Transketolase-like 1 potentiates PD-1 blockade in hepatocellular carcinoma by glycolysis to prime dendritic cell lactylation

By: Hengsong Cao · Tian Huang · Yue Chai · Zhengqing Lu · Shipeng Dai · Danyang Xu · Yanshu He · Na Yu · Yuliang Wang · Ziyuan Liu · Yidong Xia · Jie Zhao · Hongyu Wang · Dawei Rong · Yuchen Xie · Chongyu Wang · Pengyu Chen · Juyue Zhou · Li Liu · Zhuozheng Li · Hanyuan Liu · Xiao Li · Xuehao Wang · Weiwei Tang · Yongxiang Xia

27 September 2026 at 18:00

Signal Transduct Target Ther. 2026 Sep 28;11(1):418. doi: 10.1038/s41392-026-02875-2.

ABSTRACT

Hepatocellular carcinoma (HCC) exhibits a suboptimal response to immune checkpoint blockade (ICB) therapy; to overcome this resistance, we aimed to delineate key immune resistance factors via multi-omics analysis, develop strategies to block their immunosuppressive axes, and engineer a targeted nanosystem to enhance immunotherapy efficacy against PD-1 resistance in HCC. Using transcriptomic and proteomic data from anti-PD-1-treated HCC patients, along with functional validation in murine models and mechanistic molecular and cell biology studies, we identified transketolase-like 1 (TKTL1) as a dual-nature biomarker where overexpression predicted poor baseline prognosis yet enhanced response to ICB. Mechanistically, TKTL1 diverts glucose flux into glycolysis rather than pentose phosphate pathway (PPP), recruiting USP9X to deubiquitinate and stabilize HIF-1α, which upregulates HK2 to amplify glycolytic output and lactate accumulation. This metabolic rewiring orchestrates dual immunosuppressive circuits through HIF-1α-driven CCL4 secretion recruiting PD-L1^high dendritic cells (DCs), coupled with lactate-induced TRIM28^K408 lactylation that stabilizes PD-L1 by blocking ubiquitin-mediated degradation. We engineered a hepatoma-membrane-coated MnO₂ nanosystem (CQLH) co-delivering a TKTL1 inhibitor and lactate oxidase, which disrupted the TKTL1-HIF-1α-HK2 axis, depleted lactate, and reprogrammed the tumor microenvironment, thereby enhanced anti-PD-1 therapy to suppress tumor growth, especially in TKTL1^high tumors. These findings define a critical "TKTL1-glycolysis-lactate-DC" axis driving anti-PD-1 sensitivity in HCC, position TKTL1 as both a potential biomarker for ICB response and a tractable therapeutic target, and demonstrate that the targeted CQLH nanosystem overcomes resistance and enhances anti-PD-1 efficacy, offering a precision immunotherapeutic strategy for TKTL1^high HCC.

PMID:42802226 | PMC:PMC13616917 | DOI:10.1038/s41392-026-02875-2

Advancing cancer detection and treatment using longitudinal routine clinical data

Cell

By: Fei Liu · Kai Wang · Hui Xu · Cheng Tang · Xian Shen · Meihao Wang · Lei Yang · Li Yang · Li Liu · Changxi Hu · Gen Li · Wei Wu · Zixing Zou · Bingzhou Li · Sian Liu · Jin Kang · Jungho Kong · Ting Li · Io Nam Wong · Xiaoying Huang · Gang Chen · Wenyang Lu · Ian Ziyar · Charlotte L. Zhang · Yiwen Sun · Weihong Lin · Caiwen Ou · Manson Fok · Taiwa Hou · Winston Wang · Kanmin Xue · Yun Yin · Hao Zhu · Jonathan Gootenberg · Omar O. Abudayyeh · Michael Karin · Alexandre Loupy · John E.J. Rasko · Trey Ideker · Huiyan Luo · Eric Oermann · Kang Zhang · International Consortium of Digital Twins in Healthcare and Medicine

27 July 2026 at 08:00

Liu et al. develop Oncoformer, a multimodal transformer that reads routine laboratory tests and chest X-rays already collected in everyday care. Across more than 3.6 million individuals, it detects cancer, infers tumor stage, and stratifies treatment response and recurrence risk, pointing toward risk-adapted cancer care built on data already in hand.

