Nature Biomedical Engineering最新文献_第8页

Robust genome and cell engineering via in vitro and in situ circularized RNAs. 通过体外和原位环化 RNA 实现强大的基因组和细胞工程。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-26 DOI: 10.1038/s41551-024-01245-z

Michael Tong, Nathan Palmer, Amir Dailamy, Aditya Kumar, Hammza Khaliq, Sangwoo Han, Emma Finburgh, Madeleine Wing, Camilla Hong, Yichen Xiang, Katelyn Miyasaki, Andrew Portell, Joseph Rainaldi, Amanda Suhardjo, Sami Nourreddine, Wei Leong Chew, Ester J Kwon, Prashant Mali

{"title":"Robust genome and cell engineering via in vitro and in situ circularized RNAs.","authors":"Michael Tong, Nathan Palmer, Amir Dailamy, Aditya Kumar, Hammza Khaliq, Sangwoo Han, Emma Finburgh, Madeleine Wing, Camilla Hong, Yichen Xiang, Katelyn Miyasaki, Andrew Portell, Joseph Rainaldi, Amanda Suhardjo, Sami Nourreddine, Wei Leong Chew, Ester J Kwon, Prashant Mali","doi":"10.1038/s41551-024-01245-z","DOIUrl":"10.1038/s41551-024-01245-z","url":null,"abstract":"Circularization can improve RNA persistence, yet simple and scalable approaches to achieve this are lacking. Here we report two methods that facilitate the pursuit of circular RNAs (cRNAs): cRNAs developed via in vitro circularization using group II introns, and cRNAs developed via in-cell circularization by the ubiquitously expressed RtcB protein. We also report simple purification protocols that enable high cRNA yields (40-75%) while maintaining low immune responses. These methods and protocols facilitate a broad range of applications in stem cell engineering as well as robust genome and epigenome targeting via zinc finger proteins and CRISPR-Cas9. Notably, cRNAs bearing the encephalomyocarditis internal ribosome entry enabled robust expression and persistence compared with linear capped RNAs in cardiomyocytes and neurons, which highlights the utility of cRNAs in these non-dividing cells. We also describe genome targeting via deimmunized Cas9 delivered as cRNA and a long-range multiplexed protein engineering methodology for the combinatorial screening of deimmunized protein variants that enables compatibility between persistence of expression and immunogenicity in cRNA-delivered proteins. The cRNA toolset will aid research and the development of therapeutics.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":26.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073377","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

Standardizing designed and emergent quantitative features in microphysiological systems 将微观生理系统中设计和出现的定量特征标准化。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-26 DOI: 10.1038/s41551-024-01236-0

Dennis M. Nahon, Renée Moerkens, Hande Aydogmus, Bas Lendemeijer, Adriana Martínez-Silgado, Jeroen M. Stein, Milica Dostanić, Jean-Philippe Frimat, Cristina Gontan, Mees N. S. de Graaf, Michel Hu, Dhanesh G. Kasi, Lena S. Koch, Kieu T. T. Le, Sangho Lim, Heleen H. T. Middelkamp, Joram Mooiweer, Paul Motreuil-Ragot, Eva Niggl, Cayetano Pleguezuelos-Manzano, Jens Puschhof, Nele Revyn, José M. Rivera-Arbelaez, Jelle Slager, Laura M. Windt, Mariia Zakharova, Berend J. van Meer, Valeria V. Orlova, Femke M. S. de Vrij, Sebo Withoff, Massimo Mastrangeli, Andries D. van der Meer, Christine L. Mummery

