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Received — 10 September 2026 ⏭

S1P-TREM2 axis protects immunosuppressive neutrophils from ferroptosis to promote tumour progression in hepatocellular carcinoma

✇Omics in Hepatocellular
By: Jun Ma · Tong Wu · Diyu Chen · Can Zhu · Shanhe Huang · Keyi Du · Chuanhui Peng · Junru Chen · Yunhao Chen · Haiyang Xie · Feng Zhang · Jianzhong Chen · Shusen Zheng · Jian Wu
7 September 2026 at 18:00

Gut. 2026 Sep 7:gutjnl-2025-337414. doi: 10.1136/gutjnl-2025-337414. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood.

OBJECTIVE: To elucidate the metabolic and molecular programmes that enable tumour-associated neutrophils (TANs) to resist ferroptosis and sustain immunosuppression in HCC.

DESIGN: We employed human HCC samples, multiple murine HCC models, transcriptomic and lipidomic profiling, genetic loss-of-function systems and therapeutic interventions. Ferroptosis sensitivity, lipid metabolic rewiring and immunological consequences of TANs were systematically evaluated across models and validated in patient datasets and biospecimens.

RESULTS: TANs in human HCC and mouse models exhibit pronounced lipid accumulation and oxidative stress compared with peripheral neutrophils. Multi-omic profiling revealed that TANs are enriched for lipid-binding gene programmes and undergo rewiring towards sphingolipid and unsaturated fatty acid metabolism. We identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key lipid-sensing receptor selectively expressed in TANs. Functional deletion of TREM2 reprogrammed the tumour immune microenvironment, restoring CD8+ T cell activity and suppressing HCC progression. Mechanistically, tumour-derived sphingosine-1-phosphate (S1P) activates TREM2, triggering nuclear factor erythroid 2-related factor 2 (NRF2)-mediated transcription of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), thereby promoting ferroptosis resistance. TREM2 expression is transcriptionally induced by granulocyte-macrophage colony-stimulating factor-signal transducer and activator of transcription 3 (GM-CSF-STAT3) signalling. Genetic deletion of TREM2, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout of sphingosine kinase 1/2 (SPHK1/2) in tumour cells, or pharmacological inhibition of S1P synthesis disrupts this protective lipid-immune circuit, sensitises TANs to ferroptosis and restricts tumour growth. Therapeutically, a peptide-based TREM2 inhibitor reprogrammes TANs, restores CD8+ T cell function and enhances anti-programmed cell death protein 1 (PD-1) immunotherapy efficacy. Clinically, TREM2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in HCC tumours, correlate with SPHK1/2 expression and T cell dysfunction and associate with poor patient prognosis.

CONCLUSION: Our study uncovers the S1P-TREM2-NRF2 axis as a critical metabolic-immune circuit that preserves neutrophil survival and immunosuppressive function in HCC. Targeting this lipid-dependent ferroptosis resistance pathway offers a promising therapeutic strategy to overcome immunotherapy resistance in liver cancer.

PMID:42705697 | DOI:10.1136/gutjnl-2025-337414

S1P-TREM2 axis protects immunosuppressive neutrophils from ferroptosis to promote tumour progression in hepatocellular carcinoma

✇(Multiomics OR Omics) AND (Pancreatic)
By: Jun Ma · Tong Wu · Diyu Chen · Can Zhu · Shanhe Huang · Keyi Du · Chuanhui Peng · Junru Chen · Yunhao Chen · Haiyang Xie · Feng Zhang · Jianzhong Chen · Shusen Zheng · Jian Wu
7 September 2026 at 18:00

Gut. 2026 Sep 7:gutjnl-2025-337414. doi: 10.1136/gutjnl-2025-337414. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood.

OBJECTIVE: To elucidate the metabolic and molecular programmes that enable tumour-associated neutrophils (TANs) to resist ferroptosis and sustain immunosuppression in HCC.

DESIGN: We employed human HCC samples, multiple murine HCC models, transcriptomic and lipidomic profiling, genetic loss-of-function systems and therapeutic interventions. Ferroptosis sensitivity, lipid metabolic rewiring and immunological consequences of TANs were systematically evaluated across models and validated in patient datasets and biospecimens.

RESULTS: TANs in human HCC and mouse models exhibit pronounced lipid accumulation and oxidative stress compared with peripheral neutrophils. Multi-omic profiling revealed that TANs are enriched for lipid-binding gene programmes and undergo rewiring towards sphingolipid and unsaturated fatty acid metabolism. We identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key lipid-sensing receptor selectively expressed in TANs. Functional deletion of TREM2 reprogrammed the tumour immune microenvironment, restoring CD8+ T cell activity and suppressing HCC progression. Mechanistically, tumour-derived sphingosine-1-phosphate (S1P) activates TREM2, triggering nuclear factor erythroid 2-related factor 2 (NRF2)-mediated transcription of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), thereby promoting ferroptosis resistance. TREM2 expression is transcriptionally induced by granulocyte-macrophage colony-stimulating factor-signal transducer and activator of transcription 3 (GM-CSF-STAT3) signalling. Genetic deletion of TREM2, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout of sphingosine kinase 1/2 (SPHK1/2) in tumour cells, or pharmacological inhibition of S1P synthesis disrupts this protective lipid-immune circuit, sensitises TANs to ferroptosis and restricts tumour growth. Therapeutically, a peptide-based TREM2 inhibitor reprogrammes TANs, restores CD8+ T cell function and enhances anti-programmed cell death protein 1 (PD-1) immunotherapy efficacy. Clinically, TREM2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in HCC tumours, correlate with SPHK1/2 expression and T cell dysfunction and associate with poor patient prognosis.

