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Cell death and proliferation are at a glance dichotomic events, but occasionally coupled. Caspases, traditionally known to execute apoptosis, play non-apoptotic roles, but their exact mechanism remains elusive. Here, using intestinal stem cells (ISCs), we discovered that activation of caspases induces massive cell proliferation rather than cell death. We elucidate that a positive feedback circuit exists between caspases and JNK, which can simultaneously drive cell proliferation and cell death. In ISCs, signalling from JNK to caspases is defective, which skews the balance towards proliferation. Mechanistically, two-tiered regulation of the DIAP1 inhibitor , through its transcription and its protein localization, exists. This work provides a conceptual framework that explains how caspases perform apoptotic and non-apoptotic functions in vivo and how ISCs accomplish their resistance to cell death.
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http://dx.doi.org/10.26508/lsa.202302238 | DOI Listing |
ACS Appl Bio Mater
September 2025
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
The generation of reactive oxygen species (ROS) through nanozyme-mediated sonocatalytic therapy has demonstrated remarkable therapeutic efficacy in the field of cancer. Nevertheless, it remains a significant challenge for nanozymes with a single catalytic active center to generate sufficient ROS via Fenton or Fenton-like reactions to effectively induce tumor cell death. In order to enhance the catalytic efficacy, we devised and synthesized a multiple active centre and mitochondrial-targeted perovskite nanozyme (NCFP), doped with cobalt (Co) element, and incorporated 4-carboxybutyltriphenylphosphonium bromide (TPP) as a mitochondrial targeting marker for ultrasound (US)-assisted enzyme-like catalytic treatment of tumors.
View Article and Find Full Text PDFSci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
View Article and Find Full Text PDFSci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
View Article and Find Full Text PDFPLoS One
September 2025
Institute of Crop Sciences, Chinese Academy of Agricultural Sciences/National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRl). Ministry of Agriculture and Rural Affairs/Key Laboratory of Crop Gene Resource and Germplasm Enhancement, Ministry of Agriculture and Rural Affairs, Bei
Shade stress alters soybean growth through transcriptomic changes and adaptive responses that optimize light capture and utilization, regulated by a phytohormonal network. This study examined the physiological, morphological, and molecular responses of Guru (shade-tolerant) and Heinong 53 (shade-sensitive) soybean cultivars under 0% (control), 30%, and 70% shade. Results revealed morphological responses where Heinong 53 exhibited greater plant height (52.
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