{"title":"Standardizing designed and emergent quantitative features in microphysiological systems","authors":"Dennis M. Nahon, Renée Moerkens, Hande Aydogmus, Bas Lendemeijer, Adriana Martínez-Silgado, Jeroen M. Stein, Milica Dostanić, Jean-Philippe Frimat, Cristina Gontan, Mees N. S. de Graaf, Michel Hu, Dhanesh G. Kasi, Lena S. Koch, Kieu T. T. Le, Sangho Lim, Heleen H. T. Middelkamp, Joram Mooiweer, Paul Motreuil-Ragot, Eva Niggl, Cayetano Pleguezuelos-Manzano, Jens Puschhof, Nele Revyn, José M. Rivera-Arbelaez, Jelle Slager, Laura M. Windt, Mariia Zakharova, Berend J. van Meer, Valeria V. Orlova, Femke M. S. de Vrij, Sebo Withoff, Massimo Mastrangeli, Andries D. van der Meer, Christine L. Mummery","doi":"10.1038/s41551-024-01236-0","DOIUrl":"10.1038/s41551-024-01236-0","url":null,"abstract":"Microphysiological systems (MPSs) are cellular models that replicate aspects of organ and tissue functions in vitro. In contrast with conventional cell cultures, MPSs often provide physiological mechanical cues to cells, include fluid flow and can be interlinked (hence, they are often referred to as microfluidic tissue chips or organs-on-chips). Here, by means of examples of MPSs of the vascular system, intestine, brain and heart, we advocate for the development of standards that allow for comparisons of quantitative physiological features in MPSs and humans. Such standards should ensure that the in vivo relevance and predictive value of MPSs can be properly assessed as fit-for-purpose in specific applications, such as the assessment of drug toxicity, the identification of therapeutics or the understanding of human physiology or disease. Specifically, we distinguish designed features, which can be controlled via the design of the MPS, from emergent features, which describe cellular function, and propose methods for improving MPSs with readouts and sensors for the quantitative monitoring of complex physiology towards enabling wider end-user adoption and regulatory acceptance. This Perspective discusses the need for standards that allow for comparisons of quantitative physiological features in microphysiological systems and humans.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 8","pages":"941-962"},"PeriodicalIF":26.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073378","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 vision-language foundation model for the generation of realistic chest X-ray images. 用于生成逼真胸部 X 光图像的视觉语言基础模型。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-26 DOI: 10.1038/s41551-024-01246-y

Christian Bluethgen, Pierre Chambon, Jean-Benoit Delbrouck, Rogier van der Sluijs, Małgorzata Połacin, Juan Manuel Zambrano Chaves, Tanishq Mathew Abraham, Shivanshu Purohit, Curtis P Langlotz, Akshay S Chaudhari

{"title":"A vision-language foundation model for the generation of realistic chest X-ray images.","authors":"Christian Bluethgen, Pierre Chambon, Jean-Benoit Delbrouck, Rogier van der Sluijs, Małgorzata Połacin, Juan Manuel Zambrano Chaves, Tanishq Mathew Abraham, Shivanshu Purohit, Curtis P Langlotz, Akshay S Chaudhari","doi":"10.1038/s41551-024-01246-y","DOIUrl":"10.1038/s41551-024-01246-y","url":null,"abstract":"The paucity of high-quality medical imaging datasets could be mitigated by machine learning models that generate compositionally diverse images that faithfully represent medical concepts and pathologies. However, large vision-language models are trained on natural images, and the diversity distribution of the generated images substantially differs from that of medical images. Moreover, medical language involves specific and semantically rich vocabulary. Here we describe a domain-adaptation strategy for large vision-language models that overcomes distributional shifts. Specifically, by leveraging publicly available datasets of chest X-ray images and the corresponding radiology reports, we adapted a latent diffusion model pre-trained on pairs of natural images and text descriptors to generate diverse and visually plausible synthetic chest X-ray images (as confirmed by board-certified radiologists) whose appearance can be controlled with free-form medical text prompts. The domain-adaptation strategy for the text-conditioned synthesis of medical images can be used to augment training datasets and is a viable alternative to the sharing of real medical images for model training and fine-tuning.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":" ","pages":""},"PeriodicalIF":26.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073376","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

The formation and maintenance of peri-implant fibrosis requires skeletal cells expressing the leptin receptor 种植体周围纤维化的形成和维持需要表达瘦素受体的骨骼细胞

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-14 DOI: 10.1038/s41551-024-01244-0

引用次数: 0

A base editor for the long-term restoration of auditory function in mice with recessive profound deafness 隐性极重度耳聋小鼠听觉功能长期恢复的基础编辑器

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-12 DOI: 10.1038/s41551-024-01235-1

Chong Cui, Shengyi Wang, Daqi Wang, Jingjing Zhao, Bowei Huang, Biyun Zhu, Yuxin Chen, Honghai Tang, Yu Han, Cheng Ye, Dan Mu, Chengdong Zhang, Yuan Yang, Yihan Bao, Jun Lv, Shuang Han, Geng-Lin Li, Huawei Li, Yilai Shu

