Immune-related biomarkers in liquid biopsy for cancer: emerging tools for non-invasive precision oncology

MRD

By: Lai Wen · Xinhui Wang · Jinming Liu · Xinxin Pan · Yixin Zhang · Shuang Li · Mengying Tong · Yuankuan Jiang · Hewen Guan

29 September 2026 at 18:00

Front Cell Dev Biol. 2026 Sep 14;14:1878092. doi: 10.3389/fcell.2026.1878092. eCollection 2026.

ABSTRACT

Liquid biopsy has emerged as a powerful non-invasive tool in precision oncology, providing real-time insights into tumor evolution, host immune responses, and dynamic changes in the tumor immune microenvironment. By enabling minimally invasive sampling, it can overcome several limitations of conventional tissue biopsy. This review summarizes the major biological sources and components of liquid biopsy, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and circulating immune cells, and discusses their value as dynamic indicators of interactions during cancer immunotherapy. Particular attention is given to immune-related biomarkers associated with immune checkpoints, immunosuppressive mechanisms, and immune escape, including circulating immune cell populations, and inflammatory cytokine profiles. We further examine their potential applications in predicting treatment response, monitoring immune-related adverse events, assessing minimal residual disease, and detecting acquired resistance. In addition, recent technological advances that are accelerating the clinical translation of liquid biopsy are highlighted, including multi-omics integration, microfluidic platforms. These approaches have improved the sensitivity, accuracy, and multidimensional characterization of tumor- and immune-derived biomarkers. Nevertheless, biological heterogeneity, limited assay standardization, and the lack of large-scale prospective validation studies continue to restrict widespread clinical implementation. Overall, immune-related biomarkers detected through liquid biopsy offer considerable potential for the longitudinal monitoring of the tumor immune microenvironment and may improve non-invasive cancer diagnosis, therapeutic monitoring, and personalized immunotherapy in the era of precision oncology.

PMID:42807637 | PMC:PMC13617286 | DOI:10.3389/fcell.2026.1878092

ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway

Cell Death Discovery nature.com science feeds

By: Xiaoting Chen · Xujie Zhou · Yuting Sang · Zehao Wang · Yue Zhou · Zhishuang Gao · Yanhui Wang · Yangsiyuan Zhao · Rui Xu · Bingqiu Xiu · Jingyan Xue · Jiong Wu

16 September 2026 at 08:00

Cell Death Discovery, Published online: 16 September 2026; doi:10.1038/s41420-026-03349-8

ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway

The Anatomy and Boundary of Adaptation under Temporal Tabular Shift

cs.AI, q-bio.NC updates on arXiv.org

By: Tianyu Wang · Xi Vincent Wang · Lihui Wang · Mian Li · Zhihao Liu

14 September 2026 at 12:00

arXiv:2609.12136v1 Announce Type: cross Abstract: Prequential adaptation of frozen tabular foundation models under temporal drift, with each label revealed only after prediction, helps some deployments and harms others, yet current practice does not predict which. We study the sources and limits of these gains. A diagnostic anatomy attributes gains to four recurring mechanisms under a streaming protocol that removes three optimistic biases and quantifies a fourth. Within an agnostic total-variation drift class, the target conditional is only partially identified: its identified-set diameter, the \emph{wall}, is irreducible from unlabeled data uniformly in sample size. A second, orthogonal $L^2$ projection wall quantifies what the frozen representation cannot express. Two canonical mechanism priors collapse the first wall. Under stated nuisance-rate conditions, the wall can be estimated from labeled historical windows at a $\sqrt N$ rate above the margin threshold $\gamma^\star=d_0/(2\alpha_s)$. At $\gamma=0$, the conditional lower-bound program depends on an open affinity estimate; the positive-margin lower branch also remains open. Semi-synthetic data illustrate the finite-sample mechanism with calibrated exponents. Stream-level proxies on eight industrial streams fall on the difficult side under a stated roughness bound, while the equality case $\gamma=\gamma^\star$ remains unresolved.

