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PRXL2B facilitates the progression of hepatocellular carcinoma and the therapeutic efficacy of oncolytic adenovirus H101 through the PI3K/AKT/PD-L1 axis

Biosci Trends. 2026 May 21. doi: 10.5582/bst.2026.01000. Online ahead of print.

ABSTRACT

Oncolytic adenovirus H101 has shown antitumor activity in hepatocellular carcinoma (HCC), but the molecular determinants of treatment response remain unclear. In this study, a Hepa1-6 subcutaneous tumor model was established in C57BL/6 mice and treated with intratumoral H101, followed by integrated transcriptomic and proteomic analyses to identify candidate genes associated with H101 response. PRXL2B was selected for further investigation using public multi-omics datasets, tissue microarray-based immunohistochemistry, in vitro functional assays, mechanistic analyses, and in vivo validation experiments. Integrated multi-omics analyses identified PRXL2B as a candidate gene downregulated after H101 treatment. Public datasets and tissue-based validation further showed that PRXL2B was upregulated in HCC tissues. In MHCC97H and HCCLM3 cells, PRXL2B knockdown inhibited proliferation, migration, and invasion, promoted apoptosis and cell-cycle arrest, and enhanced the antitumor effect of H101. Mechanistically, PRXL2B silencing reduced AKT phosphorylation and PD-L1 expression. In vivo, PRXL2B knockdown suppressed tumor growth, and the combination of PRXL2B knockdown and H101 produced the strongest antitumor effect. These findings indicate that PRXL2B promotes malignant phenotypes in HCC and may modulate H101 efficacy through the PI3K/AKT/PD-L1 axis. Targeting PRXL2B may therefore represent a potential strategy to enhance the therapeutic efficacy of oncolytic virus therapy in HCC.

PMID:42161529 | DOI:10.5582/bst.2026.01000

Stabilizing Unsupervised Self-Evolution of MLLMs via Continuous Softened Retracing reSampling

arXiv:2604.03647v1 Announce Type: cross Abstract: In the unsupervised self-evolution of Multimodal Large Language Models, the quality of feedback signals during post-training is pivotal for stable and effective learning. However, existing self-evolution methods predominantly rely on majority voting to select the most frequent output as the pseudo-golden answer, which may stem from the model's intrinsic biases rather than guaranteeing the objective correctness of the reasoning paths. To counteract the degradation, we propose \textbf{C}ontinuous \textbf{S}oftened \textbf{R}etracing re\textbf{S}ampling (\textbf{CSRS}) in MLLM self-evolution. Specifically, we introduce a Retracing Re-inference Mechanism (\textbf{RRM}) that the model re-inferences from anchor points to expand the exploration of long-tail reasoning paths. Simultaneously, we propose Softened Frequency Reward (\textbf{SFR}), which replaces binary rewards with continuous signals, calibrating reward based on the answers' frequency across sampled reasoning sets. Furthermore, incorporated with Visual Semantic Perturbation (\textbf{VSP}), CSRS ensures the model prioritizes mathematical logic over visual superficiality. Experimental results demonstrate that CSRS significantly enhances the reasoning performance of Qwen2.5-VL-7B on benchmarks such as MathVision. We achieve state-of-the-art (SOTA) results in unsupervised self-evolution on geometric tasks. Our code is avaible at https://github.com/yyy195/CSRS.

When Models Judge Themselves: Unsupervised Self-Evolution for Multimodal Reasoning

arXiv:2603.21289v2 Announce Type: replace-cross Abstract: Recent progress in multimodal large language models has led to strong performance on reasoning tasks, but these improvements largely rely on high-quality annotated data or teacher-model distillation, both of which are costly and difficult to scale. To address this, we propose an unsupervised self-evolution training framework for multimodal reasoning that achieves stable performance improvements without using human-annotated answers or external reward models. For each input, we sample multiple reasoning trajectories and jointly model their within group structure. We use the Actor's self-consistency signal as a training prior, and introduce a bounded Judge based modulation to continuously reweight trajectories of different quality. We further model the modulated scores as a group level distribution and convert absolute scores into relative advantages within each group, enabling more robust policy updates. Trained with Group Relative Policy Optimization (GRPO) on unlabeled data, our method consistently improves reasoning performance and generalization on five mathematical reasoning benchmarks, offering a scalable path toward self-evolving multimodal models. The code are available at https://github.com/OPPO-Mente-Lab/LLM-Self-Judge.
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