CT Multidimensional Radiomics Combined with Inflammatory Immune Score For Preoperative Prediction of Pathological Grade in Esophageal Squamous Cell Carcinoma.

Rationale And Objectives: Inflammation and immune biomarkers can promote angiogenesis and proliferation and metastasis of esophageal squamous cell carcinoma (ESCC). The degree of pathological grade reflects the tumor heterogeneity of ESCC. The purpose is to develop and validate a nomogram based on enhanced CT multidimensional radiomics combined with inflammatory immune score (IIS) for predicting poorly differentiated ESCC.

Comprehensive Transcriptomic Analysis Reveals Cell-Type-Specific Roles of Human Odorant Receptors in Glioblastoma and the Tumor Microenvironment.

Odorant receptors (ORs), which constitute approximately 50% of all human G protein-coupled receptors, are increasingly recognized for their diverse roles beyond odor perception, including functions in various pathological conditions like brain diseases and cancers. However, the roles of ORs in glioblastoma (GBM), the most aggressive primary brain tumor with a median survival of only 15 months, remain largely unexplored. Here, we performed an integrated transcriptomic analysis combining The Cancer Genome Atlas RNA-seq and single-cell RNA sequencing data from GBM patients to uncover cell-type-specific roles of ORs within the tumor and its microenvironment.

Adoptive T cell therapy targeting an inducible and broadly shared product of aberrant mRNA translation.

Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Alcohol-associated hepatitis trends before and following the onset of the COVID-19 pandemic across two distinct cohorts in the United States and Hong Kong.

Background & Aims: Alcohol-associated liver disease (ALD) burden has been rising globally, fueled by increases in high-risk alcohol use following the coronavirus disease 2019 (COVID-19) pandemic. We evaluated trends in annual incidence of alcohol-associated hepatitis (AH) before and following the onset of the COVID-19 pandemic across two geographically distinct populations in the USA and Hong Kong.

Methods: Using US national Veterans Affairs (VA) data and Hong Kong territory-wide data, trends in annual incidence of AH were evaluated from 2000 to 2023.

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.

Barley2035: A decade vision on barley research and breeding.

Barley (Hordeum vulgare ssp. vulgare) is one of the oldest founder crops in early human civilization, and has been widely dispersed around the globe to supply human life through livestock feeding and brewing industries. It has been used in innovative research of cytogenetics, biochemistry, and genetics since the early half of the 20 century, facilitated by its mode of reproduction through self-pollination, its true diploid status which has contributed to the accumulation of a plethora of germplasm and mutant resources.

Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.

Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood.

Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics.

Polysaccharide intercellular adhesin (PIA), an exopolysaccharide composed of poly-N-acetyl glucosamine (PNAG), is an essential component in many pathogenic biofilms. Partial deacetylation of PNAG is required for biofilm formation, but limited structural knowledge hinders therapeutic development. Employing a new monoclonal antibody (TG10) that selectively binds highly deacetylated PNAG and an antibody (F598) in clinical trials that binds highly acetylated PNAG, we demonstrate that PIA within the biofilm contains distinct regions of highly acetylated and deacetylated exopolysaccharide, contrary to the previous model invoking stochastic deacetylation throughout the biofilm.

Simultaneous Development of Antiferromagnetism and Local Symmetry Breaking in a Kagome Magnet (CoFe)Sn.

CoSn and FeSn, two kagome-lattice metals, have recently attracted significant attention as hosts of electronic flat bands and emergent physical properties. However, current understandings of their physical properties are limited to knowledge of the average crystal structure. Here, we report the Fe-doping induced coemergence of the antiferromagentic (AFM) order and local symmetry breaking in (CoFe)Sn.

Ulp1 Regulates Cell Proliferation Through INO1 in .

Background/objectives: Ulp1 is a vital regulator of the cell cycle, with its absence leading to G2/M phase arrest in . This study aims to investigate the role of Ulp1 in cell cycle regulation in and to elucidate its mechanisms of action, particularly through the modulation of the gene .

Methods: We generated Ulp1 knockout strains in using the FLP-FRT system and performed RNA sequencing (RNA-seq) to analyze gene expression changes.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Transcription and DNA replication collisions lead to large tandem duplications and expose targetable therapeutic vulnerabilities in cancer.

Despite the abundance of somatic structural variations (SVs) in cancer, the underlying molecular mechanisms of their formation remain unclear. In the present study, we used 6,193 whole-genome sequenced tumors to study the contributions of transcription and DNA replication collisions to genome instability. After deconvoluting robust SV signatures in three independent pan-cancer cohorts, we detected transcription-dependent, replicated-strand bias, the expected footprint of transcription-replication collision (TRC), in large tandem duplications (TDs).

Development of a streamlined NGS-based TCGA classification scheme for gastric cancer and its implications for personalized therapy.

Background: The Cancer Genome Atlas (TCGA) has identified four distinct molecular subtypes of gastric cancer (GC) with prognostic significance: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI)-high, genomically stable (GS), and chromosomal instability (CIN). Unfortunately, the complex analysis required for TCGA classification limits its practical use in clinical settings. Our study sought to devise a next-generation sequencing (NGS)-based method to classify GC more efficiently, serving as a promising biomarker for prognosis and immunotherapy efficacy.

Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.

Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality and threatens global control of tuberculosis disease. The diarylquinoline bedaquiline has recently emerged as a highly efficacious drug against MDR-TB and kills Mycobacterium tuberculosis by inhibiting mycobacterial ATP synthase. However, the mechanisms underlying bedaquiline's efficacy against MDR-TB remain unknown.

CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity.

Doxorubicin is limited in its therapeutic utility due to its life-threatening cardiovascular side effects. Here, we present an integrated drug discovery pipeline combining human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs), CRISPR interference and activation (CRISPRi/a) bidirectional pooled screens, and a small-molecule screening to identify therapeutic targets mitigating doxorubicin-induced cardiotoxicity (DIC) without compromising its oncological effects. The screens revealed several previously unreported candidate genes contributing to DIC, including carbonic anhydrase 12 (CA12).

Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography.

Purpose To develop a deep learning model for the morphologic measurement of unruptured intracranial aneurysms (UIAs) based on CT angiography (CTA) data and validate its performance using a multicenter dataset. Materials and Methods In this retrospective study, patients with CTA examinations, including those with and without UIAs, in a tertiary referral hospital from February 2018 to February 2021 were included as the training dataset. Patients with UIAs who underwent CTA at multiple centers between April 2021 to December 2022 were included as the multicenter external testing set.

YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity.

RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N-methyladenosine (mA) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and mA recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.

Temporal recording of mammalian development and precancer.

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Background: Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study.

Methods: Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke).