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.