Nature Biomedical Engineering最新文献

英文中文

Anchored random reverse primer sequencing for quantitative detection of novel gene fusions. 锚定随机反向引物测序用于定量检测新的基因融合。

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2026-01-02 DOI: 10.1038/s41551-025-01564-9

Xuehao Xiu, Yi Wu, Jiangxue Li, Dongfa Lin, Xiao Sun, Xinglei Su, Zhi Weng, Xiaolei Zuo, Xiurong Yang, Chunhai Fan, Yudong Wang, David Yu Zhang, Ping Song

Identifying novel gene fusions is critical for cancer diagnosis and drug development. While a few advanced methods have shown the capability to detect gene fusions involving unknown partners, comprehensive detection of gene fusions, especially of those with low copy numbers, remains a challenge. Indeed, most current panel-based sequencing methods fall short in reliability and cost efficiency. Here we present a method for detecting potentially novel gene fusions using anchored random reverse primers (ARRP) during PCR-based library construction, allowing the simultaneous capture of mutations and RNA splicing variants. Furthermore, the combination with blocker displacement amplification technology enables a median of 22-fold allele enrichment for gene fusions, achieving a limit of detection ~10-fold lower than that of current technologies and resulting in an 8-fold cost reduction. Using ARRP-seq, we identify numerous novel fusions in 98 clinical tissue samples, showcasing its diagnostic potential in prostate cancer and capacity for personalized diagnostics in cervical cancer.

鉴定新的基因融合体对癌症诊断和药物开发至关重要。虽然一些先进的方法已经显示出检测涉及未知伴侣的基因融合的能力，但全面检测基因融合，特别是那些拷贝数低的基因融合，仍然是一个挑战。事实上，目前大多数基于面板的测序方法在可靠性和成本效率方面都存在不足。在这里，我们提出了一种在基于pcr的文库构建过程中使用锚定随机反向引物（ARRP）检测潜在新基因融合的方法，允许同时捕获突变和RNA剪接变异体。此外，与阻断剂置换扩增技术的结合使基因融合的等位基因富集中位数为22倍，检测限比现有技术低10倍，成本降低8倍。使用ARRP-seq，我们在98个临床组织样本中发现了许多新的融合物，展示了其在前列腺癌和宫颈癌个性化诊断中的潜力。

{"title":"Anchored random reverse primer sequencing for quantitative detection of novel gene fusions.","authors":"Xuehao Xiu, Yi Wu, Jiangxue Li, Dongfa Lin, Xiao Sun, Xinglei Su, Zhi Weng, Xiaolei Zuo, Xiurong Yang, Chunhai Fan, Yudong Wang, David Yu Zhang, Ping Song","doi":"10.1038/s41551-025-01564-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01564-9","url":null,"abstract":"<p><p>Identifying novel gene fusions is critical for cancer diagnosis and drug development. While a few advanced methods have shown the capability to detect gene fusions involving unknown partners, comprehensive detection of gene fusions, especially of those with low copy numbers, remains a challenge. Indeed, most current panel-based sequencing methods fall short in reliability and cost efficiency. Here we present a method for detecting potentially novel gene fusions using anchored random reverse primers (ARRP) during PCR-based library construction, allowing the simultaneous capture of mutations and RNA splicing variants. Furthermore, the combination with blocker displacement amplification technology enables a median of 22-fold allele enrichment for gene fusions, achieving a limit of detection ~10-fold lower than that of current technologies and resulting in an 8-fold cost reduction. Using ARRP-seq, we identify numerous novel fusions in 98 clinical tissue samples, showcasing its diagnostic potential in prostate cancer and capacity for personalized diagnostics in cervical cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":26.8,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Zwitterionic lipid design enhances mRNA cancer vaccine efficacy and reduces reactogenicity. 两性离子脂质设计提高mRNA癌症疫苗的效力并降低反应原性。

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2026-01-02 DOI: 10.1038/s41551-025-01580-9

引用次数: 0

Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids 具有破坏膜稳定性的两性离子脂质的mRNA-LNPs具有低反应性和高肿瘤抗原表达