SCOPE-OPSD: Fisher-Conditioned Privileged Subspaces for On-Policy Self-Distillation

arXiv:2609.12579v1 Announce Type: cross Abstract: On-policy self-distillation (OPSD) scores student-generated prefixes with a solution-conditioned self-teacher, yet transfers supervision only through next-token probabilities. We ask whether the aligned final-layer discrepancy offers a useful second channel, and how to test that channel without confusing its geometry with auxiliary strength. SCOPE-OPSD projects the privileged teacher-student residual onto a frozen rank-64 factor estimated from residual covariance and language-model-head Fisher sensitivity. It reuses the forwards already required by OPSD and adds neither rollouts nor inference-time modules. A matched Random control preserves the structured factor's rank and nonzero spectrum and uses per-arm gradient-RMS calibration, isolating the effect of the data-dependent orientation. Across the complete 25/50/75/100-step trajectories for Qwen3-1.7B, 4B, and 8B, Structured is never below Pure OPSD, with strict gains in 11 of the 12 model-checkpoint combinations and an exact tie at 4B step 25. Structured also exceeds matched Random in 10 of the 12 combinations. At step 75 on Qwen3-1.7B, Structured exceeds matched Random by 1.39 Macro Avg@12 points in each of two independent training reruns. A cross-fitted diagnostic also shows 4.40 times greater held-out privileged-gap capture than the matched random orientation. The results support a compact, Fisher-conditioned privileged subspace for short-budget OPSD.

Hepatic Usp2 orchestrates de novo lipogenesis through G3bp2 stabilization and β-catenin activation

Cell Death Discovery nature.com science feeds

By: Wei Wang · Hui Wang · Yihan Liu · Siyuan Cui · Chuanxi Tang · Mengxue Wang · Chunyan Mu · Jingyu Li · Xianlong Ye · Xinmiao Liang · Shenglong Zhu

14 September 2026 at 08:00

Cell Death Discovery, Published online: 14 September 2026; doi:10.1038/s41420-026-03333-2

Hepatic Usp2 orchestrates de novo lipogenesis through G3bp2 stabilization and β-catenin activation

Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine

Omics In Lung

By: Wenbo Hu · Xuehui Wang

12 September 2026 at 18:00

Front Pharmacol. 2026 Aug 28;17:1899849. doi: 10.3389/fphar.2026.1899849. eCollection 2026.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

PMID:42729333 | PMC:PMC13561894 | DOI:10.3389/fphar.2026.1899849

Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Wenbo Hu · Xuehui Wang

12 September 2026 at 18:00

Front Pharmacol. 2026 Aug 28;17:1899849. doi: 10.3389/fphar.2026.1899849. eCollection 2026.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

PMID:42729333 | PMC:PMC13561894 | DOI:10.3389/fphar.2026.1899849

A clinically-oriented foundation model for intraoperative pathology

Nature Medicine

By: Zihan Zhao · Fengtao Zhou · Ronggang Li · Bing Chu · Xinke Zhang · Xueyi Zheng · Ke Zheng · Xiaobo Wen · Jiabo Ma · Yihui Wang · Jiewei Chen · Chengyou Zheng · Jiangyu Zhang · Yongqin Wen · Jiajia Meng · Ziqi Zeng · Xiaoqing Li · Jing Li · Dan Xie · Yaping Ye · Yu Wang · Hao Chen · Muyan Cai

10 September 2026 at 08:00

Nature Medicine, Published online: 10 September 2026; doi:10.1038/s41591-026-04703-0

CRISP, a vision-based pathology foundation model developed exclusively from frozen section slides, supports treatment decision-making throughout the surgical workflow with superior performance to current foundation models and extensive validation, including in a prospective cohort.

