Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification.

Background: Gastroesophageal junction adenocarcinoma (GEJAC) exhibits distinct molecular characteristics due to its unique anatomical location. We sought to investigate effective and reliable molecular classification of GEJAC to guide personalized treatment.

Methods: We analyzed the whole genomic, transcriptomic, T-cell receptor repertoires, and immunohistochemical data in 92 GEJAC patients and delineated the landscape of genetic and immune alterations.

Construction of an Artificially Intelligent Model for Accurate Detection of HCC by Integrating Clinical, Radiological, and Peripheral Immunological Features.

Background: Integrating comprehensive information on hepatocellular carcinoma (HCC) is essential to improve its early detection. We aimed to develop a model with multi-modal features (MMF) using artificial intelligence (AI) approaches to enhance the performance of HCC detection.

Materials And Methods: A total of 1,092 participants were enrolled from 16 centers.

The use of large language models in detecting Chinese ultrasound report errors.

This retrospective study evaluated the efficacy of large language models (LLMs) in improving the accuracy of Chinese ultrasound reports. Data from three hospitals (January-April 2024) including 400 reports with 243 errors across six categories were analyzed. Three GPT versions and Claude 3.

HDAC2 promotes colorectal tumorigenesis by triggering dysregulation of lipid metabolism through YAP1.

Dysfunction of lipid metabolism is important for the development and progression of colorectal cancer, but the underlying mechanisms remain unclear. Here, HDAC2 was identified as highly expressed in both adenoma and colorectal cancer. We aimed to explore the roles and mechanisms of HDAC2 in lipid metabolism in colorectal cancer.

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis.

PerC B-Cells Activation via Thermogenetics-Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells.

During cancer peritoneal metastasis (PM), conventional antigen-presenting cells (dendritic cells, macrophages) promote tumorigenesis and immunosuppression in peritoneal cavity. While intraperitoneal immunotherapy (IPIT) has been used in clinical investigations to relieve PM, the limited knowledge of peritoneal immunocytes has hindered the development of therapeutic IPIT. Here, a dendritic cell-independent, next-generation IPIT is described that activates peritoneal cavity B (PerC B) cell subsets for intraperitoneal anti-tumor immunity via exogenous antigen presentation.

Lactylation: The metabolic accomplice shaping cancer's response to radiotherapy and immunotherapy.

Protein lactylation, an emerging post-translational modification, is providing new insights into tumor biology and challenging our current understanding of cancer mechanisms. Our review illuminates the intricate roles of lactylation in carcinogenesis, tumor progression, and therapeutic responses, positioning it as a critical linchpin connecting metabolic reprogramming, epigenetic modulation, and treatment outcomes. We provide an in-depth analysis of lactylation's molecular mechanisms and its far-reaching impact on cell cycle regulation, immune evasion strategies, and therapeutic resistance within the complex tumor microenvironment.

Self-assembled aptamer nanoparticles for enhanced recognition and anticancer therapy through a lysosome-independent pathway.

Aptamers and aptamer-drug conjugates (ApDCs) have shown some success as targeted therapies in cancer theranostics. However, their stability in complex media and their capacity to evade lysosomal breakdown still need improvement. To address these challenges, we herein developed a one-step self-assembly strategy to improve the stability of aptamers or ApDCs, while simultaneously enhancing their delivery performance and therapeutic efficiency through a lysosome-independent pathway.

OXCT1 succinylation and activation by SUCLA2 promotes ketolysis and liver tumor growth.

Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells.

Epigenetic Mechanisms in the Transcriptional Regulation of Circadian Rhythm in Mammals.

Almost all organisms, from the simplest bacteria to advanced mammals, havea near 24 h circadian rhythm. Circadian rhythms are highly conserved across different life forms and are regulated by circadian genes as well as by related transcription factors. Transcription factors are fundamental to circadian rhythms, influencing gene expression, behavior in plants and animals, and human diseases.

Discovery of -(1,2,4-Thiadiazol-5-yl)benzo[]oxepine-4-carboxamide Derivatives as Novel Antiresistance Androgen Receptor Antagonists.

The ligand-binding pocket of the androgen receptor (AR) is the targeting site of all clinically used AR antagonists. However, various drug-resistant mutations emerged in the pocket. We previously reported a new targeting site at the dimer interface of AR (dimer interface pocket) and identified a novel antagonist M17-B15 that failed in oral administration.

The potential benefits of radiotherapy in elderly patients with early-stage triple-negative breast cancer.

Background: Breast cancer (BC) is the most common cancer in women in the U.S. and a leading cause of cancer-related deaths.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Microenvironment-confined kinetic elucidation and implementation of a DNA nano-phage with a shielded internal computing layer.

