Yuan, Yannan Zhu, Kunxu Xu, Yimin Guan, Haiyin Huang, Kai Wang. Optimizing precision oncology: A large scale clinico-genomic analysis of WES versus targeted panels in 37,898 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1985.

Abstract Post-traumatic stress disorder (PTSD) involves complex neuroimmune-synaptic crosstalk in the hippocampus. Here we show that interleukin-18 (IL-18), an extensively studied pro-inflammatory cytokine, serves a protective role against traumatic fear memory through a microglia-to-neuron signaling axis. Traumatic stress induces sustained upregulation of IL-18 in the hippocampus. Exogenous IL-18 administration attenuates fear memory, whereas blockade of IL-18 signaling exacerbates it. Mechanistically, microglial-derived IL-18 acts on neuronal IL-18R1 to restore stress-impaired synaptic plasticity and reduce perineuronal net density, thereby facilitating structural synaptic remodeling. In addition, IL-18 modulates the synaptic organization of fear memory-encoding engram cells within hippocampal ensembles. Together, these findings redefine IL-18 as a homeostatic regulator of post-trauma hippocampal synaptic function and identify the hippocampal IL-18 pathway as a potential therapeutic target for PTSD.

[This corrects the article DOI: 10.3389/fnut.2025.1632103.].

MicroRNAs (miRNAs) exert pivotal regulatory functions in cancer initiation, progression, and metastasis by regulating cell proliferation-cycle related genes. However, tumor-associated miRNAs in lung adenocarcinoma (LUAD) remains incompletely characterized. By interrogating TCGA mRNA-Seq datasets, we identified 1672 differentially expressed genes (DEGs) implicated in proliferation-cycle regulation in LUAD. A significant overrepresentation of transmembrane signal receptors, kinases, and TFs was observed among the DEGs, with primary enrichment in signaling pathways such as chemokine/cytokine, Wnt, EGF, Cadherin, and p53 cascades. Remarkably, CDK1 and E2F2 were characterized as key proliferation-cycle regulatory genes, demonstrating > fivefold transcriptional up-regulation in LUAD specimens compared to normal lung tissues (p < 0.001). Mechanistically, pharmacological CDK1 inhibition using fostamatinib or alsterpaullone reversed aberrant proliferative phenotypes in LUAD cells, demonstrating therapeutic reversibility in vitro. Concurrently, DEmiRNA and target analysis identified miR-31 as a critical regulator of CDK1/E2F2, showing elevated expression in LUAD. Collectively, our study establishes miR-31 as a novel biomarker for LUAD proliferative potential and implicates the miR-31/CDK1-E2F2 network as a promising target for disrupting LUAD progression. These findings establish a miRNA-centric precision therapeutic paradigm for effectively suppressing oncogenic proliferation in LUAD.

Brassica rapa (Br) encompasses many morphotypes and subspecies, so it is a good model with which to investigate plant diversification and subspeciation. Here, we resequenced the genomes of 1720 Br accessions and de novo assembled 11 representative telomere-to-telomere gapless genomes for seven elite subspecies that underwent intensive morphotypification and developed distinct agronomic traits valued to agriculture. We identified 6992 unknown genes, 110 complete (peri)centromeres, and five new satellites associated with Br morphotypes and subspecies and Brassica species evolution. The pangenome, built on 11 gapless and 20 published genomes, reveals structural variations and gene diversities among Br subspecies. Pangenome-wide association studies uncovered that the gene BrLH1 controls leaf-head formation. We show that structural changes have occurred in satellites, (peri)centromeres, and genes, contributing to fast subspeciation and morphotypification during the short history of Br cultivation, providing invaluable resources for Brassica breeding.

Accurate soybean field phenotyping is increasingly important for breeding. However, traditional measurement methods are labor-intensive and subjective, while UAV-based approaches are challenged by complex backgrounds and densely distributed small targets. This study first develops UAV-ZSAR to transform oblique UAV images into horizontal-view images and reconstruct plant geometry. A lightweight point-based model, Soy-MOPNet, is then proposed for fast and parallel detection of soybean seeds and stem nodes. The model incorporates the proposed SDConv, optimized hierarchical dilated convolution (HDC) principles, and PBOS to enhance adaptive feature fusion, receptive field design, and multi-branch training stability, respectively. Based on the detected keypoints, six phenotypic traits are extracted in parallel, providing comprehensive support for field phenotyping, breeding selection, and precision agricultural management.

