Multi-omics profiling reveals PLEKHA6 as a modulator of β-catenin signaling and therapeutic vulnerability in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains the most prevalent and lethal subtype of lung cancer, largely due to late diagnosis and therapeutic resistance. In this study, we conducted a comprehensive multi-omics analysis to characterize the pleckstrin homology domain-containing (PLEKHA) family gene in LUAD. Among the eight members, PLEKHA6 was uniquely overexpressed in LUAD tissues and significantly associated with poor prognosis.

Aberrant expression of nuclear prothymosin α contributes to epithelial-mesenchymal transition in lung cancer.

Elevated expression of prothymosin α (ProT) is frequently observed in cancers, but the underlying molecular mechanism remains poorly understood. Here, we report the clinical relevance of ProT expression and its correlation with lung cancer progression. We have shown that ProT was highly expressed in early-stage lung cancer, exhibiting nuclear localization; on the contrary, a loss of nuclear ProT expression was detected in late-stage tumor specimens.

Emerging Roles of ACTL6A as an Oncogenic Hub: Transcriptional Regulation and Beyond.

The malignant progression of human cancer is dictated by specific regulatory hubs coordinating multiple signaling modules. Identifying key oncogenic hubs of human cancers may lay the groundwork for developing breakthrough therapeutic strategies. Actin-like 6A (ACTL6A; also known as BAF53A) was originally identified as a chromatin remodeling factor involved in the transcriptional regulation of genes, especially in stem and progenitor cells.

OCT4 promotes lung cancer progression through upregulation of VEGF-correlated chemokine-1.

Embryonic development and tumor genesis share numerous similarities, with OCT4 standing out as a pivotal transcription factor in embryonic development. Expression of OCT4 is associated with poor prognosis of lung adenocarcinoma. VEGF-correlated chemokine-1 (VCC-1), also known as C-X-C motif chemokine ligand 17 (CXCL17), has been suggested to play a role in promoting tumor angiogenesis and metastasis.

Mean pulmonary artery pressure prediction with explainable multi-view cardiovascular magnetic resonance cine series deep learning model.

Background: Pulmonary hypertension (PH) is a heterogeneous condition and regardless of etiology impacts negatively on survival. Diagnosis of PH is based on hemodynamic parameters measured invasively at right heart catheterization (RHC); however, a non-invasive alternative would be clinically valuable. Our aim was to estimate RHC parameters non-invasively from cardiac magnetic resonance (MR) data using deep learning models and to identify key contributing imaging features.

Combined HDAC8 and checkpoint kinase inhibition induces tumor-selective synthetic lethality in preclinical models.

The elevated level of replication stress is an intrinsic characteristic of cancer cells. Targeting the mechanisms that maintain genome stability to further increase replication stress and thus induce severe genome instability has become a promising approach for cancer treatment. Here, we identify histone deacetylase 8 (HDAC8) as a drug target whose inactivation synergized with the inhibition of checkpoint kinases to elicit substantial replication stress and compromise genome integrity selectively in cancer cells.

Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: and Studies Including Patient-Derived Organoids.

Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for cytotoxicity against HCT-116 cells (human colorectal cancer cell lines).

HSP90/LSD1 dual inhibitors against prostate cancer as well as patient-derived colorectal organoids.

The rational installation of pharmacophores targeting HSP90 and LSD1 axes has achieved significant anti-cancer capacity in prostate and colorectal cancer. Among the series of hybrids, inhibitor 6 exhibited remarkable anti-proliferative activity against prostate cancer cell lines PC-3 and DU145, with GI values of 0.24 and 0.

ASPM stabilizes the NOTCH intracellular domain 1 and promotes oncogenesis by blocking FBXW7 binding in hepatocellular carcinoma cells.

Notch signaling is aberrantly activated in approximately 30% of hepatocellular carcinoma (HCC), significantly contributing to tumorigenesis and disease progression. Expression of the major Notch receptor, NOTCH1, is upregulated in HCC cells and correlates with advanced disease stages, although the molecular mechanisms underlying its overexpression remain unclear. Here, we report that expression of the intracellular domain of NOTCH1 (NICD1) is upregulated in HCC cells due to antagonism between the E3-ubiquitin ligase F-box/WD repeat-containing protein 7 (FBXW7) and the large scaffold protein abnormal spindle-like microcephaly-associated protein (ASPM) isoform 1 (ASPM-i1).

Deep learning based automated left ventricle segmentation and flow quantification in 4D flow cardiac MRI.

Background: 4D flow MRI enables assessment of cardiac function and intra-cardiac blood flow dynamics from a single acquisition. However, due to the poor contrast between the chambers and surrounding tissue, quantitative analysis relies on the segmentation derived from a registered cine MRI acquisition. This requires an additional acquisition and is prone to imperfect spatial and temporal inter-scan alignment.

Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers.

Despite recent advances in molecularly targeted therapies and immunotherapies, the effective treatment of advanced-stage cancers remains a largely unmet clinical need. Identifying driver mechanisms of cancer aggressiveness can lay the groundwork for the development of breakthrough therapeutic strategies. Assembly factor for spindle microtubules (ASPM) was initially identified as a centrosomal protein that regulates neurogenesis and brain size.

Modelling chloroform in indoor swimming pool air and water: the influences of internal air circulation and occupants.

The release of chloroform from water to air in an indoor swimming pool (ISP) exhibits complex physicochemical interactions among many variables, including environmental conditions, occupant activities, and geometry of the ISP. By combining the relevant variables, a structured mathematical model, the double-layer air compartment (DLAC) model, was developed to predict the level of chloroform in ISP air. A physical parameter, the indoor airflow recycle ratio (R), was incorporated into the DLAC model due to internal airflow circulation resulting in the ISP structural configuration.

