An EGFR Co-Amplified and De Novo Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-Driven Gene Programs.

EGFR amplification frequently happens within extrachromosome DNAs (ecDNAs) and is a major mutation in glioblastoma (GBM). However, targeting EGFR for GBM treatments has been unsuccessful. Here we characterized a long non-coding RNA (lncRNA) that is co-amplified with EGFR within ecDNAs that we name hidden EGFR long non-coding downstream RNA (HELDR).

14-3-3 proteins GRF6 and GRF8 negatively regulate phosphate acquisition by interacting with and inhibiting PHR1 in Arabidopsis.

Phosphate starvation response1 (PHR1) is a central transcription factor necessary for low phosphate (LP) response in plants, thus its activity is tightly regulated in plants. Here, we report that two members of the 14-3-3 protein family, GRF6 and GRF8, regulate PHR1 activity and LP response independently of SPX1 in Arabidopsis thaliana. GRF6 and GRF8 physically interact with PHR1, while disruption of both genes causes increased expression of PHR1-targeted phosphate transporter genes and elevated phosphate acquisition.

Therapeutic targeting of circTNK2 with nanoparticles restores tamoxifen sensitivity and enhances NK cell-mediated immunity in ER-positive breast cancer.

Endocrine resistance is a leading cause of relapse in patients with estrogen receptor (ER)-positive breast cancer (ER BC), with tamoxifen resistance being the most prevalent form. circTNK2, a circular RNA, is overexpressed in tamoxifen-resistant BC tissues and is correlated with poor prognosis. circTNK2 encodes a novel 487-amino acid protein, termed C-TNK2-487aa, which inhibits the recruitment of natural killer (NK) cells into BC tumors.

A Single-Cell Atlas of RNA Alternative Splicing in the Glioma-Immune Ecosystem.

Single-cell analysis has refined our understanding of cellular heterogeneity in glioma, yet RNA alternative splicing (AS)-a critical layer of transcriptome regulation-remains underexplored at single-cell resolution. Here, we present a pan-glioma single-cell AS analysis in both tumor and immune cells through integrating seven SMART-seq2 datasets of human gliomas. Our analysis reveals lineage-specific AS across glioma cellular states, with the most divergent AS landscapes between mesenchymal- and neuronal-like glioma cells, exemplified by AS in and .

Targeting PDGFRA-SHP2 Signaling Enhances Radiotherapy in IDH1-Mutant Glioma.

Background: Isocitrate dehydrogenase mutant (IDH-mut) gliomas represent a distinct subtype of glioma, characterized by a relatively better prognosis compared to IDH wildtype (wt) glioblastoma (GBM). Despite this advantage, these tumors remain incurable due to the limited availability of effective treatments. Targeting SHP2, a non-receptor protein tyrosine phosphatase, is a promising therapeutic strategy for several types of human cancers.

Investigating the impact of sickle cell disease on red blood cell transport in complex capillary networks.

Sickle cell disease encompasses a variety of inherited red blood cell (RBC) disorders characterized by abnormal thrombosis, microvascular occlusion, end-organ ischemia, and early mortality. Understanding how sickle RBCs drive abnormal blood flow and stress on the endothelial wall is essential to predict and prevent blockages in blood circulation. While there are studies comparing blood flow velocity and pressure via computational fluid dynamics simulations, there are still open questions about how sickle cells interact with plasma in a complex capillary network.

Oxidative stress induced protein aggregation via GGCT produced pyroglutamic acid in drug resistant glioblastoma.

Drug resistance is a major barrier to cancer therapies and remains poorly understood. Recently, non-mutational mechanisms of drug resistance have been proposed where a more plastic metabolic response can play a major role. Here, we show that upon drug resistance, glioblastoma (GBM) cells have increased oxidative stress, mitochondria function, and protein aggregation.

SORTING NEXIN1 facilitates SALT OVERLY SENSITIVE1 protein accumulation to enhance salt tolerance in Arabidopsis.

