Macranthoside B Suppresses the Growth of Adenocarcinoma of Esophagogastric Junction by Regulating Iron Homeostasis and Ferroptosis through NRF2 Inhibition.

Background: Macranthoside B (MB) is a saponin compound extracted from hon-eysuckle that has been reported to exhibit significant medicinal values, particularly anti-tumor activities. This study aimed to evaluate the anticancer efficacy of MB in treating adenocarci-noma of the esophagogastric junction (AEG) and elucidate its underlying mechanisms.

Methods: Three AEG cell lines and normal gastric epithelial cells were used to assess the an-ticancer activity of MB in vitro.

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.

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.

Therapeutic Black Phosphorus Nanosheets Elicit Neutrophil Response for Enhanced Tumor Suppression.

Black phosphorus (BP) has demonstrated potential as a drug carrier and photothermal agent in cancer therapy; however, its intrinsic functions in cancer treatment remain underexplored. This study investigates the immunomodulatory effects of polyethylene glycol-functionalized BP (BP-PEG) nanosheets in breast cancer models. Using immunocompetent mouse models-including 4T1 orthotopic BALB/c mice and MMTV-PyMT transgenic mice, it is found that BP-PEG significantly inhibits tumor growth and metastasis without directly inducing cytotoxicity in tumor cells.

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.

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.

TWIST1 Regulates FOXM1/β-Catenin to Promote the Growth, Migration, and Invasion of Ovarian Cancer Cells by Activating MFAP2.

TWIST1 is aberrantly expressed in ovarian cancer (OC). MFAP2 is a downstream target of TWIST1, and we previously found MFAP2 facilitated OC development by activating FOXM1/β-catenin. We planned to investigate the mechanisms of TWIST1 in OC.

Dynamic Genomic Imaging and Tracking in Living Cells by a DNA Origami-Based CRISPR‒dCas9 System.

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated system has displayed promise in visualizing the dynamics of target loci in living cells, which is important for studying genome regulation. However, developing a cell-friendly and rapid transfection method for achieving dynamic and long-term genomic imaging in living cells with high specificity and accuracy is still challenging. Herein, a robust and versatile method is presented that employs a barrel-shaped DNA nanostructure (TUBE) modified with aptamers for loading, protecting, and delivering CRISPR-Cas9 to visualize specific genomic loci in living cells.

Whole lung radiomic features are associated with overall survival in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy.

Background: Several studies have suggested that lung tissue heterogeneity is associated with overall survival (OS) in lung cancer. However, the quantitative relationship between the two remains unknown. The purpose of this study is to investigate the prognostic value of whole lung-based and tumor-based radiomics for OS in LA-NSCLC treated with definitive radiotherapy.

Ubiquitination-related Gene UBTD1 Mediates Poor Prognosis of Colorectal Cancer and Affects Colorectal Cancer Cell Proliferation and Ferroptosis.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, and its occurrence and progression are often regulated by genetic and hereditary factors. Ubiquitination and the associated ubiquitin-binding enzymes and ligases regulate the tumor microenvironment and antitumor immunity to mediate tumor pathogenesis and progression. In this study, we examined the molecular characteristics and immunomodulatory effects of ubiquitination-associated genes that mediate CRC prognosis.

Targeting FOXM1 condensates reduces breast tumour growth and metastasis.

Identifying phase-separated structures remains challenging, and effective intervention methods are currently lacking. Here we screened for phase-separated proteins in breast tumour cells and identified forkhead (FKH) box protein M1 (FOXM1) as the most prominent candidate. Oncogenic FOXM1 underwent liquid-liquid phase separation (LLPS) with FKH consensus DNA element, and compartmentalized the transcription apparatus in the nucleus, thereby sustaining chromatin accessibility and super-enhancer landscapes crucial for tumour metastatic outgrowth.

Validation of the 9th edition of the TNM staging system for limited-stage small cell lung cancer after Resection: A multicenter study.

Objectives: The 9th edition of the tumor-node-metastasis (TNM) staging system for lung cancer was proposed at the 2023 World Conference on Lung Cancer in Singapore. This study aimed to externally validate and compare the latest staging of small-cell lung cancer (SCLC).

Methods: Four hundred and eight patients with limited-stage SCLC were collected after lung resection from four centers.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.

Development and Validation of a Predictive Model for Liver Failure After Transarterial Chemoembolization Using Gadoxetic Acid-Enhanced MRI and Functional Liver Imaging Score.

Rationale And Objectives: Post-transarterial chemoembolization liver failure (PTLF) is a potentially fatal complication of transarterial chemoembolization (TACE). Accurate preoperative prediction of PTLF is crucial for improving patient outcomes. This study aimed to develop and validate a prediction model based on the functional liver imaging score (FLIS) to assess the risk of PTLF.

ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201.

Background: Small cell lung cancer (SCLC) represents a highly aggressive neuroendocrine tumour with a dismal prognosis. Currently, the identification of a specific tumour antigen that can facilitate immune-based therapies for SCLC remains elusive.

Methods: We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse cancer/testis antigens (CTAs) in SCLC cell lines and human tumour specimens.

Efficient and Rapid Enrichment of Extracellular Vesicles Using DNA Nanotechnology-Enabled Synthetic Nano-Glue.

Swift and efficient enrichment and isolation of extracellular vesicles (EVs) are crucial for enhancing precise disease diagnostics and therapeutic strategies, as well as elucidating the complex biological roles of EVs. Conventional methods of isolating EVs are often marred by lengthy and laborious processes. In this study, we introduce an innovative approach to enrich and isolate EVs by leveraging the capabilities of DNA nanotechnology.

Reducing Measurement Deviation by Metastable DNA Probes for Aptamer Thermodynamic Characterization.

DNA reaction equilibrium-based calculations have great potential in thermodynamic characterization, but their widespread applications are hindered by significant measurement deviation of equilibrium concentration. Here, we report the advantages of metastable DNA hybridization in reducing quantification deviation of equilibrium concentration and propose a universal and standardized strategy for measuring aptamer binding energy, termed metastable DNA reference calorimetry (MDRC). We built different MDRC-based algorithms tailored to different aptamer binding models, enabling the calculation of thermodynamic parameters for aptamers with one or more binding sites.

Annotation-free deep learning algorithm trained on hematoxylin & eosin images predicts epithelial-to-mesenchymal transition phenotype and endocrine response in estrogen receptor-positive breast cancer.

Recent evidence indicates that endocrine resistance in estrogen receptor-positive (ER+) breast cancer is closely correlated with phenotypic characteristics of epithelial-to-mesenchymal transition (EMT). Nonetheless, identifying tumor tissues with a mesenchymal phenotype remains challenging in clinical practice. In this study, we validated the correlation between EMT status and resistance to endocrine therapy in ER+ breast cancer from a transcriptomic perspective.

Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity.

Chromothripsis, a hallmark of cancer, is characterized by extensive and localized DNA rearrangements involving one or a few chromosomes. However, its genome-wide frequency and characteristics in urothelial carcinoma (UC) remain largely unknown. Here, by analyzing single-regional and multi-regional whole-genome sequencing (WGS), we present the chromothripsis blueprint in 488 UC patients.

The clinical diagnostic value of right-to-left shunt in cryptogenic stroke under right heart contrast echocardiography: a retrospective case-control study.

Background: About 30% of ischemic strokes do not have a clear cause, which is called cryptogenic stroke (CS). Increasing evidence suggests a potential link between CS and right-to-left shunt (RLS). RLS may lead to CS via paradoxical embolic mechanism.