Deep learning-based prediction of intra-cardiac blood flow in long-axis cine magnetic resonance imaging.

Purpose: We aimed to design and evaluate a deep learning-based method to automatically predict the time-varying in-plane blood flow velocity within the cardiac cavities in long-axis cine MRI, validated against 4D flow.

Methods: A convolutional neural network (CNN) was implemented, taking cine MRI as the input and the in-plane velocity derived from the 4D flow acquisition as the ground truth. The method was evaluated using velocity vector end-point error (EPE) and angle error.

ASPM Activates Hedgehog and Wnt Signaling to Promote Small Cell Lung Cancer Stemness and Progression.

Unlabelled: Small cell lung cancer (SCLC) is among the most aggressive and lethal human malignancies. Most patients with SCLC who initially respond to chemotherapy develop disease relapse. Therefore, there is a pressing need to identify novel driver mechanisms of SCLC progression to unlock treatment strategies to improve patient prognosis.

Alpha-Mangostin Reduces Pericellular Fibronectin on Suspended Tumor Cells and Therapeutically, but Not Prophylactically, Suppresses Distant Metastasis.

Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) exhibit potent cancer chemopreventive properties, whether they can prophylactically and therapeutically be used as dietary nutraceuticals to prevent distant metastasis by suppressing periFN assembly on STCs within the circulation remains obscure. Immunofluorescence staining, MTT assays, flow cytometric assays, immunoblotting, and experimental metastasis mouse models were used to detect the effects of MP extracts or α-MG on periFN on STCs, tumor cell proliferation and apoptosis, the AKT activity, and tumor lung metastasis.

Revealing Unforeseen Diagnostic Image Features With Deep Learning by Detecting Cardiovascular Diseases From Apical 4-Chamber Ultrasounds.

Background With the increase of highly portable, wireless, and low-cost ultrasound devices and automatic ultrasound acquisition techniques, an automated interpretation method requiring only a limited set of views as input could make preliminary cardiovascular disease diagnoses more accessible. In this study, we developed a deep learning method for automated detection of impaired left ventricular (LV) function and aortic valve (AV) regurgitation from apical 4-chamber ultrasound cineloops and investigated which anatomical structures or temporal frames provided the most relevant information for the deep learning model to enable disease classification. Methods and Results Apical 4-chamber ultrasounds were extracted from 3554 echocardiograms of patients with impaired LV function (n=928), AV regurgitation (n=738), or no significant abnormalities (n=1888).

Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity.

Resistance to antitumor treatment contributes to patient mortality. Functional proteomic screening of organoids derived from chemotherapy-treated patients with breast cancer identified nuclear receptor corepressor 2 (NCOR2) histone deacetylase as an inhibitor of cytotoxic stress response and antitumor immunity. High NCOR2 in the tumors of patients with breast cancer predicted chemotherapy refractoriness, tumor recurrence and poor prognosis.

Toward automated segmentation for acute ischemic stroke using non-contrast computed tomography.

Purpose: Non-contrast computed tomography (NCCT) is a first-line imaging technique for determining treatment options for acute ischemic stroke (AIS). However, its poor contrast and signal-to-noise ratio limit the diagnosis accuracy for radiologists, and automated AIS lesion segmentation using NCCT also remains a challenge. In this paper, we propose R2U-RNet, a novel model for AIS lesion segmentation using NCCT.

Integrating ensemble systems biology feature selection and bimodal deep neural network for breast cancer prognosis prediction.

Breast cancer is a heterogeneous disease. To guide proper treatment decisions for each patient, robust prognostic biomarkers, which allow reliable prognosis prediction, are necessary. Gene feature selection based on microarray data is an approach to discover potential biomarkers systematically.

Depleting RhoA/Stress Fiber-Organized Fibronectin Matrices on Tumor Cells Non-Autonomously Aggravates Fibroblast-Driven Tumor Cell Growth.

Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, how it is regulated in adherent tumor cells and the role of periFN in primary tumor growth remain elusive. Techniques of RNAi, plasmid transfections, immunoblotting, fluorescence/immunohistochemistry staining, cell proliferation assays, and primary tumor growth in C57BL6 mice and Fischer 344 rats were employed in this study.

Fibronectin in Cancer: Friend or Foe.

The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis.

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues.

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis.

Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer.

Cancer is a major cause of death. The outcomes of current therapeutic strategies against cancer often ironically lead to even increased mortality due to the subsequent drug resistance and to metastatic recurrence. Alternative medicines are thus urgently needed.

Pterostilbene prevents AKT-ERK axis-mediated polymerization of surface fibronectin on suspended lung cancer cells independently of apoptosis and suppresses metastasis.

Background: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger pro-apoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored.

Kinetics for the distribution of acrylamide in French fries, fried oil and vapour during frying of potatoes.

Kinetic analysis for the formation of acrylamide in heated foods has been typically performed using only measured data of acrylamide in foods; however, its possible loss caused by release from heated foods into fried oil and air has seldom been considered. The results obtained from the monitoring of acrylamide by frying French fries indicated that acrylamide is distributed in three phases: French fries, frying oil, and air. From the evolved gas analysis of acrylamide and the measured concentration profile of the total acrylamide amount present in these phases, the kinetic behaviour for acrylamide formation does not obey the commonly used model of two-step consecutive reactions during frying, while a lumped kinetic model was proposed for the total acrylamide amount.