CONCLUSION: Our study uncovers the S1P-TREM2-NRF2 axis as a critical metabolic-immune circuit that preserves neutrophil survival and immunosuppressive function in HCC. Targeting this lipid-dependent ferroptosis resistance pathway offers a promising therapeutic strategy to overcome immunotherapy resistance in liver cancer.

PMID:42705697 | DOI:10.1136/gutjnl-2025-337414

Received — 27 May 2026 ⏭

Nonlinear atomic tunnelling boosted by bright squeezed vacuum

✇Nature - Issue - nature.com science feeds
By: Zhejun Jiang · Shengzhe Pan · Jianqi Chen · Mingyu Zhu · Chenhao Zhao · Yiwen Wang · Ru Zhang · Jianshi Lu · Lulu Han · Suwen Xiong · Dian Wu · Wenxue Li · Shicheng Jiang · Hongcheng Ni · Jian Wu
20 May 2026 at 08:00

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10485-9

Bright squeezed vacuum light boosts nonlinear atomic tunnelling ionization more than 20-fold compared with coherent light, enabling quantum control of strong-field processes without increasing classical intensity.
Received — 11 March 2026 ⏭

GCGNet: Graph-Consistent Generative Network for Time Series Forecasting with Exogenous Variables

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhengyu Li · Xiangfei Qiu · Yuhan Zhu · Xingjian Wu · Jilin Hu · Chenjuan Guo · Bin Yang
10 March 2026 at 12:00
arXiv:2603.08032v1 Announce Type: cross Abstract: Exogenous variables offer valuable supplementary information for predicting future endogenous variables. Forecasting with exogenous variables needs to consider both past-to-future dependencies (i.e., temporal correlations) and the influence of exogenous variables on endogenous variables (i.e., channel correlations). This is pivotal when future exogenous variables are available, because they may directly affect the future endogenous variables. Many methods have been proposed for time series forecasting with exogenous variables, focusing on modeling temporal and channel correlations. However, most of them use a two-step strategy, modeling temporal and channel correlations separately, which limits their ability to capture joint correlations across time and channels. Furthermore, in real-world scenarios, time series are frequently affected by various forms of noises, underscoring the critical importance of robustness in such correlations modeling. To address these limitations, we propose GCGNet, a Graph-Consistent Generative Network for time series forecasting with exogenous variables. Specifically, GCGNet first employs a Variational Generator to produce coarse predictions. A Graph Structure Aligner then further guides it by evaluating the consistency between the generated and true correlations, where the correlations are represented as graphs, and are robust to noises. Finally, a Graph Refiner is proposed to refine the predictions to prevent degeneration and improve accuracy. Extensive experiments on 12 real-world datasets demonstrate that GCGNet outperforms state-of-the-art baselines.
Received — 25 February 2026 ⏭

ST-EVO: Towards Generative Spatio-Temporal Evolution of Multi-Agent Communication Topologies

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xingjian Wu · Xvyuan Liu · Junkai Lu · Siyuan Wang · Xiangfei Qiu · Yang Shu · Jilin Hu · Chenjuan Guo · Bin Yang
24 February 2026 at 13:00
arXiv:2602.14681v2 Announce Type: replace-cross Abstract: LLM-powered Multi-Agent Systems (MAS) have emerged as an effective approach towards collaborative intelligence, and have attracted wide research interests. Among them, ``self-evolving'' MAS, treated as a more flexible and powerful technical route, can construct task-adaptive workflows or communication topologies, instead of relying on a predefined static structue template. Current self-evolving MAS mainly focus on Spatial Evolving or Temporal Evolving paradigm, which only considers the single dimension of evolution and does not fully incentivize LLMs' collaborative capability. In this work, we start from a novel Spatio-Temporal perspective by proposing ST-EVO, which supports dialogue-wise communication scheduling with a compact yet powerful flow-matching based Scheduler. To make precise Spatio-Temporal scheduling, ST-EVO can also perceive the uncertainty of MAS, and possesses self-feedback ability to learn from accumulated experience. Extensive experiments on nine benchmarks demonstrate the state-of-the-art performance of ST-EVO, achieving about 5%--25% accuracy improvement.
Received — 17 February 2026 ⏭

ST-EVO: Towards Generative Spatio-Temporal Evolution of Multi-Agent Communication Topologies

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xingjian Wu · Xvyuan Liu · Junkai Lu · Siyuan Wang · Yang Shu · Jilin Hu · Chenjuan Guo · Bin Yang
17 February 2026 at 13:00
arXiv:2602.14681v1 Announce Type: cross Abstract: LLM-powered Multi-Agent Systems (MAS) have emerged as an effective approach towards collaborative intelligence, and have attracted wide research interests. Among them, ``self-evolving'' MAS, treated as a more flexible and powerful technical route, can construct task-adaptive workflows or communication topologies, instead of relying on a predefined static structue template. Current self-evolving MAS mainly focus on Spatial Evolving or Temporal Evolving paradigm, which only considers the single dimension of evolution and does not fully incentivize LLMs' collaborative capability. In this work, we start from a novel Spatio-Temporal perspective by proposing ST-EVO, which supports dialogue-wise communication scheduling with a compact yet powerful flow-matching based Scheduler. To make precise Spatio-Temporal scheduling, ST-EVO can also perceive the uncertainty of MAS, and possesses self-feedback ability to learn from accumulated experience. Extensive experiments on nine benchmarks demonstrate the state-of-the-art performance of ST-EVO, achieving about 5%--25% accuracy improvement.
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