The plasma membrane (PM)-localized Na+/H+ antiporter Salt Overly Sensitive1 (SOS1) is essential for plant salt tolerance through facilitating Na+ efflux; however, how SOS1 localization and protein accumulation is regulated in plants remains elusive. Here, we report that Sorting Nexin 1 (SNX1) is required for plant salt-stress tolerance through affecting endosomal trafficking of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of SNX1 caused salt hypersensitivity with increased Na+ accumulation and decreased Na+ efflux in Arabidopsis when challenged with high salinity stress.

Genetic Evidence of in Leaf Morphology Variation of 'Mojo'.

Leaves play a crucial role as ornamental organs in , exhibiting distinct differences across various varieties. Leaf development is intricately linked to processes of cell proliferation and expansion, with cell morphology often regulated by plant cell walls, primarily composed of cellulose. Alterations in cellulose content can impact cell morphology, subsequently influencing the overall shape of plant organs.

RNA splicing analysis deciphers developmental hierarchies and reveals therapeutic targets in adult glioma.

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single-cell RNA-Seq, we uncover a prognostic AS signature linked with neural developmental hierarchies.

CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4.

Background: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis.

Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.

Background: Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo.

Methods: We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC.

Spatially resolved proteomics via tissue expansion.

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity of biological samples, however, it remains technically challenging due to the complexity of the tissue microsampling techniques and mass spectrometry analysis of nanoscale specimen volumes. Here, we describe a spatially resolved proteomics method based on the combination of tissue expansion with mass spectrometry-based proteomics, which we call Expansion Proteomics (ProteomEx). ProteomEx enables quantitative profiling of the spatial variability of the proteome in mammalian tissues at ~160 µm lateral resolution, equivalent to the tissue volume of 0.

Time-averaged cumulative blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction: analysis from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.

Objective: To determine whether time-averaged cumulative blood pressure (cumBP) is associated with the risk of cardiovascular outcomes among patients with heart failure with preserved ejection fraction.

Method: Three thousand, three hundred and thirty participants from Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included in this analysis with a median follow-up of 3 years. CumBP, expressed as mmHg-years, was the sum of mean BP for each pair of successive examinations multiplied by the time.

Protein-protein interaction networks as miners of biological discovery.

Protein-protein interactions (PPIs) form the basis of a myriad of biological pathways and mechanism, such as the formation of protein complexes or the components of signaling cascades. Here, we reviewed experimental methods for identifying PPI pairs, including yeast two-hybrid (Y2H), mass spectrometry (MS), co-localization, and co-immunoprecipitation. Furthermore, a range of computational methods leveraging biochemical properties, evolution history, protein structures and more have enabled identification of additional PPIs.

The double homeobox a pseudogene 8 accelerates cell proliferation, migration, and invasion in colon cancer.

Double homeobox A pseudogene 8 (DUXAP8) is a known tumor promoter in several malignancies. Nonetheless, its function in colon cancer (CC) is indefinite. Herein, we explored the significance of DUXAP8 and its underlying mechanism in CC.

Stratification of follicular thyroid tumours using data-independent acquisition proteomics and a comprehensive thyroid tissue spectral library.

Thyroid nodules occur in about 60% of the population. A major challenge in thyroid nodule diagnosis is to distinguish between follicular adenoma (FA) and carcinoma (FTC). Here, we present a comprehensive thyroid spectral library covering five types of thyroid tissues.

Validation and comparison of three newly-released Thyroid Imaging Reporting and Data Systems for cancer risk determination.

Purpose: To validate and compare diagnostic value of three newly-released Thyroid Imaging Reporting and Data Systems (TIRADS) for cancer risk determination.

Methods: Total 2031 patients with 2465 thyroid nodules were recruited for this study. Ultrasound (US) images were categorized based on three TIRADS editions established by Korean Society of Thyroid Radiology (KSThR), European Thyroid Association (ETA) and American College of Radiology (ACR).