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-18 DOI: 10.1038/s41551-025-01577-4

Yu Zhao, Ruoxin Li, Pingchuan Liu, Jialiang Wang, Yanru Cui, Yufei Ma, Zeyu Cao, Meng Cui, Sijin Luozhong, Erica Wagner, Amy Laflin, Yaopeng Ding, Yuping Hu, Zhen Tian, Chenjue Tang, Simian Cai, Hamilton Young, Di Liu, Wenchao Gu, Sean Bailey, Shaoyi Jiang

引用次数: 0

2025 in review 2025年回顾

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-16 DOI: 10.1038/s41551-025-01595-2

In this editorial, we feature several standout papers across disciplines published in Nature Biomedical Engineering in 2025.

在这篇社论中，我们将介绍2025年发表在《自然生物医学工程》上的几篇跨学科的杰出论文。

引用次数: 0

A trispecific antibody engaging T cells with tumour and myeloid cells augments antitumour immunity 一种与T细胞和骨髓细胞结合的三特异性抗体增强了抗肿瘤免疫

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-10 DOI: 10.1038/s41551-025-01569-4

Changrui Yang, Shanni Guo, Kaiyan Ye, Yizong Ding, Xingzhong Zhao, Yucheng T. Yang, Bowen Sun, Shuyi Qian, Mei-Chun Cai, Luyan Liu, Libing Xiang, Xia Yin, Xing-Ming Zhao, Jieyi Wang, Jiwei Zhang, Wen Di, Guanglei Zhuang, Fan Yang

Immunologically unresponsive tumours often resist immune checkpoint inhibitors due to the low abundance of tumour-specific T cells and an immunosuppressive microenvironment, despite pronounced infiltration of non-tumour-specific (bystander) T cells. Here we analysed single-cell RNA sequencing data from 300 patients across 17 tumour types, identifying abundant but functionally restrained bystander T cells in multiple malignancies, including ovarian and colorectal cancer. To enhance antitumour immunity in such contexts, we engineered B7H3xCD3xPDL1, a trispecific immunoglobulin-based T cell engager targeting B7H3, CD3 and PDL1, to redirect T cells while mitigating immunosuppression. Functional validation in co-culture systems, patient-derived tumour suspensions and fragments, and humanized mouse models showed T cell activation and tumour killing. Imaging cytometry and single-cell transcriptomics revealed IFNγ-dependent macrophage reprogramming and IL-15 secretion, establishing a feed-forward loop that augments T cell functionality. A machine learning model trained on ex vivo cytotoxicity and transcriptomic data predicted patient responsiveness, supporting data-driven clinical stratification for solid tumour immunotherapy.

尽管存在明显的非肿瘤特异性（旁观者）T细胞浸润，但由于肿瘤特异性T细胞丰度低和免疫抑制微环境，免疫无反应的肿瘤通常会抵抗免疫检查点抑制剂。在这里，我们分析了来自17种肿瘤类型的300名患者的单细胞RNA测序数据，在包括卵巢癌和结直肠癌在内的多种恶性肿瘤中发现了丰富但功能受抑制的旁观者T细胞。为了在这种情况下增强抗肿瘤免疫，我们设计了B7H3xCD3xPDL1，一种基于三特异性免疫球蛋白的T细胞参与器，靶向B7H3、CD3和PDL1，在减轻免疫抑制的同时重定向T细胞。共培养系统、患者来源的肿瘤悬浮液和碎片以及人源化小鼠模型的功能验证显示T细胞活化和肿瘤杀伤。成像细胞术和单细胞转录组学揭示了ifn γ依赖性巨噬细胞重编程和IL-15分泌，建立了一个增强T细胞功能的前反馈回路。体外细胞毒性和转录组学数据训练的机器学习模型预测了患者的反应性，支持数据驱动的实体肿瘤免疫治疗临床分层。

