Oncogene, Published online: 07 April 2026; doi:10.1038/s41388-026-03760-6

Hypoxia-induced XBP1s-MYDGF axis suppresses ferroptosis through UBQLN1-mediated stabilization of LCN2 in gastric cancer

arXiv:2604.02091v1 Announce Type: cross Abstract: Rerankers play a pivotal role in refining retrieval results for Retrieval-Augmented Generation. However, current reranking models are typically optimized on static human annotated relevance labels in isolation, decoupled from the downstream generation process. This isolation leads to a fundamental misalignment: documents identified as topically relevant by information retrieval metrics often fail to provide the actual utility required by the LLM for precise answer generation. To bridge this gap, we introduce ReRanking Preference Optimization (RRPO), a reinforcement learning framework that directly aligns reranking with the LLM's generation quality. By formulating reranking as a sequential decision-making process, RRPO optimizes for context utility using LLM feedback, thereby eliminating the need for expensive human annotations. To ensure training stability, we further introduce a reference-anchored deterministic baseline. Extensive experiments on knowledge-intensive benchmarks demonstrate that RRPO significantly outperforms strong baselines, including the powerful list-wise reranker RankZephyr. Further analysis highlights the versatility of our framework: it generalizes seamlessly to diverse readers (e.g., GPT-4o), integrates orthogonally with query expansion modules like Query2Doc, and remains robust even when trained with noisy supervisors.

Xiao et al. identify α-KG as a rosacea-associated metabolite that activates the OXGR1-Gq-MYL9 axis in the vascular smooth muscle cells to boost contractility and suppress pathological vasodilation underlying erythema. Cryo-EM reveals a bipartite-acid pocket of OXGR1 that enables structure-guided development of A-1, a selective agonist that alleviates erythema in rosacea-like models.

SPYTAC is a synthetic peptide-programmed targeted protein degradation platform harnessing LRP1 to drive lysosomal degradation of extracellular amyloid-β in the brain and periphery. In 5×FAD mice, SPYTAC treatment efficiently degrades amyloid-β, preserves neurons, and improves cognition with reduced neuroinflammation and microhemorrhage when compared with antibody therapy.

arXiv:2602.07883v2 Announce Type: replace Abstract: Agentic systems powered by Large Language Models (LLMs) have demonstrated remarkable potential in tackling complex, long-horizon tasks. However, their efficacy is fundamentally constrained by static configurations governing agent behaviors, which are fixed prior to execution and fail to adapt to evolving task dynamics. Existing approaches, relying on manual orchestration or heuristic-based patches, often struggle with poor generalization and fragmented optimization. To transcend these limitations, we propose ToolSelf, a novel paradigm enabling tool-driven runtime self-reconfiguration. By abstracting configuration updates as a callable tool, ToolSelf unifies task execution and self-adjustment into a single action space, achieving a phase transition from external rules to intrinsic parameters. Agents can thereby autonomously update their sub-goals and context based on task progression, and correspondingly adapt their strategy and toolbox, transforming from passive executors into dual managers of both task and self. We further devise Configuration-Aware Two-stage Training (CAT), combining rejection sampling fine-tuning with trajectory-level reinforcement learning to internalize this meta-capability. Extensive experiments across diverse benchmarks demonstrate that ToolSelf rivals specialized workflows while generalizing to novel tasks, achieving a 24.1% average performance gain and illuminating a path toward truly self-adaptive agents.