CMA-OT: Hierarchical Expert Supervision for Dance-to-Music Generation

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

By: Jinting Wang · Chenxing Li · Dong Yu · Li Liu

14 September 2026 at 12:00

arXiv:2609.13118v1 Announce Type: new Abstract: Dance-to-music (D2M) generation aims to synthesize music that is rhythmically and stylistically aligned with dance videos. A key challenge arises from the semantic mismatch between sparse dance cues, such as rhythm and style, and the dense information required for music composition, including structure, instrumentation, and expressive dynamics. Existing methods typically rely on these sparse cues and supervise only the final audio output, resulting in poorly learned music representations and generated music with limited musicality and structural coherence. To address these issues, we propose Curriculum-guided Multi-scale representation Alignment with scale-aware Optimal Transport (CMA-OT), a novel paradigm that leverages an external music expert to provide hierarchical supervision for the generator's latent features, bridging the semantic gap and enhancing representation learning. To effectively incorporate hierarchical supervision, we introduce a curriculum-guided multi-scale learning strategy that progressively transfers musical knowledge from the expert to the music generator, enabling stable and effective representation learning. Moreover, to accommodate the semantic and structural variations across different expert scales and achieve fine-grained alignment under temporal mismatch, we propose a scale-aware optimal transport alignment mechanism, which models soft correspondences between hierarchical expert representations and the generator's latent features. Extensive experiments on two datasets demonstrate that CMA-OT achieves state-of-the-art performance in rhythmic synchronization, perceptual quality, and overall music generation.

A framework for building a synthetic cell from the SynCell Asia Initiative

Nature Biotechnology - Issue - nature.com science feeds

By: Zhuojun Dai · Wataru Aoki · Pimchai Chaiyen · Matthew Wook Chang · Xixian Chen · Zibo Chen · Byung-Kwan Cho · Nan-Nan Deng · Shishen Du · Jee Loon Foo · Julius Fredens · Meifang Fu · Xiaojun Han · Tomohisa Hasunuma · Norikazu Ichihashi · Nurulfiza Mat Isa · Daisuke Kiga · Dong-Myung Kim · Jongmin Kim · Akihiko Kondo · Yuishin Kosaka · Kobkul Laoteng · Joongoo Lee · Jian Li · Junbai Li · Ming Li · Sierin Lim · Jianbo Liu · Xingguo Liu · Yuan Lu · Nan Luo · Tomoaki Matsuura · Wataru Mizunashi · Yan Qiao · Ahmad Bazli Ramzi · Sang Woo Seo · Yoshihiro Shimizu · Kwanwoo Shin · Liangfei Tian · Wanwipa Vongsangnak · Baojun Wang · Cheng-Cai Zhang · Xian-En Zhang · Guoping Zhao · Bo Zheng · Yaoqi Zhou · Chenli Liu

26 May 2026 at 08:00

Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03153-w

Building a living cell from scratch requires overcoming a bottleneck that has remained unresolved despite decades of progress: orchestrating the spatiotemporal integration of core functional modules. To tackle this barrier, the SynCell Asia Initiative outlines a strategy for developing core functional modules followed by their systems-level integration through the establishment of a centralized, artificial intelligence (AI)-driven biofoundry.

A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence

Nature - Issue - nature.com science feeds

By: Min He · Jia Su · Xiaogang Zhou · Tuo Qi · Jiazheng Wang · Tianxin Zhang · Jinhua Chen · Mawsheng Chern · Youpin Xu · Xiang Lu · Qingqing Hou · Hongrui Liu · Wenfang Huang · Jiawei Liu · Shiying Li · Yunfei Zhu · Xue Chen · Senyu Ran · Han Li · Renju Liu · Mingliang Lei · Guosong Shu · Haicheng Liao · Junjie Yin · Xiaobo Zhu · Yongyan Tang · Li Song · Long Wang · Qing Xiong · Jiali Liu · Yu Bi · Yihua Yang · Hai Qing · Bingtian Ma · Yan Li · Jing Fan · Peng Qin · Yuping Wang · Jianming Wu · Wenming Wang · Shigui Li · Weitao Li · Jing Wang · Xuewei Chen

20 May 2026 at 08:00

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10572-x

A fungal long non-coding RNA from Magnaporthe oryzae translocates into rice cells to sequester a host microRNA that normally represses PKR1, a negative immunity regulator, thereby facilitating infection and revealing a widespread RNA-based pathogen–host interaction mechanism.

Multi-omics integration and Mendelian randomization reveal the mechanisms and experimental validation of curcumin targeting the RXRA-PI3K/AKT axis to enhance cisplatin sensitivity in gastric cancer

Omics in Gastric

By: Xiaoran Sun · Na Wu · Xue Bai · Xiang Zhang · Rui Wang · Shuai Du · Li Liu · Duo Li

1 May 2026 at 18:00

Front Oncol. 2026 Apr 15;16:1791971. doi: 10.3389/fonc.2026.1791971. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aimed to integrate multi-omics analyses with genetic causal inference to identify key genes associated with cisplatin resistance in gastric cancer and to evaluate the potential mechanism by which curcumin enhances cisplatin sensitivity through relevant pathways.