Aim The present study aimed to assess the effect of preoperative prealbumin-bilirubin (preALBI) levels on this risk. Methods 585 patients with HCC undergoing major hepatectomy were included. Multivariable analysis was conducted to identify the prognostic factors. The predictive performance for morbidity was assessed. Results The baseline characteristic showed that patients in the high preALBI group exhibited significantly poorer liver function and showed a higher risk of intraoperative bleeding and blood transfusion. Multivariate analysis revealed that preALBI grade is an independent risk factor for overall (OR 1.517, P = 0.001) and major (OR 1.491, P = 0.015) morbidity. Moreover, the preALBI score demonstrates better predictive ability for overall and major morbidity compared to other indicators (all P < 0.05). Conclusion PALBI is a reliable predictor of postoperative morbidity in patients with HCC undergoing major hepatectomy. Incorporating PALBI into preoperative assessments could enhance risk stratification and improve patient management.

e15011 Background: Actionable gene fusions such as ALK, ROS1, and NTRK define critical therapeutic subsets across solid tumors but suffer from the needle-in-a-haystack challenge due to extreme rarity in unselected populations. We hypothesized that those fusion-driven oncogenesis imprints subtle and detectable morphological patterns on routine H&E slides. We present a novel AI framework designed not only to predict fusion status but to enable a cost-effective pre-screening funnel. Methods: We developed PathMoE-Fusion, a prototype-guided mixture-of-experts framework to identify fusion-associated signals directly from routine hematoxylin and eosin (H&E)-stained whole-slide images. The mixture-of-experts architecture enables multiple specialized subnetworks (“experts”) to selectively capture distinct histomorphological patterns, which serve as representative and interpretable prototypes for profiling characteristic phenotypes. PathMoE-Fusion was trained and validated on a pan-cancer cohort of 6,273 patients across 25+ cancer types, including 1,553 fusion-positive cases confirmed by next generation sequencing assays in a CAP/CLIA-certified laboratory (including ALK: 884; RET: 307; ROS1: 255; and NTRK: 107). Model operating points were selected to support conservative pre-screening use, prioritizing high specificity and enrichment of fusion-positive cases. External validation was conducted on independent cohorts, including the TCGA Pan-Cancer Atlas, to assess generalizability across cancer types and domains. Results: PathMoE-Fusion, demonstrated robust pre-screening performance across multiple actionable gene fusion targets, achieving AUROC values ranging from 0.84 (ROS1) to 0.94 (NTRK). Crucially, when deployed as a pre-screening tool under a conservative operating point prioritizing high specificity, the model yielded positive predictive values of 80.2% for ALK and 70.2% for NTRK, indicating marked enrichment of fusion-positive cases relative to their baseline prevalence. In TCGA validation, PathMoE-Fusion showed improved pre-screening performance, with more favorable enrichment characteristics than baseline approaches. Conclusions: PathMoE-Fusion serves as a rapid, low-cost digital enrichment biomarker that transforms the search for rare gene fusions. By prioritizing specificity, it acts as a pre-screening filter to populate a high-yield queue for confirmatory DNA/RNA sequencing. This framework maximizes the cost-effectiveness of molecular diagnostics, ensuring that sequencing resources are concentrated on patients most likely to benefit from life-extending targeted therapies.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a mitochondrial-driven metabolic disorder, yet the specific contributions of individual mitochondrial respiratory chain complexes remain poorly defined. In particular, inconsistent alterations in complexes I–V have been reported across different NAFLD models, representing a critical knowledge gap. Here, we systematically reviewed in vivo and in vitro studies to evaluate changes in mitochondrial complexes I–V during NAFLD progression. Overall, NAFLD is commonly associated with reduced complex activity, impaired mitochondrial respiration, and increased reactive oxygen species production. Notably, a subset of studies reported enhanced complex activity and respiration, suggesting context-dependent mitochondrial adaptations. This synthesis clarifies divergent findings and highlights mitochondrial respiratory complexes as dynamic and therapeutically relevant targets for future NAFLD intervention strategies.

