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FlowCPO: A Unified Divergence View of Preference Alignment for Flow Models

arXiv:2609.09905v1 Announce Type: cross Abstract: Preference alignment for flow and diffusion models now spans online reinforcement learning and offline preference optimization, but the relation between these methods remains unclear. In particular, existing forward-process alignment methods require fresh samples from the current model, while offline methods based on fixed preference pairs rely primarily on positive-only fine-tuning or DPO-style likelihood-ratio surrogates. We organize these approaches through a divergence-based framework and introduce FlowCPO, an offline forward-KL objective that uses both preferred and dispreferred samples without online rollouts. For linear interpolation, we show under explicit regularity conditions that the forward-KL objective is bounded by a contrastive flow matching loss, yielding a tractable surrogate on fixed data. We further show that this loss is nonnegative, whereas the signed regression loss of simplified FlowDPO can be unbounded below. In the in-domain setting, FlowCPO achieves higher mean GenEval and OCR scores than the evaluated baselines, reaching 0.84 and 0.87 versus 0.81 and 0.74 for FlowDPO at CFG 3.0. In the out-of-domain setting, the results are mixed, with the best GenEval result but lower reward scores than RFT on several metrics.

Targeting KRAS reprograms a Treg-dominant immunosuppressive microenvironment and sensitizes KRAS-mutant gastric adenocarcinoma to CTLA-4 immunotherapy

Sci China Life Sci. 2026 Sep 3. doi: 10.1007/s11427-026-3438-4. Online ahead of print.

ABSTRACT

Oncogenic KRAS mutations define a distinct molecular subset of gastric adenocarcinoma (GA), yet their impact on the tumor immune microenvironment remains incompletely understood. In this study, we established a genetically faithful and immunocompetent KRASG12D-driven mouse model of GA, together with matched organoids and cell lines, to investigate how oncogenic KRAS shapes tumor-immune interactions. KRAS-mutant tumors consistently developed an immunosuppressive microenvironment characterized by enrichment of regulatory T cells (Tregs), accompanied by reduced cytotoxic lymphocyte infiltration and intrinsic resistance to PD-1 blockade. Although pharmacologic targeting of KRAS effectively suppressed tumor growth and increased immune cell infiltration, functional immune analyses revealed persistent Treg-mediated immunosuppression that limited effective antitumor immunity. Mechanistically, TGF-β signaling was required to maintain Treg dominance and suppress effector T cell function in KRAS-driven tumors. Importantly, disruption of this suppressive axis through combined KRAS inhibition and CTLA-4 blockade attenuated TGF-β activity, impaired Treg function, and enhanced antitumor immune responses in vivo. Collectively, these findings identify oncogenic KRAS as a key regulator of TGF-β-dependent immune suppression in GA and provide mechanistic insight into immune evasion within this molecular subtype.

PMID:42714795 | DOI:10.1007/s11427-026-3438-4

Foaming photopolymers as a high-resolution biomimetic printing platform

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-10968-9

Deep-foam photolithography uses light-controlled polymer foaming to create high-resolution, multifunctional microstructures with tunable optical, wetting and fluid-handling properties for advanced manufacturing applications.

Genomics and social practices at Mogou and other Gansu sites during prehistoric trans-Eurasian exchange

Ancient DNA from 149 individuals at 11 sites in Gansu, China, dated to around 4,700–3,000 years ago, reveals human population history during early transcontinental exchanges of agriculture and technology, as well as contemporary social practices, at the large Mogou cemetery.

DHCR24<sup>+</sup> tumor epithelial cells drive cisplatin resistance in bladder cancer by enhancing cholesterol metabolism to activate lipid raft-associated MAPK signaling

Oncogene, Published online: 29 August 2026; doi:10.1038/s41388-026-03967-7

DHCR24+ tumor epithelial cells drive cisplatin resistance in bladder cancer by enhancing cholesterol metabolism to activate lipid raft-associated MAPK signaling
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