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Sensing Intelligence as a Trainable Metamaterial Property
Fetal monitoring for high-risk pregnancies using a wearable ultrasound patch
Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03140-1
A wearable ultrasound device is optimized for continuous monitoring of pregnancies.Deubiquitinase USP35 regulates MDM4 degradation to promote endothelial ferroptosis and renal injury progression
Cell Death Discovery, Published online: 25 May 2026; doi:10.1038/s41420-026-03128-5
Deubiquitinase USP35 regulates MDM4 degradation to promote endothelial ferroptosis and renal injury progressionIC3-Evolve: Proof-/Witness-Gated Offline LLM-Driven Heuristic Evolution for IC3 Hardware Model Checking
Do Emotions in Prompts Matter? Effects of Emotional Framing on Large Language Models
Evaluating large language models for simplifying non-English medical consent with clinician involvement
npj Digital Medicine, Published online: 01 April 2026; doi:10.1038/s41746-026-02591-9
Evaluating large language models for simplifying non-English medical consent with clinician involvementEditing strigolactone hormone receptor for robust antiviral silencing in rice
AgentSLR: Automating Systematic Literature Reviews in Epidemiology with Agentic AI
SRAM-Based Compute-in-Memory Accelerator for Linear-decay Spiking Neural Networks
HKDC1-Mediated Polyamine Rewiring Drives Lenvatinib Resistance and Immune Escape in Hepatocellular Carcinoma
Clin Mol Hepatol. 2026 Mar 11. doi: 10.3350/cmh.2025.1269. Online ahead of print.
ABSTRACT
BACKGROUND/AIMS: Lenvatinib resistance and immune exclusion limit outcomes in HCC. We hypothesized that metabolic rewiring orchestrates resistance to lenvatinib and PD-1 blockade.
METHODS: We established LS/LR HCC models and employed multi-omics (proteomics/RNA-seq), ChIP, luciferase, and RIP assays to map HKDC1 regulation. Tumor immunity was profiled by scRNA-seq, mIHC, and flow cytometry. SPD + lenvatinib efficacy was tested in cell lines, patient-derived organoids/xenografts. Tested therapy effect in an immunocompetent hydrodynamic HCC model with hepatocyte-specific Hkdc1 deletion; and analyzed a postoperative cohort (n = 40) treated with lenvatinib + PD-1.
RESULTS: HKDC1, upregulated in LR HCC, was transcriptionally activated by USF1 and promoted SMS-mediated polyamine rewiring. This impaired CD8⁺ T-cell metabolism, reversible by HKDC1 knockdown or spermidine (SPD). SPD synergized with lenvatinib, triggering autophagy and suppressing tumor growth in vitro and in vivo. High HKDC1 predicted poor response and survival in patients receiving lenvatinib + aPD-1.
CONCLUSIONS: A USF1/HKDC1/SMS axis couples polyamine metabolism to immune dysfunction and lenvatinib resistance. HKDC1 is a predictive biomarker and therapeutic node and support polyamine-axis modulation to sensitize HCC to lenvatinib plus PD-1 therapy.
PMID:41812646 | DOI:10.3350/cmh.2025.1269