Reading view
From Prompt Optimization to Multi-Dimensional Credibility Evaluation: Enhancing Trustworthiness of Chinese LLM-Generated Liver MRI Reports -- with Preliminary Extension to Lung Cancer
Kaempferol functionally reprograms CD47 signaling to promote cytoprotection and attenuate oxeiptosis in severe acute pancreatitis
Phytomedicine. 2026 May 15;157:158305. doi: 10.1016/j.phymed.2026.158305. Online ahead of print.
ABSTRACT
BACKGROUND: Severe acute pancreatitis (SAP) lacks targeted therapies, and massive loss of functional pancreatic acinar cells (PAC) drives mortality. Kaempferol (KA) possesses well-established anti-inflammatory and cytoprotective activities and is derived from herbal medicinal plants, but its direct molecular targets and mechanism of action in SAP remain undefined.
PURPOSE: To evaluate the protective effects of KA against SAP and to elucidate its molecular mechanism of specific action, with a focus on identifying the direct cellular target through which KA exerts its cytoprotective effects.
STUDY DESIGN: Gain‑/loss‑of‑function in vitro and PAC‑specific CD47 SAP mouse models, combined with multi‑omics screening and biophysical assays.
METHODS: CD47 manipulation (siRNA/overexpression) was performed in primary PACs and cell lines, combined with WT/CD47-/-/Mist1‑CD47‑iOE (PAC‑specific) mouse models. Network pharmacology, transcriptomics and proteomics were integrated to screen and validate KA's protective effects. Computational‑experimental approaches (molecular docking/dynamics, CETSA, SPR, co‑IP, pharmacological epistasis) characterized KA's allosteric modulation of CD47 signaling.
RESULTS: CD47 was upregulated in SAP; its knockout reduced PAC death via KEAP1/PGAM5/AIFM1-driven oxeiptosis. KA reduced PAC death across genotypes, afforded no extra benefit in CD47-KO, and was not overridden by CD47‑OE. Mechanistically, KA allosterically binds CD47 ectodomain, stabilizes the CD47‑ UBQLN1 complex, and redirects signaling from Gαi‑mediated death to Gβγ/ ERK/NRF2‑mediated survival. ERK inhibition attenuated KA's protection. KA's action was CD47‑dependent.
CONCLUSION: This study identifies anti-oxeiptosis as a novel pharmacological activity of KA in SAP. This is achieved through allosteric modulation of CD47, redirecting its signaling from death‑promoting to a protective axis via activating Gβγ/ERK/NRF2 to suppress oxeiptosis. These findings reveal the CD47‑oxeiptosis axis as a therapeutic target and position KA as a promising candidate for SAP therapy, adding a new mechanistic dimension to KA's known pharmacological profile.
PMID:42184499 | DOI:10.1016/j.phymed.2026.158305
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applications
Cell Death Discovery, Published online: 23 May 2026; doi:10.1038/s41420-026-03147-2
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applicationsSkillX: Automatically Constructing Skill Knowledge Bases for Agents
ForestPrune: High-ratio Visual Token Compression for Video Multimodal Large Language Models via Spatial-Temporal Forest Modeling
Deciphering lung adenocarcinoma heterogeneity: a multi-omics approach reveals nuclear division fibroblasts as prognosticators and therapeutic targets
J Transl Med. 2026 Mar 20. doi: 10.1186/s12967-026-08022-3. Online ahead of print.
ABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is a predominant contributor to cancer‑related mortality globally. Lung‑associated fibroblasts (LAFs) are intricately linked to tumorigenesis and the tumor microenvironment (TME), but their heterogeneity and prognostic relevance in LUAD remain incompletely understood. This study aimed to systematically characterize LAF subsets across the spectrum of pulmonary disease, identify LAF subpopulations associated with LUAD prognosis, and construct a robust LAF‑based prognostic signature.
METHODS: We employed a multi-omics approach, leveraging bulk RNA data of 2719 patients from 19 LUAD cohorts, single-cell RNA (scRNA) sequencing data of 368,904 cells from 93 samples, and spatial transcriptomics data of 15,673 spots from 6 samples to characterize the landscape of LAFs across various stages of pulmonary disease. We employed multiple advanced machine learning algorithms to construct and validate a robust nuclear division LAFs (nLAFs) risk score (nLRS) prediction model.
RESULTS: We observed a dynamic and gradual increase in the proportion of LAFs during the progression of LUAD. Throughout this process, we identified nine LAFs subtypes and found nLAFs are significantly associated with the prognosis of LUAD. Utilizing 100 machine learning algorithm combinations and integrating nLAFs marker genes, we developed a five gene based nLRS model, which demonstrated superior performance than other 49 published models in predicting clinical outcomes for LUAD. Additionally, we observed distinct biological functions and immune cell infiltration in the TME between high and low nLRS groups. Exploratory analysis of pan-cancer immunotherapy cohorts suggested that patients with high nLRS scores may exhibit resistance to immunotherapy in some cancer types, but prospective validation in LUAD-specific cohorts is required. Conversely, high nLRS patients displayed increased sensitivity to chemotherapeutic and targeted therapies in preclinical models.
CONCLUSION: Our study introduces a candidate five-gene signature derived from nLAFs that may serve as a robust prognostic biomarker pending prospective validation, offering insights into personalized therapeutic strategies for LUAD patients.
PMID:41862916 | DOI:10.1186/s12967-026-08022-3
Breast Cancer Screening Knowledge and Sentiments in Singaporean Women: Mixed Methods Study Using Topic Modeling, Sentiment Analysis, and Structured Questionnaire Data
RetroAgent: From Solving to Evolving via Retrospective Dual Intrinsic Feedback
Learning Quadruped Walking from Seconds of Demonstration
CRTAM inhibition mitigates toxicity of immune checkpoint inhibitors without antitumor efficacy trade-off
Nature Cancer, Published online: 05 March 2026; doi:10.1038/s43018-026-01135-0
Dong and colleagues report that blockade of T cell-expressed cytotoxic and regulatory T cell molecule results in selective mitigation of immune-related toxicities without affecting antitumor efficacy of immune checkpoint inhibitors.