Goji berry juice (GBJ) is a highly popular healthy drink among consumers. Rapid monitoring of the antioxidant properties of GBJ is crucial and necessary. A colorimetric sensor array (CSA) based on composite dyes was used for the rapid detection of the antioxidant properties of GBJ. High-dimensional spectral fingerprint information combined with chemometric methods was used to construct a quantitative prediction model. The effects of different preprocessing and feature screening methods on model prediction were compared. Machine learning algorithms were used to establish quantitative prediction models. The CARS-PLSR model achieved accurate quantification of total phenol, with Rp and RPD values of 0.95 and 3.18, respectively. For DPPH free radical scavenging rate, the CARS-LSSVR model had an Rp value of 0.95, an RPD value of 3.33, and an RMSEP of 0.04. The proposed method in the research provides a new idea for the rapid quality monitoring of the fermentation process of GBJ.

Ergothioneine (EGT) is an amino acid derivative with diverse biological activities, which has attracted extensive attention owing to its potential applications in pharmaceuticals, food, nutraceuticals, and cosmetics. Currently, most reports on the fermentative biosynthesis of EGT require the exogenous addition of precursors such as histidine, methionine, and cysteine, which would lead to high production costs in industrial applications.In this study, to achieve efficient production of EGT without exogenous precursor supplementation, eight combinations of EGT biosynthetic pathway genes from different biological sources were constructed and screened in Saccharomyces cerevisiae (S. cerevisiae). Meanwhile, the precursor metabolic pathways in S. cerevisiae were divided into three metabolic modules: the histidine metabolic pathway, the S-adenosylmethionine cycle, the sulfur assimilation pathway, followed by screening and combinatorial optimization of gene targets in different modules. Furthermore, using a multi-copy integration strategy coupled with knockout and complementation of histidine metabolic genes, we simultaneously overexpressed and strengthened the heterologous EGT biosynthetic pathway and the endogenous precursor metabolic pathways. The final integrated strain achieved an EGT production of 161.98 mg/L in shake-flask fermentation. In 5-L fed-batch fermentation without any precursor amino acids, the peak total titer of EGT fermented for 240 h reached 3053.3 mg/L, corresponding to a productivity of 12.72 mg/L/h. To our knowledge, both the shake-flask and bioreactor titers of this strain represent the highest reported levels for EGT production in S. cerevisiae to date. Modular tuning of precursor supply combined with enhanced multi-copy integration offers a new strategy for efficient EGT synthesis in S. cerevisiae.

tRNA-derived small RNAs (tsRNAs) or tRNA-derived fragments (tRFs) are an important class of regulatory molecules whose role in cardiac hypertrophy remains largely unknown. Here, we identified a novel tRF contributing to the regulation of cardiac hypertrophy that we termed CHAtRF (cardiac hypertrophy-associated tRF). The CHAtRF level was increased in mice and in patients with cardiac hypertrophy. CHAtRF deficiency attenuated angiotensin II (AngII)-induced cardiac hypertrophy and restored the heart function, while CHAtRF overexpression enhanced hypertrophic responses. Mechanistically, CHAtRF directly interacts with SRSF5 and blocks SRSF5 to bind with Psmg4 pre-mRNA, which mediates alternative splicing of Psmg4 pre-mRNA and promotes exon 2 skipping of Psmg4. CHAtRF-dependent alternative splicing of Psmg4 inhibits the expression of Psmg4 full-length isoform, resulting in progression of pathological hypertrophy. The ability of CHAtRF to regulate hypertrophy was confirmed in hiPSC-CMs, and CHAtRF serum levels are higher in individuals with myocardial hypertrophy or heart failure. Our findings reveal new insights into the previously unrecognized role of tsRNAs during cardiac hypertrophy, which provide potential novel therapeutic targets for pathological hypertrophy and might serve as potential biomarkers for diagnosing cardiac hypertrophy and heart failure.