UnitBoost: Managing Compound LLM Systems with a Merge Operator, Not a Model

cs.AI, q-bio.NC updates on arXiv.org

By: Xing Zhang · Guanghui Wang · Yanwei Cui · Mengdie Flora Wang · Peiyang He

10 September 2026 at 12:00

arXiv:2609.09815v1 Announce Type: new Abstract: Compound LLM systems often solve a coordination problem by adding a higher-level LLM. The resulting meta-agent reads workers' outputs, writes the final answer, allocates later calls, and decides when to stop. It is expressive, but it also concentrates three control decisions in an opaque, order-sensitive model call. We ask whether the manager needs to be generative at all. UnitBoost replaces that model with a defined meta-level operator: a task-given unit map turns worker outputs into slot-value proposals, a constrained argmax assembles the output, and the slots left unfilled or unsupported become an explicit residual for the next round. The operator is order-free, records unit provenance, and gives a simple guarantee: without coupling constraints, unit-wise maximization under the same admission score dominates selection of any complete candidate. On three held-out benchmarks, it exceeds the best single candidate chosen with gold labels by 0.060-0.195 absolute task-score points and input-matched generative managers by 0.048-0.076. Replacing only the management step improves six compound-system configurations by 0.013-0.182. Residual-directed rounds raise FanOutQA cell F1 from 0.4778 to 0.5524; matched controls show that the true residual outperforms random targets and ordinary rereading, while a label-free supply signal flags exhaustion after one unproductive round. The same analysis measures three conditions in which no such gain is available (one indivisible unit, unavailable unit identity, and an endpoint that charges for every emitted unit) and quantifies cross-unit coupling as a repair cost. The manager gives up semantic freedom and gains order invariance, unit provenance, and testable failure conditions.

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

Cell

By: Han Shi · E. Andrew Bennett · Guoke Chen · Hui Wang · Tianyi Wang · Peng Cao · Ruilin Mao · Fan Bai · Qingyan Dai · Feng Liu · Xiaotian Feng · Yongan Wang · Chong Yao · Jing Wu · Wenjun Wang · Ming Zhang · Tianxiang Liu · Jingkun Ran · Yue-Chen Liu · Yuan Liu · Dan Ju · Chuyan Li · Hongwei Hou · Xinyi Liu · Qiaomei Fu

3 September 2026 at 08:00

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.

Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer

Cell

By: YaTing Wen · LingJie Tang · WenWen Duan · QingFei Ren · YangYue Ni · ShiYang Chen · Jun Chen · Lei Yang · Huan Wang · Yuan Chen · YunZhe Zheng · XingChao Pan · Hui Du · MengWen Huang · An Zeng · Zhaocai Zhou · ZhiGang Zhang · HongBin Ji · GaoXiang Ge · Yi Arial Zeng · Wei Zhang · ShiHui Wang · JianJun Cheng · Sheng Wang · JianFeng Chen

4 August 2026 at 08:00

By selectively targeting peripheral 5-HT2AR without inducing psychedelic effects, a non-brain-penetrant agonist boosts antitumor CD8+ T cell immunity and improves immunotherapy responses in preclinical models of colorectal cancer.

MindAlign: Bridging EEG, Vision, and Language for Zero-Shot Visual Decoding

cs.AI, q-bio.NC updates on arXiv.org

By: Zexuan Chen · Sichao Liu · Runhao Lu · Huichao Qi · Alexandra Woolgar · Xi Vincent Wang · Lihui Wang

26 May 2026 at 12:00

arXiv:2605.24523v1 Announce Type: cross Abstract: Visual decoding from brain signals is a key challenge at the intersection of computer vision and neuroscience, requiring methods that bridge neural representations and computational models of vision. We introduce a tri-modal contrastive framework for EEG-based visual decoding that aligns EEG, visual, and textual representations within a unified latent space. Our approach follows a two-stage design. First, we pre-train an EEG encoder via masked reconstruction on unlabeled trials, learning spatio-temporal regularities that transfer robustly to downstream tasks. Second, we jointly align EEG, image, and LLM-generated textual descriptions through contrastive learning, where text supervision acts as a semantic regularizer that injects linguistic structure into the shared space without overwhelming the primary EEG-image signal. The encoder integrates subject-specific adaptation, graph-attention over channels, and temporal-spatial convolutional embeddings. On the Things-EEG2 200-way zero-shot benchmark, our framework achieves 54.1% Top-1 and 83.4% Top-5 accuracy, substantially exceeding the strongest prior baseline (32.4% / 64.0%), with paired Wilcoxon tests confirming significance (p