{"title":"A base editor for the long-term restoration of auditory function in mice with recessive profound deafness","authors":"Chong Cui, Shengyi Wang, Daqi Wang, Jingjing Zhao, Bowei Huang, Biyun Zhu, Yuxin Chen, Honghai Tang, Yu Han, Cheng Ye, Dan Mu, Chengdong Zhang, Yuan Yang, Yihan Bao, Jun Lv, Shuang Han, Geng-Lin Li, Huawei Li, Yilai Shu","doi":"10.1038/s41551-024-01235-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01235-1","url":null,"abstract":"A prevalent recessive mutation (c.2485C>T, p.Q829X) within the OTOF gene leads to profound prelingual hearing loss. Here we show that in Otof mice harbouring a mutation (c.2482C>T, p.Q828X) homozygous to human OTOF that faithfully mimics the hearing-loss phenotype, a base editor (consisting of the deaminase ABE7.10max and the Cas9 variant SpCas9-NG) packaged in adeno-associated viruses and injected into the inner ear of the mice via the round-window membrane effectively corrected the pathogenic mutation, with no apparent off-target effects. The treatment restored the levels of the otoferlin protein in 88% of the inner hair cells and stably rescued the auditory function of the mice to near-wild-type levels for over 1.5 years while improving synaptic exocytosis in the inner hair cells. We also show that an adenine base editor that targets the prevalent human OTOF mutation restored hearing in humanized mice to levels comparable to those of the wild-type counterparts. Base editors may be effective for the treatment of hereditary deafness.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918827","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 base editor for correcting deafness 用于矫正耳聋的基础编辑器

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-12 DOI: 10.1038/s41551-024-01234-2

Bence György

引用次数: 0

Contributions of network structure, chemoarchitecture and diagnostic categories to transitions between cognitive topographies 网络结构、化学体系结构和诊断类别对认知地形之间转换的贡献。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-05 DOI: 10.1038/s41551-024-01242-2

Andrea I. Luppi, S. Parker Singleton, Justine Y. Hansen, Keith W. Jamison, Danilo Bzdok, Amy Kuceyeski, Richard F. Betzel, Bratislav Misic

{"title":"Contributions of network structure, chemoarchitecture and diagnostic categories to transitions between cognitive topographies","authors":"Andrea I. Luppi, S. Parker Singleton, Justine Y. Hansen, Keith W. Jamison, Danilo Bzdok, Amy Kuceyeski, Richard F. Betzel, Bratislav Misic","doi":"10.1038/s41551-024-01242-2","DOIUrl":"10.1038/s41551-024-01242-2","url":null,"abstract":"The mechanisms linking the brain’s network structure to cognitively relevant activation patterns remain largely unknown. Here, by leveraging principles of network control, we show how the architecture of the human connectome shapes transitions between 123 experimentally defined cognitive activation maps (cognitive topographies) from the NeuroSynth meta-analytic database. Specifically, we systematically integrated large-scale multimodal neuroimaging data from functional magnetic resonance imaging, diffusion tractography, cortical morphometry and positron emission tomography to simulate how anatomically guided transitions between cognitive states can be reshaped by neurotransmitter engagement or by changes in cortical thickness. Our model incorporates neurotransmitter-receptor density maps (18 receptors and transporters) and maps of cortical thickness pertaining to a wide range of mental health, neurodegenerative, psychiatric and neurodevelopmental diagnostic categories (17,000 patients and 22,000 controls). The results provide a comprehensive look-up table charting how brain network organization and chemoarchitecture interact to manifest different cognitive topographies, and establish a principled foundation for the systematic identification of ways to promote selective transitions between cognitive topographies. An analysis of neuroimaging data across mental health, neurodegenerative, psychiatric and neurodevelopmental diagnostic categories highlights how brain network organization and chemoarchitecture interact to shape cognitive topographies.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 9","pages":"1142-1161"},"PeriodicalIF":26.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41551-024-01242-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PEGylated bacteria penetrate mucus and strengthen the gut mucosal barrier 聚乙二醇化细菌可穿透粘液，增强肠道粘膜屏障。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-08-01 DOI: 10.1038/s41551-024-01231-5

引用次数: 0

Deep mutational scanning and machine learning for the analysis of antimicrobial-peptide features driving membrane selectivity 利用深度突变扫描和机器学习分析驱动膜选择性的抗菌肽特征

