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Determined by User Needs: A Salient Object Detection Rationale Beyond Conventional Visual Stimuli
Agentization of Digital Assets for the Agentic Web: Concepts, Techniques, and Benchmark
Discrete Prototypical Memories for Federated Time Series Foundation Models
Cog-DRIFT: Exploration on Adaptively Reformulated Instances Enables Learning from Hard Reasoning Problems
Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer
Oncogene, Published online: 04 April 2026; doi:10.1038/s41388-026-03764-2
Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancerIsobavachalcone exerts anti-gastric cancer effects by targeting dihydroorotate dehydrogenase to induce ROS release and activating the STING pathway
Phytomedicine. 2026 Mar 27;155:158126. doi: 10.1016/j.phymed.2026.158126. Online ahead of print.
ABSTRACT
BACKGROUND: Mitochondrial damage can induce the release of mitochondrial DNA (mtDNA), leading to oxidative stress and activation of immune responses. Targeting mitochondrial dysfunction may thus represent a therapeutic strategy for gastric cancer. Isobavachalcone (IBC), a prenylated chalcone derived from Psoralea corylifolia L., has demonstrated antitumor activity, but its mechanism of action remains unclear, limiting its clinical application.
PURPOSE: This study aimed to investigate the antitumor effects of IBC in gastric cancer and to elucidate the underlying molecular mechanisms, with a focus on mitochondrial damage and immune activation.
STUDY DESIGN: The study combined in vitro and in vivo assays with multi-omics sequencing and network pharmacology to identify IBC's therapeutic target and downstream signaling pathways.
METHODS: Gastric cancer cells and mouse models were treated with IBC to assess its inhibitory effects. Multi-omics approaches and network pharmacology were used to identify potential targets. ROS production, mitochondrial membrane integrity, and immune pathway activation were evaluated via biochemical and molecular assays.
RESULTS: IBC significantly suppresses gastric cancer growth both in vitro and in vivo. Integrated analysis identifies dihydroorotate dehydrogenase (DHODH) as a direct target of IBC. DHODH deficiency can induce mitochondrial membrane remodeling and STING pathway activation. Inhibition of DHODH by IBC induces ROS accumulation, mitochondrial membrane remodeling, and activation of the STING pathway, promoting antitumor immune responses. This study demonstrates that IBC enhances antitumor immunity in gastric cancer through mitochondrial damage-mediated mechanisms.
CONCLUSION: IBC exerts dual antitumor and immunostimulatory effects in gastric cancer by targeting DHODH, inducing mitochondrial damage, and activating the STING pathway, highlighting its promising therapeutic potential in gastric cancer.
PMID:41931998 | DOI:10.1016/j.phymed.2026.158126
Isobavachalcone exerts anti-gastric cancer effects by targeting dihydroorotate dehydrogenase to induce ROS release and activating the STING pathway
Phytomedicine. 2026 Mar 27;155:158126. doi: 10.1016/j.phymed.2026.158126. Online ahead of print.
ABSTRACT
BACKGROUND: Mitochondrial damage can induce the release of mitochondrial DNA (mtDNA), leading to oxidative stress and activation of immune responses. Targeting mitochondrial dysfunction may thus represent a therapeutic strategy for gastric cancer. Isobavachalcone (IBC), a prenylated chalcone derived from Psoralea corylifolia L., has demonstrated antitumor activity, but its mechanism of action remains unclear, limiting its clinical application.
PURPOSE: This study aimed to investigate the antitumor effects of IBC in gastric cancer and to elucidate the underlying molecular mechanisms, with a focus on mitochondrial damage and immune activation.
STUDY DESIGN: The study combined in vitro and in vivo assays with multi-omics sequencing and network pharmacology to identify IBC's therapeutic target and downstream signaling pathways.
METHODS: Gastric cancer cells and mouse models were treated with IBC to assess its inhibitory effects. Multi-omics approaches and network pharmacology were used to identify potential targets. ROS production, mitochondrial membrane integrity, and immune pathway activation were evaluated via biochemical and molecular assays.
RESULTS: IBC significantly suppresses gastric cancer growth both in vitro and in vivo. Integrated analysis identifies dihydroorotate dehydrogenase (DHODH) as a direct target of IBC. DHODH deficiency can induce mitochondrial membrane remodeling and STING pathway activation. Inhibition of DHODH by IBC induces ROS accumulation, mitochondrial membrane remodeling, and activation of the STING pathway, promoting antitumor immune responses. This study demonstrates that IBC enhances antitumor immunity in gastric cancer through mitochondrial damage-mediated mechanisms.
CONCLUSION: IBC exerts dual antitumor and immunostimulatory effects in gastric cancer by targeting DHODH, inducing mitochondrial damage, and activating the STING pathway, highlighting its promising therapeutic potential in gastric cancer.
PMID:41931998 | DOI:10.1016/j.phymed.2026.158126
The Latent Space: Foundation, Evolution, Mechanism, Ability, and Outlook
DR-LoRA: Dynamic Rank LoRA for Fine-Tuning Mixture-of-Experts Models
Bias Is a Subspace, Not a Coordinate: A Geometric Rethinking of Post-hoc Debiasing in Vision-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 involvementScaling the Long Video Understanding of Multimodal Large Language Models via Visual Memory Mechanism
6GAgentGym: Tool Use, Data Synthesis, and Agentic Learning for Network Management
The 1000 Chinese Pangenome empowers medical and population genetics
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10315-y
Development of the pangenome-informed genome assembly (PIGA) workflow enabled the generation of 1,116 diploid genome assemblies (55 de novo and 1,061 pangenome-informed), representing an extensive resource of medically relevant genic variations.PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments
ForestPrune: High-ratio Visual Token Compression for Video Multimodal Large Language Models via Spatial-Temporal Forest Modeling
ImplicitRM: Unbiased Reward Modeling from Implicit Preference Data for LLM alignment
TRACE: A Multi-Agent System for Autonomous Physical Reasoning in Seismological
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