What Are We Actually Decoding? Source Attribution for Non-Invasive Brain-to-Language Retrieval

cs.AI, q-bio.NC updates on arXiv.org

By: Xinyu Zhang · Sichao Liu · Runhao Lu · Alexandra Woolgar · Lihui Wang

26 May 2026 at 12:00

arXiv:2605.24524v1 Announce Type: cross Abstract: In non-invasive neural language decoding, results can be inflated by sources that are not stimulus-evoked neural evidence: decoder priors, embedding-based metrics, and non-neural structural nuisances such as signal duration. The methodological challenge is therefore attribution: a reported gain is more informative when it can be traced to a specific source. We recast stimulus-locked MEG-to-audio retrieval as an auditing framework that separates apparent performance into three sources - structural shortcuts, window-level stimulus-locked evidence, and cross-window contextual aggregation - and provides a diagnostic for each. Signal-blind Gaussian noise reaches 66.3% Rank@1 (R@1) under variable-length decoding but collapses to near chance once fixed-duration windows and stimulus-identity splits are enforced, isolating structural leakage. Under these controls, fixed-window retrieval recovers measurable MEG-audio discriminability, while an oracle sentence-bucket diagnostic shows that 95.7% of Top-1 errors select the wrong sentence, localising the residual bottleneck to sentence-level competition. We audit this contextual source with Group Context Bias (GCB), an inference-time additive logit bias that pools sentence-consistent evidence across windows while leaving the base retrieval scores and candidate pool fixed. Used as a score-space intervention, GCB makes the contextual source measurable: R@1 shifts from 44% to 52% on Gwilliams and from 22% to 29% on MOUS under the same fixed setting. GCB is auditable under this design: its effect collapses under random-grouping perturbations and vanishes when local evidence is attenuated in MEG or is near chance in EEG, supporting its use as a controlled source-attribution intervention. These results suggest that brain-to-language performance should be source-attributed, not merely reported.

Multi-omics Analysis Reveals the Protection of a Quadruple Probiotic Mixture in Experimental Autoimmune Hepatitis

(Multiomics OR Omics) AND (Pancreatic)

By: Yu Chen · Shuhui Wang · Anzhuo Chen · Zhuoying Lin · Han Wang · Wanneng Li · Jun Liu · Jia Yao · Dean Tian · Yu Lei · Mei Liu

23 May 2026 at 18:00

Probiotics Antimicrob Proteins. 2026 May 23. doi: 10.1007/s12602-026-11062-2. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease with a rising global incidence. The treatment of AIH remains challenging because first-line drugs show limited efficacy and systemic side effects. Gut microbiota plays a crucial role in the pathogenesis of AIH, leading to growing interest in developing probiotic-based therapies. In this study, we used multi-omics analysis to investigate the therapeutic effects of a quadruple probiotic mixture (Probiotic-quad) consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus in a well-established chronic AIH murine model. Our results showed that Probiotic-quad treatment significantly alleviated AIH progression, as evidenced by lower serum liver enzyme levels, ameliorated hepatic inflammatory infiltration and histopathological damage. Metagenomic sequencing results showed that gut dysbiosis in AIH mice was partially reversed after Probiotic-quad administration. Additionally, the integrity of the intestinal epithelial barrier was restored, accompanied by a reduction in serum lipopolysaccharide levels. Untargeted metabolomic and transcriptomic analysis revealed that Probiotic-quad treatment was linked to alterations in hepatic metabolism, including the citrate cycle and tryptophan metabolism, and was associated with reduced activation of the NF-κB and NOD-like receptor signaling pathways. These findings suggest that Probiotic-quad treatment ameliorates AIH severity and is potentially associated with changes in hepatic immune responses, metabolism, gut microbiota, and intestinal barrier function, highlighting its potential as an adjuvant therapy for AIH.

PMID:42176246 | DOI:10.1007/s12602-026-11062-2

CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells

Nature Cancer

By: Chaoxiong Wang · Peixuan Zheng · Anhui Wang · Xinrui Fan · Tianxiang Li · Jingjing Hong · Runze Wang · Chunyan Zhang · Chaogui Luo · Weiwei Yang · Dong Gao · Adili Salai · Min Luo · Zhigang Lu · Dianfan Li · Moubin Lin · Jiayin Peng · Guohui Li · Shuo Han · Yun Zhao

15 May 2026 at 08:00

Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4

Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.

Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures

Cell

By: Him K. Shrestha · Huan Sun · Jay M. Yarbro · DongGeun Lee · Danting Liu · Erming Wang · Meghan McReynolds · Nan Zhang · Boer Xie · Shu Yang · Kaiwen Yu · Suresh Poudel · Yuxin Li · Zuo-Fei Yuan · Dehui Kong · Minghui Wang · Zhen Wang · Mingming Niu · Hong Wang · Masihuz Zaman · Ju Wang · David R. Vanderwall · Yu Sun · Zhiping Wu · Ping-Chung Chen · Bing Bai · Anthony A. High · Júlia Faura · Chunyu Liu · David A. Bennett · Erik C.B. Johnson · Nicholas T. Seyfried · Allan I. Levey · Vahram Haroutunian · Geidy E. Serrano · Thomas G. Beach · Michael DeTure · Takahisa Kanekiyo · Ronald C. Petersen · Guojun Bu · Pamela J. McLean · Dennis W. Dickson · Rosa Rademakers · Gang Yu · Xusheng Wang · Bin Zhang · Junmin Peng

23 March 2026 at 08:00

A pan-neurodegeneration atlas built from multilayer, deep proteomics of 2,279 brain samples across 6 major diseases integrates whole proteome, detergent-insoluble proteome, and posttranslational modifications to enable intra- and inter-disease comparisons to reveal disease-specific subtypes and dysregulated pathways, while identifying shared changes such as GPNMB upregulation and NPTX2 downregulation.

BAAI Cardiac Agent: An intelligent multimodal agent for automated reasoning and diagnosis of cardiovascular diseases from cardiac magnetic resonance imaging

cs.AI, q-bio.NC updates on arXiv.org

By: Taiping Qu · Hongkai Zhang · Lantian Zhang · Can Zhao · Nan Zhang · Hui Wang · Zhen Zhou · Mingye Zou · Kairui Bo · Pengfei Zhao · Xingxing Jin · Zixian Su · Kun Jiang · Huan Liu · Yu Du · Maozhou Wang · Ruifang Yan · Zhongyuan Wang · Tiejun Huang · Lei Xu · Henggui Zhang

7 April 2026 at 12:00

arXiv:2604.04078v1 Announce Type: cross Abstract: Cardiac magnetic resonance (CMR) is a cornerstone for diagnosing cardiovascular disease. However, it remains underutilized due to complex, time-consuming interpretation across multi-sequences, phases, quantitative measures that heavily reliant on specialized expertise. Here, we present BAAI Cardiac Agent, a multimodal intelligent system designed for end-to-end CMR interpretation. The agent integrates specialized cardiac expert models to perform automated segmentation of cardiac structures, functional quantification, tissue characterization and disease diagnosis, and generates structured clinical reports within a unified workflow. Evaluated on CMR datasets from two hospitals (2413 patients) spanning 7-types of major cardiovascular diseases, the agent achieved an area under the receiver-operating-characteristic curve exceeding 0.93 internally and 0.81 externally. In the task of estimating left ventricular function indices, the results generated by this system for core parameters such as ejection fraction, stroke volume, and left ventricular mass are highly consistent with clinical reports, with Pearson correlation coefficients all exceeding 0.90. The agent outperformed state-of-the-art models in segmentation and diagnostic tasks, and generated clinical reports showing high concordance with expert radiologists (six readers across three experience levels). By dynamically orchestrating expert models for coordinated multimodal analysis, this agent framework enables accurate, efficient CMR interpretation and highlights its potentials for complex clinical imaging workflows. Code is available at https://github.com/plantain-herb/Cardiac-Agent.

ATLAS: A Layered Constraint-Guided Framework for Structured Artifact Generation in LLM-Assisted MDE

cs.AI, q-bio.NC updates on arXiv.org

By: Tong Ma · Hui Lai · Hui Wang · Zhenhu Tian · Chaochao Li · Fengjie Xu · Ling Fang