Background:Chemotherapy resistance caused by paclitaxel (PTX) is a thorny issue in the treatment of non-small cell lung cancer (NSCLC). In recent years, it has been reported that PTX can induce the formation of polyploid giant cancer cells (PGCCs). Most PTX induced PGCCs would die, but there are still a few PGCCs that can generate daughter cells via neosis, which have stronger proliferative capability, further causing tumor repopulation. The transition from primitive tumor cells to the generation of daughter cells after induction with PTX is a complex biological process involving multiple mechanisms. Therefore, to further investigate this transformation process and explore the underlying mechanisms would help to overcome PTX resistance in clinic. Methods:Flow cytometry assays were used to detect the changes in PGCCs content. Immunofluorescence was used to observe the process of PTX inducing PGCCs and the production of daughter cells. Differentially expressed genes (DEGs) were identified through RNA sequencing (RNA-seq) analysis of primitive cancer cells of A549, as well as descendant PGCCs and daughter cells. Western blot, senescence-associated beta-galactosidase (SA-β-gal) staining, and xenograft models elucidated CDKN1A's role in complex biological process. Results:CDKN1A was highly expressed in descendant PGCCs and lowly expressed in primitive A549 and its daughter cells. We found that when CDKN1A was interfered with short hairpin RNAs (shRNAs) or inhibited with inhibitors, it could significantly reduce the generation of PGCCs and decrease the number of daughter cells. Our research found that CDKN1A knockdown was associated with dysregulation of AKT, ERK, autophagy markers and stemness/EMT-related proteins in this process, phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were found to be lowly expressed in PGCCs and daughter cells after CDKN1A was interfered. Low expression of CDKN1A could reduce the senescence of PGCCs too. Conclusions:A critical role for CDKN1A in PTX-induced PGCCs formation and subsequent neosis in NSCLC was identified. CDKN1A inhibition reduces PGCCs formation, suppresses neosis and enhances tumor sensitivity in vivo, thereby supporting its potential as a therapeutic target to overcome PTX resistance.

Objectives Neurodegenerative disease biomarkers are often present at low concentrations in their native matrices; thus, accurate measurements of these biomarkers rely on ultra-high-sensitivity assays. This study validated an ultrasensitive single-molecule array assay for detecting glial fibrillary acidic protein (GFAP) in human plasma and cerebrospinal fluid. Methods We report validation of an ultra-high-sensitivity Quanterix single-molecule array (SIMOA) GFAP discovery assay for GFAP detection in human plasma and cerebrospinal fluid. The assay range, accuracy and precision, detectability and reproducibility, parallelism, specificity (interference), and short-term stability were evaluated. All method validation procedures were designed and performed in accordance with the 2018 U.S. Food and Drug Administration Bioanalytical Method Validation. Results First, we determined the quantitative range of the assay to be 1.37–1000 pg/mL, with minimum required dilutions of 1:4 and 1:40 for plasma and cerebrospinal fluid samples, respectively. For stability, we found that GFAP in human plasma remained stable up to five freeze/thaw cycles and up to 23 hours at ambient temperature and 4°C. Hemolysis of up to 5% and lipemic effects up to 500 mg/dL were also evaluated, with no major impact on assay quantitation. This fit-for-purpose validation demonstrates that the following parameters met acceptance criteria, including standard calibration model, accuracy and precision, interference, detectability, and reproducibility, dilution linearity, and stability. Conclusion The results suggest that GFAP is a reliable and reproducible biomarker in human plasma and cerebrospinal fluid, and that the single-molecule array GFAP discovery assay supports high-sensitivity profiling.

Salt and cold stresses often occur together in nature and severely impact crop productivity, yet their transcriptional regulation remains poorly understood. Here, we conducted a time-series transcriptomic analysis of maize under salt, cold, and their combination at 0, 6, 12, and 24 h. Differential expression analysis revealed dynamic, condition-specific gene responses grouped into eight distinct temporal patterns. Promoter motif analysis of genes within each pattern identified 5–39 significantly enriched motifs, with over 40

Background The centromeric histone variant CENH3 is crucial for chromosome segregation and haploid induction in plants, yet its evolutionary patterns in legumes remain poorly characterized.Methods We investigated CENH3 phylogeny and molecular evolution across legumes, focusing on Vicia using phylogenetic reconstruction, sequence alignment, and evolutionary selection analyses.Results Our phylogenetic reconstruction delineated legume species into two major clades (A and B) and revealed a profound contrast between the hypervariable N-terminal tail and the highly conserved histone fold domain (HFD). Within the HFD, the CENP-A targeting domain (CATD) exhibited absolute functional constraint, while the N-terminus demonstrated remarkable evolutionary plasticity. In the genus Vicia, although the exon-intron structure was entirely conserved, substantial sequence polymorphism was identified. Comparative analysis between Vicia sativa and Vicia villosa highlighted species-specific epitope divergence alongside conserved centromere localization. Evolutionary analyses revealed that CENH3 is predominantly under purifying selection, with localized positive selection in specific lineages, whereas canonical H3 exhibited a binary selection pattern dependent on phylogenetic distance.Conclusions Our findings elucidate the evolutionary dynamics of CENH3 in legumes and identify the highly conserved yet functionally distinct CATD as a promising, specific target for developing efficient haploid induction systems through genome editing.