{"title":"A trispecific antibody engaging T cells with tumour and myeloid cells augments antitumour immunity","authors":"Changrui Yang, Shanni Guo, Kaiyan Ye, Yizong Ding, Xingzhong Zhao, Yucheng T. Yang, Bowen Sun, Shuyi Qian, Mei-Chun Cai, Luyan Liu, Libing Xiang, Xia Yin, Xing-Ming Zhao, Jieyi Wang, Jiwei Zhang, Wen Di, Guanglei Zhuang, Fan Yang","doi":"10.1038/s41551-025-01569-4","DOIUrl":"https://doi.org/10.1038/s41551-025-01569-4","url":null,"abstract":"Immunologically unresponsive tumours often resist immune checkpoint inhibitors due to the low abundance of tumour-specific T cells and an immunosuppressive microenvironment, despite pronounced infiltration of non-tumour-specific (bystander) T cells. Here we analysed single-cell RNA sequencing data from 300 patients across 17 tumour types, identifying abundant but functionally restrained bystander T cells in multiple malignancies, including ovarian and colorectal cancer. To enhance antitumour immunity in such contexts, we engineered B7H3xCD3xPDL1, a trispecific immunoglobulin-based T cell engager targeting B7H3, CD3 and PDL1, to redirect T cells while mitigating immunosuppression. Functional validation in co-culture systems, patient-derived tumour suspensions and fragments, and humanized mouse models showed T cell activation and tumour killing. Imaging cytometry and single-cell transcriptomics revealed IFNγ-dependent macrophage reprogramming and IL-15 secretion, establishing a feed-forward loop that augments T cell functionality. A machine learning model trained on ex vivo cytotoxicity and transcriptomic data predicted patient responsiveness, supporting data-driven clinical stratification for solid tumour immunotherapy.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"144 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trispecific engager overcomes tumoural immunosuppressive environment. 三特异性接合体克服肿瘤免疫抑制环境。

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-10 DOI: 10.1038/s41551-025-01571-w

Fernando Aranda,Aline Risson,Pedro Berraondo

引用次数: 0

Publisher Correction: CRISPR-GPT for agentic automation of gene-editing experiments. 出版者更正：CRISPR-GPT用于基因编辑实验的代理自动化。

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-08 DOI: 10.1038/s41551-025-01589-0

Yuanhao Qu,Kaixuan Huang,Ming Yin,Kanghong Zhan,Dyllan Liu,Di Yin,Henry C Cousins,William A Johnson,Xiaotong Wang,Mihir Shah,Russ B Altman,Denny Zhou,Mengdi Wang,Le Cong

引用次数: 0

Long-term unsupervised recalibration of cursor-based intracortical brain-computer interfaces using a hidden Markov model. 基于隐马尔可夫模型的皮层内脑机接口的长期无监督再校准。

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-08 DOI: 10.1038/s41551-025-01536-z

Guy H Wilson,Elias A Stein,Foram Kamdar,Donald T Avansino,Tsam Kiu Pun,Ronnie Gross,Tommy Hosman,Tyler Singer-Clark,Anastasia Kapitonava,Leigh R Hochberg,John D Simeral,Krishna V Shenoy,Shaul Druckmann,Jaimie M Henderson,Francis R Willett

Intracortical brain-computer interfaces (iBCIs) require frequent recalibration to maintain robust performance due to changes in neural activity that accumulate over time, which result in periods when users cannot use their device. Here we introduce a hidden Markov model to infer which targets users are moving towards during iBCI use and we retrain the system using these inferred targets, enabling unsupervised adaptation to changing neural activity. Our approach outperforms distribution alignment methods in large-scale, closed-loop simulations over two months, as well as in a closed loop with a human iBCI user over one month. Leveraging an offline dataset spanning five years of iBCI recordings, we show how target inference recalibration methods appear capable of long-term unsupervised recalibration, whereas recently proposed data-distribution-matching approaches appear to accumulate compounding errors over time. We show offline that our approach performs well on freeform datasets of a person using a home computer with an iBCI. Our results demonstrate the use of task structure to bootstrap a noisy decoder into a highly performant one, thereby overcoming one of the major barriers to clinically translating BCIs.

