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Why Sample What You Can Enumerate? Exact Policy Optimization for Genomic Tool Selection

arXiv:2609.10221v1 Announce Type: new Abstract: Reinforcement learning over a frozen reasoner has become a common recipe for teaching a policy which external tools to invoke. We show that this recipe becomes structurally mismatched in specialist scientific settings where the complete tool-subset space is enumerable. There, a small set of recurring computational capabilities covers the domain, so the space of tool subsets is combinatorial yet small enough to enumerate, and GRPO still estimates an action expectation from a handful of sampled rollouts. Worse, the approximation degrades as training succeeds: as the policy concentrates on preferred subsets it resamples them, sampled rewards collide, and the group-normalized advantage vanishes. On genomic reasoning the fraction of questions yielding no reward signal rises from 0.2% under a uniform reference policy to 20.8% after GRPO training. As a remedy, we introduce FGPO (Full-Group Policy Optimization), which (1) scores every tool subset and optimizes the exact action expectation, so each update sees the complete action space, and (2) precomputes the reward of each question--subset pair into an exhaustive table, removing frozen-reasoner calls from the training loop entirely. Across five frozen reasoners and three genomic benchmarks, FGPO outperforms GRPO in all 15 settings by 6.75 points on average and up to 14.20, while a standard on-demand GRPO schedule would require 2.4 times as many frozen-reasoner reward evaluations and, on GenomeQA, FGPO cuts invoked tools per question from 2.36 to 1.40.

Terminalia chebula Retz. aqueous extract exerts anti-adhesive and anti-inflammatory effects against Helicobacter pylori: Insights from lysine metabolism remodeling and fecal metabolomics

J Ethnopharmacol. 2026 Aug 29;373:122318. doi: 10.1016/j.jep.2026.122318. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) infection is a leading risk factor for chronic gastritis, peptic ulcers, and gastric cancer. The escalating antibiotic resistance of H. pylori and adverse effects arising from standard antibiotic regimens have underscored an urgent need for natural, food-complementary therapeutic alternatives. Terminalia chebula Retz., commonly named "Hezi" in traditional Chinese medicine and "Haritaki" in Ayurveda, is a well-recognized edible fruit with a long history of use in alleviating gastrointestinal disorders.

AIM OF THE STUDY: While it has been traditionally recognized for its anti-inflammatory and antimicrobial properties, its anti-adhesive efficacy against H. pylori and the metabolic mechanisms underlying its in vivo effects remain largely unexplored.

MATERIALS AND METHODS: This study adopted multiple analytical and experimental approaches: ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-seq, cell viability and adhesion assays, western blotting, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), metabolomics, and proteomics.

RESULTS: In this study, 15 primary compounds in T. chebula aqueous extract were identified, predominantly tannins. Multi-omics analyses (transcriptomics, metabolomics, and proteomics) revealed that T. chebula aqueous extract significantly inhibited H. pylori adhesion and enriched the lysine degradation pathway. Notably, N-alpha-acetyl-L-lysine was characterized as a key metabolite in fecal metabolomic profiling, which was associated with glycosphingolipid biosynthesis, ferroptosis, HIF-1 signaling, lysosomal function, and arginine metabolism. In vitro assays confirmed that N-alpha-acetyl-L-lysine reduced H. pylori adhesion to GES-1 cells, reversed H. pylori-induced cellular damage, and suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α). In vivo, T. chebula aqueous extract administration markedly alleviated H. pylori-induced gastric inflammation by downregulating IL-6, IL-1β, TNF-α, TGF-β, and IFN-γ. Collectively, these findings demonstrate that T. chebula aqueous extract exerts anti-H. pylori effects by regulating lysine metabolism, with N-alpha-acetyl-L-lysine serving as a key metabolite via fecal metabolomics.

CONCLUSION: These findings highlight T. chebula's promising potential as a functional food ingredient or adjunctive therapy for H. pylori-related diseases, providing a natural, mechanism-based option for clinical intervention.

PMID:42665167 | DOI:10.1016/j.jep.2026.122318

XPO1 inhibitor KPT-330 disrupts the core transcriptional regulatory circuitry of dedifferentiated liposarcoma by modulating the translation process

Oncogene, Published online: 16 April 2026; doi:10.1038/s41388-026-03794-w

XPO1 inhibitor KPT-330 disrupts the core transcriptional regulatory circuitry of dedifferentiated liposarcoma by modulating the translation process
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