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Breast tumor‐initiating cells (BTICs) of triple‐negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin‐α dependent manner. Nuclear SOSTDC1 interacts with the N‐terminus of the nucleoprotein, chromatin helicase DNA‐binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to β‐transducin repeat‐containing protein (β‐TrCP) binding motifs of CHD1 is found, thereby blocking the β‐TrCP‐CHD1 interaction and inhibiting β‐TrCP‐mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers impose a substantial global health burden, highlighting the necessity for deeper understanding of their intricate pathogenesis and treatment strategies. This review explores the interplay between intratumoral microbiota, tumor metabolism, and major types of GI cancers (including esophageal, gastric, liver, pancreatic, and colorectal cancers), summarizing recent studies and elucidating their clinical implications and future directions. Recent research revealed altered microbial signatures within GI tumors, impacting tumor progression, immune responses, and treatment outcomes. Dysbiosis-induced alterations in tumor metabolism, including glycolysis, fatty acid metabolism, and amino acid metabolism, play critical roles in cancer progression and therapeutic resistance. The integration of molecular mechanisms and potential biomarkers into this understanding further enhances the prognostic significance of intratumoral microbiota composition and therapeutic opportunities targeting microbiota-mediated tumor metabolism. Despite advancements, challenges remain in understanding the dynamic interactions within the tumor microenvironment (TME). Future research directions, including advanced omics technologies and prospective clinical studies, offer promising avenues for precision oncology and personalized treatment interventions in GI cancer. Overall, integrating microbiota-based approaches and molecular biomarkers into GI cancer management holds promise for improving patient outcomes and survival. [ABSTRACT FROM AUTHOR]

BackgroundSilicon carbide junction barrier Schottky (SiC JBS) diode is a kind of power device based on wide bandgap semiconductor. SiC JBS diode is expected to become an important part of electric propulsion systems in the radiation application field in the future space exploration due to its excellent high-voltage, high-frequency and high-power characteristics. However, there are a large number of protons in the typical orbit of spacecraft, which always threaten the stable operation of spacecraft, including its key components.PurposeThis study aims to explore the resist ability of SiC JBSs to the degradation of medium energy proton irradiation, and clarify the mechanism of radiation effect of SiC JBSs from medium energy proton.MethodsBased the proton equivalent displacement damage dose in low Earth orbit for ten years, the SiC JBSs were firstly irradiated using 10 MeV protons at fluences ranging from 3×109 cm-2 to 3×1010 cm-2 at room temperature and without bias voltage. And the macro electrical characteristics of the SiC JBSs both before and after irradiation, including the forward current-voltage (I-V), reverse I-V and capacitance-voltage (C-V) characteristics, were tested. Then the irradiation-induced defects characteristics were tested by deep level transient spectrum (DLTS). Further, the related degradation mechanism that was associated with this phenomenon was also investigated using based on the test data and mathematical calculation. Finally, irradiation experiments of accelerator protons were carried out for commercial SiC JBSs.ResultsThe results show that the forward electrical characteristic of the SiC JBSs is stable, and the leakage current decreases at low reverse safety voltage. But the rated breakdown voltage is seriously degraded with the increase of irradiation fluence. The main contribution to the change of SiC JBSs characteristics originates from the increase of interface charge, deep level defects and Schottky barrier height, and the decrease of carrier density and carrier diffusion length in the drift region.ConclusionsAnalysis of the radiation damage process and mechanism of SiC JBSs in this study provides a research basis for its evaluation and verification before applied to medium energy proton environment.

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults. METHODS: This population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults. Highlights: We used hierarchical clustering to generate five clusters of multimorbidity.The presence and load of multimorbidity were associated with dementia and mild cognitive impairment.Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers. [ABSTRACT FROM AUTHOR]

With the rapid development of nuclear energy and space technology, application of high-voltage power devices based on SiC, especially the SiC MOSFET, is increasing. The problems of single event effect (SEE) caused by high-energy particle radiation in the radiation environment, such as, single event burnout (SEB) and single event gate rupture (SEGR), are becoming more and more prominent. In order to systematically understand the research progress of SiC MOSFET SEE, and accelerate the research of SiC MOSFET SEE mechanism and its radiation hardening technologies, the advantages of SiC MOSFET and the key problems in its radiation application are first demonstrated. Then, the simulation calculation, irradiation experiment and corresponding research results of SiC MOSFET SEE at home and abroad are comprehensively reviewed, and the main focus of related research is summarized. In addition, the possible reasons for the high sensitivity of SiC MOSFET to SEE is analyzed. Finally, possible future research directions of SiC MOSFET SEE are discussed according to current existing problems in this field. By systematically summarizing the research progress of SiC MOSFET SEE worldwide, it is expected to provide valuable reference for fully revealing the physical mechanism of SiC MOSFET SEE, and even further improving the radiation hardening technologies of SiC MOSFET to prevent the problem from SEE.