METHODS: Cisplatin resistance-related transcriptomic datasets(GSE14210 and GSE31811) and a gastric cancer single-cell transcriptomic dataset (GSE183904) were obtained from the Gene Expression Omnibus(GEO)database. Differential expression analysis was performed to identify resistance-associated differentially expressed genes(DEGs),followed by GO and KEGG enrichment analyses. Putative curcumin targets were collected and intersected with DEGs to obtain candidate genes. Mendelian randomization (MR) analysis was conducted using the TwoSampleMR framework to evaluate the genetic association between RXRA expression and gastric cancer risk, with robustness and sensitivity analyses based on multiple MR methods. RXRA expression was further evaluated, along with pathway activity assessment using GSEA and GSVA, and molecular docking was performed to explore the potential binding of curcumin to RXRA. In vitro experiments were performed using the cisplatin-resistant gastric cancer cell lineNCI-N87/DDP. Drug effects and chemosensitization under combination treatment were assessed by CCK-8 assays, synergy was evaluated using the combination index(CI),and changes in key proteins in thePI3K/AKT pathway were measured by Western blotting.

RESULTS: A total of 595 DEGs associated with cisplatin resistance were identified. Functional enrichment analyses indicated that these DEGs were mainly involved in extracellular matrix remodeling and adhesion, secretion and vesicular transport, and signaling pathways including PI3K-Akt.The intersection of curcumin targets with DEGs highlighted RXRA as a key candidate gene. MR results indicated that genetically predicted increased RXRA expression was significantly associated with elevated gastric cancer risk (OR = 4.216,95%CI:1.201-14.797,P=0.025). GSEA and GSVA suggested that high RXRA expression was associated with altered activity of pathways related to lysosome, proteasome, oxidative phosphorylation, and the pentose phosphate pathway. Single-cell analysis indicated that RXRA was mainly expressed in tissue stem cells and fibroblasts. Molecular docking predicted a feasible interaction between curcumin and RXRA. In vitro experiments demonstrated that curcumin inhibited the viability of resistant cells and showed a synergistic trend when combined with cisplatin. Western blotting revealed decreased p-PI3K and p-AKT levels following curcumin treatment, supporting an inhibitory effect on the PI3K/AKT pathway.

CONCLUSION: These findings highlight RXRA as a candidate gene associated with cisplatin resistance-related programs in gastric cancer. Curcumin may enhance cisplatin sensitivity by influencing RXRA-associated transcriptional networks and suppressing PI3K/AKT signaling. This study provides new candidate targets and experimental evidence for mechanistic investigation and combination treatment strategies to overcome cisplatin resistance in gastric cancer.

PMID:42063729 | PMC:PMC13124633 | DOI:10.3389/fonc.2026.1791971

Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson’s disease models

Cell

By: Shiwei Du · Qi Long · Yanshuang Zhou · Jiangqin Fu · Hao Wu · Liang Yang · Yaohang Xie · Yingzhe Ding · Maolei Zhang · Jingyi Guo · Mengfei Wang · Jiajun Lin · Mingli Hu · Jian Zhang · Deyang Yao · Wei Li · Feixiang Bao · Ge Xiang · Yi Wu · Yile Huang · Haozhao Liang · Rui Wang · Heying Li · Baodan Chen · Chong Li · Junwei Wang · Jiwei Zhang · Dajiang Qin · Jianwei Sun · Yun Zhu · Fei Sun · Wuming Wang · Gang Lu · Wai-Yee Chan · Hui Zhao · Chenli Liu · Xingguo Liu

18 March 2026 at 08:00

A mitochondrial transplantation approach rescues mitochondrial deficiency and prevents mitochondrial DNA depletion syndrome, Leigh syndrome, and Parkinson’s disease in cellular and mouse models.

3DCity-LLM: Empowering Multi-modality Large Language Models for 3D City-scale Perception and Understanding

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

By: Yiping Chen · Jinpeng Li · Wenyu Ke · Yang Luo · Jie Ouyang · Zhongjie He · Li Liu · Hongchao Fan · Hao Wu

25 March 2026 at 12:00

arXiv:2603.23447v1 Announce Type: cross Abstract: While multi-modality large language models excel in object-centric or indoor scenarios, scaling them to 3D city-scale environments remains a formidable challenge. To bridge this gap, we propose 3DCity-LLM, a unified framework designed for 3D city-scale vision-language perception and understanding. 3DCity-LLM employs a coarse-to-fine feature encoding strategy comprising three parallel branches for target object, inter-object relationship, and global scene. To facilitate large-scale training, we introduce 3DCity-LLM-1.2M dataset that comprises approximately 1.2 million high-quality samples across seven representative task categories, ranging from fine-grained object analysis to multi-faceted scene planning. This strictly quality-controlled dataset integrates explicit 3D numerical information and diverse user-oriented simulations, enriching the question-answering diversity and realism of urban scenarios. Furthermore, we apply a multi-dimensional protocol based on text-similarity metrics and LLM-based semantic assessment to ensure faithful and comprehensive evaluations for all methods. Extensive experiments on two benchmarks demonstrate that 3DCity-LLM significantly outperforms existing state-of-the-art methods, offering a promising and meaningful direction for advancing spatial reasoning and urban intelligence. The source code and dataset are available at https://github.com/SYSU-3DSTAILab/3D-City-LLM.

