CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

By: Zhengjian Wang · Zhe Wang · Xuda Ji · Liping Zhao · Kai Zheng · Wen Yu · Hanzhe Zhang · Hong Chang · Fangfeng Liu

25 May 2026 at 18:00

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8⁺ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8⁺ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8⁺ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8⁺ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1⁺ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

Omics in Hepatocellular

By: Zhengjian Wang · Zhe Wang · Xuda Ji · Liping Zhao · Kai Zheng · Wen Yu · Hanzhe Zhang · Hong Chang · Fangfeng Liu

25 May 2026 at 18:00

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8⁺ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8⁺ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8⁺ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8⁺ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1⁺ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

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

By: Zhengjian Wang · Zhe Wang · Xuda Ji · Liping Zhao · Kai Zheng · Wen Yu · Hanzhe Zhang · Hong Chang · Fangfeng Liu

25 May 2026 at 18:00

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8⁺ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8⁺ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8⁺ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8⁺ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1⁺ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

Resource-Conscious Modeling for Next- Day Discharge Prediction Using Clinical Notes

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

By: Ha Na Cho · Sairam Sutari · Alexander Lopez · Hansen Bow · Kai Zheng

7 April 2026 at 12:00

arXiv:2604.03498v1 Announce Type: new Abstract: Timely discharge prediction is essential for optimizing bed turnover and resource allocation in elective spine surgery units. This study evaluates the feasibility of lightweight, fine-tuned large language models (LLMs) and traditional text-based models for predicting next-day discharge using postoperative clinical notes. We compared 13 models, including TF-IDF with XGBoost and LGBM, and compact LLMs (DistilGPT-2, Bio_ClinicalBERT) fine-tuned via LoRA. TF-IDF with LGBM achieved the best balance, with an F1-score of 0.47 for the discharge class, a recall of 0.51, and the highest AUC-ROC (0.80). While LoRA improved recall in DistilGPT2, overall transformer-based and generative models underperformed. These findings suggest interpretable, resource-efficient models may outperform compact LLMs in real-world, imbalanced clinical prediction tasks.

NI-Tex: Non-isometric Image-based Garment Texture Generation

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

By: Hui Shan · Ming Li · Haitao Yang · Kai Zheng · Sizhe Zheng · Yanwei Fu · Xiangru Huang

16 March 2026 at 12:00

arXiv:2511.18765v2 Announce Type: replace-cross Abstract: Existing industrial 3D garment meshes already cover most real-world clothing geometries, yet their texture diversity remains limited. To acquire more realistic textures, generative methods are often used to extract Physically-based Rendering (PBR) textures and materials from large collections of wild images and project them back onto garment meshes. However, most image-conditioned texture generation approaches require strict topological consistency between the input image and the input 3D mesh, or rely on accurate mesh deformation to match to the image poses, which significantly constrains the texture generation quality and flexibility. To address the challenging problem of non-isometric image-based garment texture generation, we construct 3D Garment Videos, a physically simulated, garment-centric dataset that provides consistent geometry and material supervision across diverse deformations, enabling robust cross-pose texture learning. We further employ Nano Banana for high-quality non-isometric image editing, achieving reliable cross-topology texture generation between non-isometric image-geometry pairs. Finally, we propose an iterative baking method via uncertainty-guided view selection and reweighting that fuses multi-view predictions into seamless, production-ready PBR textures. Through extensive experiments, we demonstrate that our feedforward dual-branch architecture generates versatile and spatially aligned PBR materials suitable for industry-level 3D garment design.

RubricBench: Aligning Model-Generated Rubrics with Human Standards

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

By: Qiyuan Zhang · Junyi Zhou · Yufei Wang · Fuyuan Lyu · Yidong Ming · Can Xu · Qingfeng Sun · Kai Zheng · Peng Kang · Xue Liu · Chen Ma

4 March 2026 at 13:00

arXiv:2603.01562v2 Announce Type: replace Abstract: As Large Language Model (LLM) alignment evolves from simple completions to complex, highly sophisticated generation, Reward Models are increasingly shifting toward rubric-guided evaluation to mitigate surface-level biases. However, the community lacks a unified benchmark to assess this evaluation paradigm, as existing benchmarks lack both the discriminative complexity and the ground-truth rubric annotations required for rigorous analysis. To bridge this gap, we introduce RubricBench, a curated benchmark with 1,147 pairwise comparisons specifically designed to assess the reliability of rubric-based evaluation. Our construction employs a multi-dimensional filtration pipeline to target hard samples featuring nuanced input complexity and misleading surface bias, augmenting each with expert-annotated, atomic rubrics derived strictly from instructions. Comprehensive experiments reveal a substantial capability gap between human-annotated and model-generated rubrics, indicating that even state-of-the-art models struggle to autonomously specify valid evaluation criteria, lagging considerably behind human-guided performance.

NI-Tex: Non-isometric Image-based Garment Texture Generation

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

By: Hui Shan · Ming Li · Haitao Yang · Kai Zheng · Sizhe Zheng · Yanwei Fu · Xiangru Huang

24 February 2026 at 13:00

arXiv:2511.18765v1 Announce Type: cross Abstract: Existing industrial 3D garment meshes already cover most real-world clothing geometries, yet their texture diversity remains limited. To acquire more realistic textures, generative methods are often used to extract Physically-based Rendering (PBR) textures and materials from large collections of wild images and project them back onto garment meshes. However, most image-conditioned texture generation approaches require strict topological consistency between the input image and the input 3D mesh, or rely on accurate mesh deformation to match to the image poses, which significantly constrains the texture generation quality and flexibility. To address the challenging problem of non-isometric image-based garment texture generation, we construct 3D Garment Videos, a physically simulated, garment-centric dataset that provides consistent geometry and material supervision across diverse deformations, enabling robust cross-pose texture learning. We further employ Nano Banana for high-quality non-isometric image editing, achieving reliable cross-topology texture generation between non-isometric image-geometry pairs. Finally, we propose an iterative baking method via uncertainty-guided view selection and reweighting that fuses multi-view predictions into seamless, production-ready PBR textures. Through extensive experiments, we demonstrate that our feedforward dual-branch architecture generates versatile and spatially aligned PBR materials suitable for industry-level 3D garment design.

OffSeeker: Online Reinforcement Learning Is Not All You Need for Deep Research Agents

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

By: Yuhang Zhou · Kai Zheng · Qiguang Chen · Mengkang Hu · Qingfeng Sun · Can Xu · Jingjing Chen

24 February 2026 at 13:00

arXiv:2601.18467v2 Announce Type: replace Abstract: Deep research agents have shown remarkable potential in handling long-horizon tasks. However, state-of-the-art performance typically relies on online reinforcement learning (RL), which is financially expensive due to extensive API calls. While offline training offers a more efficient alternative, its progress is hindered by the scarcity of high-quality research trajectories. In this paper, we demonstrate that expensive online reinforcement learning is not all you need to build powerful research agents. To bridge this gap, we introduce a fully open-source suite designed for effective offline training. Our core contributions include DeepForge, a ready-to-use task synthesis framework that generates large-scale research queries without heavy preprocessing; and a curated collection of 66k QA pairs, 33k SFT trajectories, and 21k DPO pairs. Leveraging these resources, we train OffSeeker (8B), a model developed entirely offline. Extensive evaluations across six benchmarks show that OffSeeker not only leads among similar-sized agents but also remains competitive with 30B-parameter systems trained via heavy online RL.

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