7 April 2026 at 12:00

arXiv:2510.25890v3 Announce Type: replace-cross Abstract: ATLAS is a constraint-guided generation framework for structured engineering artifacts whose outputs must satisfy explicit schemas, domain rules, and audit requirements. Rather than treating a large language model as a standalone generator, ATLAS places generation inside a model-driven workflow that separates domain representation, constraint compilation, and post-generation validation. ATLAS combines three components. A metamodel-integration stage builds a typed representation of domain entities and relations; in this study, it operates over authoritative AUTOSAR meta-model assets. An Integrated Constraint Model (ICM) compiles heterogeneous requirements into two operational layers: generation-time structural constraints and post-generation semantic/logical obligations. Constraint-Guided, Validation-Backed Generation (CVG) then combines Layer~1 constrained decoding, Layer~2 backend validation, and audit-guided repair. In the AUTOSAR instantiation, these Layer~2 obligations are realized through SHACL/SMT-style checks, illustrating how the same ICM can be connected to domain-specific validation backends. We evaluate ATLAS on AUTOSAR artifact generation at both single-file and multi-file scales. In the evaluated AUTOSAR setting, ATLAS consistently produces schema-valid single-file outputs and preserves perfect file completeness and XSD validity at multi-file scale, while SHACL/SMT checks and result analysis continue to expose residual system-level defects. The empirical picture is therefore one of bounded automation: ATLAS secures structural validity and turns higher-level failures into explicit, diagnosable objects within the generation workflow.

RASA: Routing-Aware Safety Alignment for Mixture-of-Experts Models

cs.AI, q-bio.NC updates on arXiv.org

By: Jiacheng Liang · Yuhui Wang · Tanqiu Jiang · Ting Wang

7 April 2026 at 12:00

arXiv:2602.04448v2 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) language models introduce unique challenges for safety alignment due to their sparse routing mechanisms, which can enable degenerate optimization behaviors under standard full-parameter fine-tuning. In our preliminary experiments, we observe that naively applying full-parameter safety fine-tuning to MoE models can reduce attack success rates through routing or expert dominance effects, rather than by directly repairing Safety-Critical Experts. To address this challenge, we propose RASA, a routing-aware expert-level alignment framework that explicitly repairs Safety-Critical Experts while preventing routing-based bypasses. RASA identifies experts disproportionately activated by successful jailbreaks, selectively fine-tunes only these experts under fixed routing, and subsequently enforces routing consistency with safety-aligned contexts. Across two representative MoE architectures and a diverse set of jailbreak attacks, RASA achieves near-perfect robustness, strong cross-attack generalization, and substantially reduced over-refusal, while preserving general capabilities on benchmarks such as MMLU, GSM8K, and TruthfulQA. Our results suggest that robust MoE safety alignment benefits from targeted expert repair rather than global parameter updates, offering a practical and architecture-preserving alternative to prior approaches.

HISA: Efficient Hierarchical Indexing for Fine-Grained Sparse Attention

cs.AI, q-bio.NC updates on arXiv.org

By: Yufei Xu · Fanxu Meng · Fan Jiang · Yuxuan Wang · Ruijie Zhou · Zhaohui Wang · Jiexi Wu · Zhixin Pan · Xiaojuan Tang · Wenjie Pei · Tongxuan Liu · Di Yin · Xing Sun · Muhan Zhang

7 April 2026 at 12:00

arXiv:2603.28458v3 Announce Type: replace-cross Abstract: Token-level sparse attention mechanisms, exemplified by DeepSeek Sparse Attention (DSA), achieve fine-grained key selection by scoring every historical key for each query through a lightweight indexer, then computing attention only on the selected subset. While the downstream sparse attention itself scales favorably, the indexer must still scan the entire prefix for every query, introducing an per-layer bottleneck that grows prohibitively with context length. We propose HISA (Hierarchical Indexed Sparse Attention), a plug-and-play replacement for the indexer that rewrites the search path from a flat token scan into a two-stage hierarchical procedure: (1) a block-level coarse filtering stage that scores pooled block representations to discard irrelevant regions, followed by (2) a token-level refinement stage that applies the original indexer exclusively within the retained candidate blocks. HISA preserves the identical token-level top-sparse pattern consumed by the downstream Sparse MLA operator and requires no additional training. On kernel-level benchmarks, HISA achieves up to speedup at 64K context. On Needle-in-a-Haystack and LongBench, we directly replace the indexer in DeepSeek-V3.2 and GLM-5 with our HISA indexer, without any finetuning. HISA closely matches the original DSA in quality, while substantially outperforming block-sparse baselines.

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