Multiscale Structure-Guided Latent Diffusion for Multimodal MRI Translation

16 March 2026 at 12:00

arXiv:2603.12581v1 Announce Type: cross Abstract: Although diffusion models have achieved remarkable progress in multi-modal magnetic resonance imaging (MRI) translation tasks, existing methods still tend to suffer from anatomical inconsistencies or degraded texture details when handling arbitrary missing-modality scenarios. To address these issues, we propose a latent diffusion-based multi-modal MRI translation framework, termed MSG-LDM. By leveraging the available modalities, the proposed method infers complete structural information, which preserves reliable boundary details. Specifically, we introduce a style--structure disentanglement mechanism in the latent space, which explicitly separates modality-specific style features from shared structural representations, and jointly models low-frequency anatomical layouts and high-frequency boundary details in a multi-scale feature space. During the structure disentanglement stage, high-frequency structural information is explicitly incorporated to enhance feature representations, guiding the model to focus on fine-grained structural cues while learning modality-invariant low-frequency anatomical representations. Furthermore, to reduce interference from modality-specific styles and improve the stability of structure representations, we design a style consistency loss and a structure-aware loss. Extensive experiments on the BraTS2020 and WMH datasets demonstrate that the proposed method outperforms existing MRI synthesis approaches, particularly in reconstructing complete structures. The source code is publicly available at https://github.com/ziyi-start/MSG-LDM.

CRTAM inhibition mitigates toxicity of immune checkpoint inhibitors without antitumor efficacy trade-off

Nature Cancer

By: Si-Cong Ma · Zi-Xuan Rong · Zi-Peng Xu · Yan-Pei Zhang · Kui-Mao Zhuang · Hao Sun · Chuan-Hui Cao · Ze-Nan Wu · Hai-Peng Zhang · Qiang Zuo · Jia-Run Lin · Jia-Xin Cheng · Hua-Ting Qu · Duan-Duan Han · Wei Wei · Ke Liu · Xiao-Ting Cai · Ze-Qin Guo · Xue Bai · Li Liu · De-Hua Wu · Zhong-Yi Dong

5 March 2026 at 08:00

Nature Cancer, Published online: 05 March 2026; doi:10.1038/s43018-026-01135-0

Dong and colleagues report that blockade of T cell-expressed cytotoxic and regulatory T cell molecule results in selective mitigation of immune-related toxicities without affecting antitumor efficacy of immune checkpoint inhibitors.

Emergent human-like working memory from artificial neurons with intrinsic plasticity

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

By: Jingli Liu · Huannan Zheng · Bohao Zou · Kezhou Yang

17 February 2026 at 13:00

arXiv:2512.15829v2 Announce Type: replace-cross Abstract: Working memory enables the brain to integrate transient information for rapid decision-making. Artificial networks typically replicate this via recurrent or parallel architectures, yet incur high energy costs and noise sensitivity. Here we report IPNet, a hardware-software co-designed neuromorphic architecture realizing human-like working memory via neuronal intrinsic plasticity. Exploiting Joule-heating dynamics of Magnetic Tunnel Junctions (MTJs), IPNet physically emulates biological memory volatility. The memory behavior of the proposed architecture shows similar trends in n-back, free recall and memory interference tasks to that of reported human subjects. Implemented exclusively with MTJ neurons, the architecture with human-like working memory achieves 99.65% accuracy on 11-class DVS gesture datasets and maintains 99.48% on a novel 22-class time-reversed benchmark, outperforming RNN, LSTM, and 2+1D CNN baselines sharing identical backbones. For autonomous driving (DDD-20), IPNet reduces steering prediction error by 14.4% compared to ResNet-LSTM. Architecturally, we identify a 'Memory-at-the-Frontier' effect where performance is maximized at the sensing interface, validating a bio-plausible near-sensor processing paradigm. Crucially, all results rely on raw parameters from fabricated devices without optimization. Hardware-in-the-loop validation confirms the system's physical realizability. Separately, energy analysis reveals a reduction in memory power of 2,874x compared to LSTMs and 90,920x versus parallel 3D-CNNs. This capacitor-free design enables a compact ~1.5um2 footprint (28 nm CMOS): a >20-fold reduction over standard LIF neurons. Ultimately, we demonstrate that instantiating human-like working memory via intrinsic neuronal plasticity endows neural networks with the dual biological advantages of superior dynamic vision processing and minimal metabolic cost.

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