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Break the Brake, Not the Wheel: Untargeted Jailbreak via Entropy Maximization

arXiv:2605.10764v2 Announce Type: replace-cross Abstract: Recent studies show that gradient-based universal image jailbreaks on vision-language models (VLMs) exhibit little or no cross-model transferability, casting doubt on the feasibility of transferable multimodal jailbreaks. We revisit this conclusion under a strictly untargeted threat model without enforcing a fixed prefix or response pattern. Our preliminary experiment reveals that refusal behavior concentrates at high-entropy tokens during autoregressive decoding, and non-refusal tokens already carry substantial probability mass among the top-ranked candidates before attack. Motivated by this finding, we propose Untargeted Jailbreak via Entropy Maximization(UJEM)-KL, a lightweight attack that maximizes entropy at these decision tokens to flip refusal outcomes, while stabilizing the remaining low-entropy positions to preserve output quality. Across three VLMs and two safety benchmarks, UJEM-KL achieves competitive white-box attack success rates and consistently improves transferability, while remaining effective under representative defenses. Our experimental results indicate that the limited transferability primarily stems from overly constrained optimization objectives.

Kaempferol functionally reprograms CD47 signaling to promote cytoprotection and attenuate oxeiptosis in severe acute pancreatitis

Phytomedicine. 2026 May 15;157:158305. doi: 10.1016/j.phymed.2026.158305. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute pancreatitis (SAP) lacks targeted therapies, and massive loss of functional pancreatic acinar cells (PAC) drives mortality. Kaempferol (KA) possesses well-established anti-inflammatory and cytoprotective activities and is derived from herbal medicinal plants, but its direct molecular targets and mechanism of action in SAP remain undefined.

PURPOSE: To evaluate the protective effects of KA against SAP and to elucidate its molecular mechanism of specific action, with a focus on identifying the direct cellular target through which KA exerts its cytoprotective effects.

STUDY DESIGN: Gain‑/loss‑of‑function in vitro and PAC‑specific CD47 SAP mouse models, combined with multi‑omics screening and biophysical assays.

METHODS: CD47 manipulation (siRNA/overexpression) was performed in primary PACs and cell lines, combined with WT/CD47-/-/Mist1‑CD47‑iOE (PAC‑specific) mouse models. Network pharmacology, transcriptomics and proteomics were integrated to screen and validate KA's protective effects. Computational‑experimental approaches (molecular docking/dynamics, CETSA, SPR, co‑IP, pharmacological epistasis) characterized KA's allosteric modulation of CD47 signaling.

RESULTS: CD47 was upregulated in SAP; its knockout reduced PAC death via KEAP1/PGAM5/AIFM1-driven oxeiptosis. KA reduced PAC death across genotypes, afforded no extra benefit in CD47-KO, and was not overridden by CD47‑OE. Mechanistically, KA allosterically binds CD47 ectodomain, stabilizes the CD47‑ UBQLN1 complex, and redirects signaling from Gαi‑mediated death to Gβγ/ ERK/NRF2‑mediated survival. ERK inhibition attenuated KA's protection. KA's action was CD47‑dependent.

CONCLUSION: This study identifies anti-oxeiptosis as a novel pharmacological activity of KA in SAP. This is achieved through allosteric modulation of CD47, redirecting its signaling from death‑promoting to a protective axis via activating Gβγ/ERK/NRF2 to suppress oxeiptosis. These findings reveal the CD47‑oxeiptosis axis as a therapeutic target and position KA as a promising candidate for SAP therapy, adding a new mechanistic dimension to KA's known pharmacological profile.

PMID:42184499 | DOI:10.1016/j.phymed.2026.158305

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