Multiple receptor analysis-based DNA molecular computation has been developed to mitigate the off-target effect caused by nonspecific expression of cell membrane receptors. However, it is quite difficult to involve nanobodies into molecular computation with programmed recognition order because of the "always-on" response mode and the inconvenient molecular programming. Here we propose a spatial segregation-based molecular computing strategy with a shielded internal computing layer termed DNA nano-phage (DNP) to program nanobody into DNA molecular computation and build a series of kinetic models to elucidate the mechanism of microenvironment-confinement.

MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1.

Anti-PD-1 therapy, effective in patients with various advanced tumors, still encounters the challenge of insensitivity in most patients. Here, we demonstrate that PD-L1 on tumor cell-derived extracellular vesicles (TEVs) is critical for anti-PD-1 therapy resistance. Reducing endogenous and transferring exogenous TEVs abrogates and induces anti-PD-1 therapy resistance, respectively.

Informatics strategies for early detection and risk mitigation in pancreatic cancer patients.

This review provides a comprehensive overview of the current landscape in pancreatic cancer (PC) screening, diagnosis, and early detection. This emphasizes the need for targeted screening in high-risk groups, particularly those with familial predispositions and genetic mutations, such as BRCA1, BRCA2, and PALB2. This review highlights the sporadic nature of most PC cases and significant risk factors, including smoking, alcohol consumption, obesity, and diabetes.

Bispecific Aptamer-Drug Conjugates Selectively Eliminate Malignant Hematologic Cells for Treating Acute Myeloid Leukemia.

Surface antigen-directed immunotherapy is a curative treatment modality for acute myeloid leukemia (AML) that is characterized by the abundance and stability expression of surface antigens. However, current surface antigen-directed immunotherapies have shown poor outcomes and undesirable mortality rates in treating AML patients, primarily due to acquired resistance that arises from using single-target therapies to address the heterogeneous expression of surface antigens. Hence, in order to improve the efficacy of antigen-specific therapies for treating AML, we designed a bispecific aptamer-drug conjugate.

Extreme Tolerance of Nanoparticle-Protein Corona to Ultra-High Abundance Proteins Enhances the Depth of Serum Proteomics.

The serum nanoparticle-protein corona (NPC) provides specific disease information, thus opening a new avenue for high-throughput in-depth proteomics to facilitate biomarker discovery. Yet, little is known about the interactions between NPs and proteins, and its role in enhanced depth of serum proteomics. Herein, a series of protein spike-in experiments are conducted to systematically investigate protein depletion and enrichment during NPC formation.

Association between osteoarthritis and cognitive function: results from the NHANES 2011-2014 and Mendelian randomization study.

Background: Previous meta-analyses have demonstrated osteoarthritis (OA) is associated with an increased risk of dementia, but these studies were prone to bias based on residual confounding factors and reverse causality.

Objectives: We aimed to investigate associations between OA and cognitive function using data from the National Health and Nutrition Examination Survey (NHANES) and to investigate the causality using Mendelian randomization (MR).

Design: This is a cross-sectional study and MR study.

Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.

Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified. In this study, a single regulatory mechanism of small molecule kinase inhibitors, with crizotinib as the representative drug is elucidated. First, it is discovered that crizotinib induced aberrant lipid metabolism and apoptosis in the liver.

Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving iodine therapy.

This study aimed to establish and validate prognostic nomogram models for patients who underwent I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS).

Efficacy, safety, and quality of life of dabrafenib plus trametinib treatment in Chinese patients with mutation-positive metastatic non-small cell lung cancer.

Background: Dabrafenib plus trametinib (Dab + Tram) is an approved targeted therapy in patients with mutated metastatic non-small cell lung cancer (NSCLC). Here, we report the efficacy, safety, and quality of life (QoL) results of Dab + Tram treatment in Chinese patients with mutation-positive metastatic NSCLC.

Methods: This is a single-arm, open-label, multicentre, phase II study (NCT04452877).

Efficacy and safety of consolidative thoracic radiotherapy after first-line chemoimmunotherapy in patients with extensive-stage small-cell lung cancer: a retrospective cohort study.

Background: Thoracic radiotherapy (TRT) has shown potential benefits in improving local control and overall survival (OS) in chemotherapy-responsive small-cell lung cancer (SCLC) cases. However, its role in the era of chemoimmunotherapy remains underexplored. In the current era of immunotherapy, this study evaluated the efficacy and safety of consolidative TRT (cTRT) in patients with extensive-stage SCLC (ES-SCLC) and assessed its impact on OS.