Over the past three decades, molecular cytogenetics has profoundly advanced cotton research, evolving from classical karyotyping to precision breeding design. This review outlines the pivotal role of techniques such as fluorescence in situ hybridization (FISH), genomic in situ hybridization, bacterial artificial chromosome-FISH, and oligo-FISH in enabling accurate chromosome identification, elucidating genome architecture and evolution, and characterizing centromeric organization in Gossypium species. These developments have not only refined our understanding of polyploid cotton genomes but also facilitated the tracing of introgressed chromosomal segments in hybrid breeding programs. By integrating molecular cytogenetics with modern genomic tools, cotton breeding has transitioned toward a precision-oriented approach, allowing for targeted genetic improvements and efficient utilization of wild germplasm. The continued innovation in cytogenetic technologies promises to further enhance the capacity for designing and deploying optimized cotton varieties.

Cardiovascular diseases (CVDs) are the main cause of death and disability worldwide. Existing drug treatments have limitations such as poor targeting, limited efficacy, safety problems, and low patient compliance. Nanozymes, a type of nanomaterial with natural enzyme-like catalytic activity, have shown considerable promise in the treatment of cardiovascular diseases in recent years due to their high stability, designability, and good biocompatibility. This review offers a comprehensive overview of the therapeutic mechanisms and the progress in the application of nanozymes in the treatment of cardiovascular diseases. Nanozymes can efficiently scavenge ROS, regulate oxidative stress and inflammatory response, inhibit apoptosis and abnormal fibrosis, and promote angiogenesis and myocardial repair by mimicking the activities of antioxidant enzymes such as SOD and CAT. Nanozymes can also be utilized as intelligent drug delivery vehicles to achieve targeted thrombolysis, regulate the plaque microenvironment, and integrate diagnosis and treatment. Here, we systematically reviewed and analyzed the related studies in recent years, and introduced the development, classification, and role of nanozymes in a variety of CVDs. In addition, the potential of nanozymes in clinical applications is discussed, hoping to provide new strategies for the precision treatment of CVDs in the future.

Background Meningiomas, among the most common primary intracranial tumors, present significant clinical challenges, particularly due to the propensity for recurrence in higher-grade variants and the paucity of effective non-surgical therapies.Lipid metabolism plays a critical role in tumor progression; however, the specific lipid dysregulation underlying meningioma biology remains incompletely understood. Methods In this study, meningioma tissues and patient-matched arachnoid membrane tissues were collected from 12 patients undergoing meningioma resection surgery. A comprehensive lipidomic analysis was performed on these tissues, and lipid metabolic differences between meningioma and arachnoid tissues were evaluated using multiple t-tests with appropriate correction for multiple comparisons. Results Our analyses revealed pronounced lipidomic remodeling in meningiomas, characterized by an overall increase in total lipid abundance compared with arachnoid tissues. Specifically, phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) were significantly elevated, whereas phosphatidylinositol (PI) levels were reduced. Fatty acid composition also displayed distinct alterations, with decreased saturated fatty acids (SFAs) and increased polyunsaturated fatty acids (PUFAs). In addition, glycerophospholipids and sphingolipids, including sphingomyelin (SM) and ceramide (Cer), exhibited significant remodeling, reflecting profound metabolic reprogramming in meningiomas. Correlation analyses further suggested associations between specific lipid species (e.g., MePC and SM) and clinicopathological features such as tumor size and patient age. Conclusion These findings highlight the pivotal role of lipid metabolic reprogramming in meningioma pathogenesis and underscore the potential of lipidomic profiling to identify biologically relevant biomarkers and therapeutic targets through comparison with arachnoid tissue.