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Received — 15 September 2026 ⏭

(Multiomics OR Omics) AND (Pancreatic)
Therapeutic Co-targeting of Oxidative Phosphorylation and Pyrimidine Synthesis Restores Gemcitabine Response in Pancreatic Ductal Adenocarcinoma Wenhui Ouyang · Jie Wang · Jie Chen · Zemin Fang · Ting Wei · Jiazi Qian · Shanying Gui
Transl Res. 2026 Sep 13:S1931-5244(26)00195-7. doi: 10.1016/j.trsl.2026.09.009. Online ahead of print.ABSTRACTGemcitabine resistance remains a major barrier to effective therapy in pancreatic ductal adenocarcinoma (PDAC), and current combination regimens show potential to overcome this resistance. Here, we identify the mitochondrial ribosomal proteins MRPS22 and MRPL3 as key metabolic gatekeepers that maintain mitochondrial OXPHOS and pyrimidine metabolism, thereby promoting pancreatic cancer ce
13 September 2026 at 18:00

Therapeutic Co-targeting of Oxidative Phosphorylation and Pyrimidine Synthesis Restores Gemcitabine Response in Pancreatic Ductal Adenocarcinoma

(Multiomics OR Omics) AND (Pancreatic)

By: Wenhui Ouyang · Jie Wang · Jie Chen · Zemin Fang · Ting Wei · Jiazi Qian · Shanying Gui

13 September 2026 at 18:00

Transl Res. 2026 Sep 13:S1931-5244(26)00195-7. doi: 10.1016/j.trsl.2026.09.009. Online ahead of print.

ABSTRACT

Gemcitabine resistance remains a major barrier to effective therapy in pancreatic ductal adenocarcinoma (PDAC), and current combination regimens show potential to overcome this resistance. Here, we identify the mitochondrial ribosomal proteins MRPS22 and MRPL3 as key metabolic gatekeepers that maintain mitochondrial OXPHOS and pyrimidine metabolism, thereby promoting pancreatic cancer cell proliferation and chemoresistance. Across independent cohorts, high MRPS22/MRPL3 expression associates with poorer survival. Depletion of either gene in PDAC curtailed cell proliferation and xenograft growth, which might be due to an impaired mitochondria function, including destabilized respiratory super-complex assembly, diminished ATP production, and increased oxidative stress. Multi-omics profiling revealed a broad reduction of central-carbon intermediates and a pronounced blockade of de novo pyrimidine synthesis at the dihydroorotate dehydrogenase (DHODH) node. MRPS22 depletion hampered nucleotide-pool generation, and exogenous deoxynucleotides partially rescued PDAC cell growth when MRPs were knocked down. Pharmacologic OXPHOS inhibition increased gemcitabine sensitivity, whereas gemcitabine-resistant derivatives exhibited heightened OXPHOS activity and upregulated mitochondrial ribosomal programs. Co-targeting OXPHOS (antimycin A) or DHODH (brequinar) with gemcitabine produced Loewe synergy in vitro and suppressed growth of gemcitabine-resistant xenografts without affecting body weight. Collectively, these findings established MRPS22/MRPL3 as translation-level drivers of PDAC metabolic fitness and nominate OXPHOS/DHODH blockade as a rational combination strategy to overcome gemcitabine resistance.

PMID:42732873 | DOI:10.1016/j.trsl.2026.09.009

Received — 2 April 2026 ⏭

cs.AI, q-bio.NC updates on arXiv.org
ATP-Bench: Towards Agentic Tool Planning for MLLM Interleaved Generation Yinuo Liu · Zi Qian · Heng Zhou · Jiahao Zhang · Yajie Zhang · Zhihang Li · Mengyu Zhou · Erchao Zhao · Xiaoxi Jiang · Guanjun Jiang
arXiv:2603.29902v1 Announce Type: new Abstract: Interleaved text-and-image generation represents a significant frontier for Multimodal Large Language Models (MLLMs), offering a more intuitive way to convey complex information. Current paradigms rely on either image generation or retrieval augmentation, yet they typically treat the two as mutually exclusive paths, failing to unify factuality with creativity. We argue that the next milestone in this field is Agentic Tool Planning, where the model
1 April 2026 at 12:00

ATP-Bench: Towards Agentic Tool Planning for MLLM Interleaved Generation

cs.AI, q-bio.NC updates on arXiv.org

By: Yinuo Liu · Zi Qian · Heng Zhou · Jiahao Zhang · Yajie Zhang · Zhihang Li · Mengyu Zhou · Erchao Zhao · Xiaoxi Jiang · Guanjun Jiang

1 April 2026 at 12:00

arXiv:2603.29902v1 Announce Type: new Abstract: Interleaved text-and-image generation represents a significant frontier for Multimodal Large Language Models (MLLMs), offering a more intuitive way to convey complex information. Current paradigms rely on either image generation or retrieval augmentation, yet they typically treat the two as mutually exclusive paths, failing to unify factuality with creativity. We argue that the next milestone in this field is Agentic Tool Planning, where the model serves as a central controller that autonomously determines when, where, and which tools to invoke to produce interleaved responses for visual-critical queries. To systematically evaluate this paradigm, we introduce ATP-Bench, a novel benchmark comprising 7,702 QA pairs (including 1,592 VQA pairs) across eight categories and 25 visual-critical intents, featuring human-verified queries and ground truths. Furthermore, to evaluate agentic planning independent of end-to-end execution and changing tool backends, we propose a Multi-Agent MLLM-as-a-Judge (MAM) system. MAM evaluates tool-call precision, identifies missed opportunities for tool use, and assesses overall response quality without requiring ground-truth references. Our extensive experiments on 10 state-of-the-art MLLMs reveal that models struggle with coherent interleaved planning and exhibit significant variations in tool-use behavior, highlighting substantial room for improvement and providing actionable guidance for advancing interleaved generation. Dataset and code are available at https://github.com/Qwen-Applications/ATP-Bench.