皮层内脑机接口（ibci）需要频繁的重新校准，以保持稳健的性能，因为随着时间的推移，神经活动的变化会累积，导致用户无法使用他们的设备。在这里，我们引入了一个隐马尔可夫模型来推断用户在使用iBCI时向哪个目标移动，我们使用这些推断的目标重新训练系统，使无监督适应不断变化的神经活动。我们的方法在两个月以上的大规模闭环模拟中优于分布对齐方法，在一个月以上的人类iBCI用户闭环模拟中也优于分布对齐方法。利用跨越五年iBCI记录的离线数据集，我们展示了目标推理重新校准方法如何能够长期无监督重新校准，而最近提出的数据分布匹配方法似乎会随着时间的推移积累复合误差。我们在线下表明，我们的方法在使用带有iBCI的家用计算机的人的自由格式数据集上表现良好。我们的研究结果证明了使用任务结构将噪声解码器引导成高性能解码器，从而克服了临床翻译bci的主要障碍之一。

{"title":"Long-term unsupervised recalibration of cursor-based intracortical brain-computer interfaces using a hidden Markov model.","authors":"Guy H Wilson,Elias A Stein,Foram Kamdar,Donald T Avansino,Tsam Kiu Pun,Ronnie Gross,Tommy Hosman,Tyler Singer-Clark,Anastasia Kapitonava,Leigh R Hochberg,John D Simeral,Krishna V Shenoy,Shaul Druckmann,Jaimie M Henderson,Francis R Willett","doi":"10.1038/s41551-025-01536-z","DOIUrl":"https://doi.org/10.1038/s41551-025-01536-z","url":null,"abstract":"Intracortical brain-computer interfaces (iBCIs) require frequent recalibration to maintain robust performance due to changes in neural activity that accumulate over time, which result in periods when users cannot use their device. Here we introduce a hidden Markov model to infer which targets users are moving towards during iBCI use and we retrain the system using these inferred targets, enabling unsupervised adaptation to changing neural activity. Our approach outperforms distribution alignment methods in large-scale, closed-loop simulations over two months, as well as in a closed loop with a human iBCI user over one month. Leveraging an offline dataset spanning five years of iBCI recordings, we show how target inference recalibration methods appear capable of long-term unsupervised recalibration, whereas recently proposed data-distribution-matching approaches appear to accumulate compounding errors over time. We show offline that our approach performs well on freeform datasets of a person using a home computer with an iBCI. Our results demonstrate the use of task structure to bootstrap a noisy decoder into a highly performant one, thereby overcoming one of the major barriers to clinically translating BCIs.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"79 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A bioorthogonal ligation system induces controlled proximity for cancer therapy. 生物正交结扎系统诱导癌症治疗的控制接近。

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-12-04 DOI: 10.1038/s41551-025-01567-6

引用次数: 0

mRNA engineering of allogeneic mesenchymal stem cells enables coordinated delivery of T cell engagers and immunotherapeutic cues 同种异体间充质干细胞的mRNA工程使T细胞接合物和免疫治疗线索的协调传递成为可能

IF 28.1 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering

Pub Date : 2025-11-28 DOI: 10.1038/s41551-025-01552-z

C. Andrew Stewart, Shaji Daniel, Elizabeth J. Curvino, Yi Zhang, Hafsa Kamboh, Kirill Sergueev, Minhtran N. Casi, Adam Chowdhury, Heng Xu, Youqiang Li, Mehmet Tosun, Matthew T. Duvernay, Yufei Shan, Mame Djigal, Maria Kireeva, Jennifer L. Biaksangi, Taylor Glassband, Fevzi Altuntas, Tuğçe Nur Yiğenoğlu, Ralph Boccia, Jesus Bardeja, Tamna Wangjam, Michael S. Singer, Murat V. Kalayoglu, Metin Kurtoglu, Albina Benson, Emily P. English, Lisa H. Tostanoski, Milos D. Miljkovic, Christopher M. Jewell

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Nature Biomedical Engineering

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