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-07-31 DOI: 10.1038/s41551-024-01243-1

Justin R. Randall, Luiz C. Vieira, Claus O. Wilke, Bryan W. Davies

{"title":"Deep mutational scanning and machine learning for the analysis of antimicrobial-peptide features driving membrane selectivity","authors":"Justin R. Randall, Luiz C. Vieira, Claus O. Wilke, Bryan W. Davies","doi":"10.1038/s41551-024-01243-1","DOIUrl":"10.1038/s41551-024-01243-1","url":null,"abstract":"Many antimicrobial peptides directly disrupt bacterial membranes yet can also damage mammalian membranes. It is therefore central to their therapeutic use that rules governing the membrane selectivity of antimicrobial peptides be deciphered. However, this is difficult even for short peptides owing to the large combinatorial space of amino acid sequences. Here we describe a method for measuring the loss or maintenance of antimicrobial-peptide activity for thousands of peptide-sequence variants simultaneously, and its application to Protegrin-1, a potent yet toxic antimicrobial peptide, to determine the positional importance and flexibility of residues across its sequence while identifying variants with changes in membrane selectivity. More bacterially selective variants maintained a membrane-bound secondary structure while avoiding aromatic residues and cysteine pairs. A machine-learning model trained with our datasets accurately predicted membrane-specific activities for over 5.7 million Protegrin-1 variants, and identified one variant that showed substantially reduced toxicity and retention of activity in a mouse model of intraperitoneal infection. The high-throughput methodology may help elucidate sequence–structure–function relationships in antimicrobial peptides and inform the design of peptide-based synthetic drugs. A high-throughput mutation-scanning method for interrogating sequence variation in antimicrobial peptides facilitates the understanding of sequence–structure–function relationships affecting the membrane selectivity of antimicrobial peptides.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 7","pages":"842-853"},"PeriodicalIF":26.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857857","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

Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor 通过对表达瘦素受体的骨骼细胞进行功能抑制，预防和治疗种植体周围纤维化

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-07-31 DOI: 10.1038/s41551-024-01238-y

Vincentius Jeremy Suhardi, Anastasia Oktarina, Mohammed Hammad, Yingzhen Niu, Qingdian Li, Andrew Thomson, Juan Lopez, Jason McCormick, Ugur M. Ayturk, Matthew B. Greenblatt, Lionel B. Ivashkiv, Mathias P. G. Bostrom, Xu Yang

{"title":"Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor","authors":"Vincentius Jeremy Suhardi, Anastasia Oktarina, Mohammed Hammad, Yingzhen Niu, Qingdian Li, Andrew Thomson, Juan Lopez, Jason McCormick, Ugur M. Ayturk, Matthew B. Greenblatt, Lionel B. Ivashkiv, Mathias P. G. Bostrom, Xu Yang","doi":"10.1038/s41551-024-01238-y","DOIUrl":"10.1038/s41551-024-01238-y","url":null,"abstract":"The cellular and molecular mediators of peri-implant fibrosis—a most common reason for implant failure and for surgical revision after the replacement of a prosthetic joint—remain unclear. Here we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of skeletal cells expressing the leptin receptor (LEPR) and that these cells are necessary and sufficient to generate and maintain peri-implant fibrotic tissue. In a mouse model of tibial implantation and osseointegration that mimics partial knee arthroplasty, genetic ablation of LEPR+ cells prevented peri-implant fibrosis and the implantation of LEPR+ cells from peri-implant fibrotic tissue was sufficient to induce fibrosis in secondary hosts. Conditional deletion of the adhesion G-protein-coupled receptor F5 (ADGRF5) in LEPR+ cells attenuated peri-implant fibrosis while augmenting peri-implant bone formation, and ADGRF5 inhibition by the intra-articular or systemic administration of neutralizing anti-ADGRF5 in the mice prevented and reversed peri-implant fibrosis. Pharmaceutical agents that inhibit the ADGRF5 pathway in LEPR+ cells may be used to prevent and treat peri-implant fibrosis. The generation and maintenance of peri-implant fibrotic tissue requires skeletal cells expressing the leptin receptor and can be prevented and reversed via the functional inhibition of these cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 10","pages":"1285-1307"},"PeriodicalIF":26.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857858","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