Changjoon Keum, Haejin Yeom, Tae Il Noh, Seung Yong Yi, Soyeong Jin, Chaekyu Kim, Ji Sung Shim, Sung Goo Yoon, Hojun Kim, Kwan Hyi Lee, Seok Ho Kang, Youngdo Jeong
{"title":"Diagnosis of early-stage bladder cancer via unprocessed urine samples at the point of care","authors":"Changjoon Keum, Haejin Yeom, Tae Il Noh, Seung Yong Yi, Soyeong Jin, Chaekyu Kim, Ji Sung Shim, Sung Goo Yoon, Hojun Kim, Kwan Hyi Lee, Seok Ho Kang, Youngdo Jeong","doi":"10.1038/s41551-024-01298-0","DOIUrl":"https://doi.org/10.1038/s41551-024-01298-0","url":null,"abstract":"<p>Diagnostic kits for the optical detection of bladder cancer in urine can facilitate effective screening and surveillance. However, the heterogeneity of urine samples, owing to patients with bladder cancer often presenting with haematuria, interfere with the transduction of the optical signal. Here we describe the development and point-of-care performance of a device for the detection of bladder cancer that obviates the need for sample processing. The device leverages the enzymatic release of organogel particles carrying solvatochromic fluorophores in the presence of urinary hyaluronidases—a bladder cancer biomarker. Owing to buoyancy, the particles transfer from the urine sample into the organic phase, where the change in fluorescence can be measured via a smartphone without interference from blood proteins. In a double-blind study with 80 unprocessed urine samples from patients with bladder cancer (including samples with haematuria) or other genitourinary diseases and with 25 samples from healthy participants, our system distinguished the cancerous samples, including those with early-stage bladder cancer, with accuracies of about 90%. Obviating the need for sample pretreatment may facilitate the at-home detection of bladder cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735592","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}
Xuexiang Han, Mohamad-Gabriel Alameh, Ying Xu, Rohan Palanki, Rakan El-Mayta, Garima Dwivedi, Kelsey L. Swingle, Junchao Xu, Ningqiang Gong, Lulu Xue, Qiangqiang Shi, Il-Chul Yoon, Claude C. Warzecha, James M. Wilson, Drew Weissman, Michael J. Mitchell
{"title":"Optimization of the activity and biodegradability of ionizable lipids for mRNA delivery via directed chemical evolution","authors":"Xuexiang Han, Mohamad-Gabriel Alameh, Ying Xu, Rohan Palanki, Rakan El-Mayta, Garima Dwivedi, Kelsey L. Swingle, Junchao Xu, Ningqiang Gong, Lulu Xue, Qiangqiang Shi, Il-Chul Yoon, Claude C. Warzecha, James M. Wilson, Drew Weissman, Michael J. Mitchell","doi":"10.1038/s41551-024-01267-7","DOIUrl":"10.1038/s41551-024-01267-7","url":null,"abstract":"Ionizable lipids largely determine the biocompatibility of lipid nanoparticles (LNPs) and the efficacy for mRNA delivery. Rational design and combinatorial synthesis have led to the development of potent and biodegradable ionizable lipids, yet methodologies for the stepwise optimization of ionizable lipid structure are lacking. Here we show that iterative chemical derivatization and combinatorial chemistry, and in particular the amine–aldehyde–alkyne coupling reaction, can be leveraged to iteratively accelerate the structural optimization of propargylamine-based ionizable lipids (named A3-lipids) to improve their delivery activity and biodegradability. Through five cycles of such directed chemical evolution, we identified dozens of biodegradable and asymmetric A3-lipids with delivery activity comparable to or better than a benchmark ionizable lipid. We then derived structure−activity relationships for the headgroup, ester linkage and tail. Compared with standard ionizable lipids, the lead A3-lipid improved the hepatic delivery of an mRNA-based genome editor and the intramuscular delivery of an mRNA vaccine against SARS-CoV-2. Structural criteria for ionizable lipids discovered via directed chemical evolution may accelerate the development of LNPs for mRNA delivery. Directed chemical evolution can iteratively accelerate the structural optimization of ionizable lipids to improve their delivery activity and biodegradability for applications in lipid nanoparticle-mediated mRNA delivery.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1412-1424"},"PeriodicalIF":26.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684272","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}
{"title":"Offbeat drug-delivery tactics","authors":"","doi":"10.1038/s41551-024-01317-0","DOIUrl":"10.1038/s41551-024-01317-0","url":null,"abstract":"More off-the-beaten-track strategies are needed for enhancing the accumulation of drugs at target sites, for improving the drugs’ cell-type specificity and for reducing their off-target toxicity.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1323-1324"},"PeriodicalIF":26.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41551-024-01317-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690831","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}
{"title":"Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels","authors":"Yuxia Liu, Yuanyuan He, Jiahuan Tong, Shengyang Guo, Xinyu Zhang, Zichao Luo, Linlin Sun, Chao Chang, Bilin Zhuang, Xiaogang Liu","doi":"10.1038/s41551-024-01288-2","DOIUrl":"https://doi.org/10.1038/s41551-024-01288-2","url":null,"abstract":"<p>Activation of the ion channel transient receptor potential vanilloid 1 (TRPV1), which is integral to pain perception, leads to an expansion of channel width, facilitating the passage of cations and large organic molecules. However, the permeability of TRPV1 channels to water remains uncertain, owing to a lack of suitable tools to study water dynamics. Here, using upconversion nanophosphors to discriminate between H<sub>2</sub>O and D<sub>2</sub>O, by monitoring water permeability across activated TRPV1 at the single-cell and single-molecule levels, and by combining single-channel current measurements with molecular dynamics simulations, we show that water molecules flow through TRPV1 and reveal a direct connection between water migration, cation flow and TRPV1 functionality. We also show in mouse models of acute or chronic inflammatory pain that the administration of deuterated water suppresses TRPV1 activity, interrupts the transmission of pain signals and mitigates pain without impacting other neurological responses. Solvent-mediated analgesia may inspire alternative options for pain management.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"11 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678280","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}
Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu
{"title":"Clinical validation of a wearable ultrasound sensor of blood pressure","authors":"Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu","doi":"10.1038/s41551-024-01279-3","DOIUrl":"https://doi.org/10.1038/s41551-024-01279-3","url":null,"abstract":"<p>Options for the continuous and non-invasive monitoring of blood pressure are limited. Cuff-based sphygmomanometers are widely available, yet provide only discrete measurements. The clinical gold-standard approach for the continuous monitoring of blood pressure requires an arterial line, which is too invasive for routine use. Wearable ultrasound for the continuous and non-invasive monitoring of blood pressure promises to elevate the quality of patient care, yet the isolated sonographic windows in the most advanced prototypes can lead to inaccurate or error-prone measurements, and the safety and performance of these devices have not been thoroughly evaluated. Here we describe validation studies, conducted during daily activities at home, in the outpatient clinic, in the cardiac catheterization laboratory and in the intensive care unit, of the safety and performance of a wearable ultrasound sensor for blood pressure monitoring. The sensor has closely connected sonographic windows and a backing layer that improves the sensor’s accuracy and reliability to meet the highest requirements of clinical standards. The validation results support the clinical use of the sensor.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"62 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673167","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}
{"title":"Endocytic tagging for degradation","authors":"Filipe V. Almeida","doi":"10.1038/s41551-024-01293-5","DOIUrl":"10.1038/s41551-024-01293-5","url":null,"abstract":"Proteins that tag surface receptors for degradation by triggering their endocytosis can be computationally designed so that they do not compete with native receptor ligands for binding.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1328-1328"},"PeriodicalIF":26.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670682","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}
Silvia Menegatti, Sheila Lopez-Cobo, Aurelien Sutra Del Galy, Jaime Fuentealba, Lisseth Silva, Laetitia Perrin, Sandrine Heurtebise-Chrétien, Valentine Pottez-Jouatte, Aurelie Darbois, Nina Burgdorf, Anne-Laure Privat, Albane Simon, Marguerite Laprie-Sentenac, Michael Saitakis, Bryce Wick, Beau R. Webber, Branden S. Moriarity, Olivier Lantz, Sebastian Amigorena, Laurie Menger
{"title":"Ablation of FAS confers allogeneic CD3– CAR T cells with resistance to rejection by T cells and natural killer cells","authors":"Silvia Menegatti, Sheila Lopez-Cobo, Aurelien Sutra Del Galy, Jaime Fuentealba, Lisseth Silva, Laetitia Perrin, Sandrine Heurtebise-Chrétien, Valentine Pottez-Jouatte, Aurelie Darbois, Nina Burgdorf, Anne-Laure Privat, Albane Simon, Marguerite Laprie-Sentenac, Michael Saitakis, Bryce Wick, Beau R. Webber, Branden S. Moriarity, Olivier Lantz, Sebastian Amigorena, Laurie Menger","doi":"10.1038/s41551-024-01282-8","DOIUrl":"https://doi.org/10.1038/s41551-024-01282-8","url":null,"abstract":"<p>Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host’s immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of <i>Fas</i> or <i>B2m</i> in allo- T cells increases their survival in immunocompetent mice. Human <i>B2M</i><sup>–</sup> allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas <i>FAS</i><sup>–</sup> CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. <i>CD3</i><sup>–</sup> <i>FAS</i><sup>–</sup> CAR T cells outperformed <i>CD3</i><sup>–</sup> <i>B2M</i><sup><i>–</i></sup> CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of <i>CD3</i><sup>–</sup> <i>FAS</i><sup>–</sup> allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"32 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665501","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}
{"title":"Stress impacts immunity via the gut","authors":"Jennifer Haskell","doi":"10.1038/s41551-024-01294-4","DOIUrl":"10.1038/s41551-024-01294-4","url":null,"abstract":"Stress-sensitive neural circuitry affects immunity via the gut microbiome.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1327-1327"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637042","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}
{"title":"Dyeing mice transparent","authors":"Alessandra Griffo","doi":"10.1038/s41551-024-01292-6","DOIUrl":"10.1038/s41551-024-01292-6","url":null,"abstract":"A water-soluble dye that absorbs blue light strongly makes it easier to turn mice transparent.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1326-1326"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637055","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}
{"title":"Seeing ageing through retinal images","authors":"Pep Pàmies","doi":"10.1038/s41551-024-01291-7","DOIUrl":"10.1038/s41551-024-01291-7","url":null,"abstract":"A biomarker in retinal images identified by a deep-learning algorithm can predict biological age as well as mortality and morbidity.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 11","pages":"1325-1325"},"PeriodicalIF":26.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637033","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}