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  • Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-19
    Susie Suh; Elliot H. Choi; Henri Leinonen; Andrzej T. Foik; Gregory A. Newby; Wei-Hsi Yeh; Zhiqian Dong; Philip D. Kiser; David C. Lyon; David R. Liu; Krzysztof Palczewski

    Cytosine base editors and adenine base editors (ABEs) can correct point mutations predictably and independent of Cas9-induced double-stranded DNA breaks (which causes substantial indel formation) and homology-directed repair (which typically leads to low editing efficiency). Here, we show, in adult mice, that a subretinal injection of an adeno-associated virus expressing an ABE and a single-guide RNA

    更新日期:2020-10-19
  • Identification of psychiatric disorder subtypes from functional connectivity patterns in resting-state electroencephalography
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-19
    Yu Zhang; Wei Wu; Russell T. Toll; Sharon Naparstek; Adi Maron-Katz; Mallissa Watts; Joseph Gordon; Jisoo Jeong; Laura Astolfi; Emmanuel Shpigel; Parker Longwell; Kamron Sarhadi; Dawlat El-Said; Yuanqing Li; Crystal Cooper; Cherise Chin-Fatt; Martijn Arns; Madeleine S. Goodkind; Madhukar H. Trivedi; Charles R. Marmar; Amit Etkin

    The understanding and treatment of psychiatric disorders, which are known to be neurobiologically and clinically heterogeneous, could benefit from the data-driven identification of disease subtypes. Here, we report the identification of two clinically relevant subtypes of post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) on the basis of robust and distinct functional connectivity

    更新日期:2020-10-19
  • Henceforth CRISPR
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-15

    In less than a decade, the genome-editing technology now recognized by the Nobel Prize in Chemistry has impacted the biological and biomedical sciences widely. What’s next for CRISPR in biomedicine?

    更新日期:2020-10-16
  • CAR-T cells targeting a nucleophosmin neoepitope exhibit potent specific activity in mouse models of acute myeloid leukaemia
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-12
    Guozhu Xie; Nikola A. Ivica; Bin Jia; Yingzhong Li; Han Dong; Yong Liang; Douglas Brown; Romee Rizwan; Jianzhu Chen

    Therapies employing chimeric antigen receptor T cells (CAR-T cells) targeting tumour-associated antigens (TAAs) can lead to on-target–off-tumour toxicity and to resistance, owing to TAA expression in normal tissues and to TAA expression loss in tumour cells. These drawbacks can be circumvented by CAR-T cells targeting tumour-specific driver gene mutations, such as the four-nucleotide duplication in

    更新日期:2020-10-12
  • A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal-vessel calibre
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-12
    Carol Y. Cheung; Dejiang Xu; Ching-Yu Cheng; Charumathi Sabanayagam; Yih-Chung Tham; Marco Yu; Tyler Hyungtaek Rim; Chew Yian Chai; Bamini Gopinath; Paul Mitchell; Richie Poulton; Terrie E. Moffitt; Avshalom Caspi; Jason C. Yam; Clement C. Tham; Jost B. Jonas; Ya Xing Wang; Su Jeong Song; Louise M. Burrell; Omar Farouque; Ling Jun Li; Gavin Tan; Daniel S. W. Ting; Wynne Hsu; Mong Li Lee; Tien Y. Wong

    Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed

    更新日期:2020-10-12
  • Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-12
    Xiaoling Xie; Yuxing Hu; Tong Ye; Yiran Chen; Lijuan Zhou; Feng Li; Xiaobo Xi; Shuang Wang; Yanjie He; Xiaoyong Gao; Wei Wei; Guanghui Ma; Yuhua Li

    Therapeutic leukaemia vaccines have shown modest potency. Here, we show that the co-encapsulation of a leukaemia-associated epitope peptide highly expressed in leukaemia patients and of the immune checkpoint inhibitor anti-programmed-cell-death-protein-1 (anti-PD-1) in degradable poly(lactic acid) microcapsules resulted in the sustained release of the peptide and of the antibody, which led to the recruitment

    更新日期:2020-10-12
  • Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-12
    Ako Ishihara; Jun Ishihara; Elyse A. Watkins; Andrew C. Tremain; Mindy Nguyen; Ani Solanki; Kiyomitsu Katsumata; Aslan Mansurov; Erica Budina; Aaron T. Alpar; Peyman Hosseinchi; Lea Maillat; Joseph W. Reda; Takahiro Kageyama; Melody A. Swartz; Eiji Yuba; Jeffrey A. Hubbell

    Interleukin-4 (IL-4) suppresses the development of multiple sclerosis in a murine model of experimental autoimmune encephalomyelitis (EAE). Here, we show that, in mice with EAE, the accumulation and persistence in the lymph nodes and spleen of a systemically administered serum albumin (SA)–IL-4 fusion protein leads to higher efficacy in preventing disease development than the administration of wild-type

    更新日期:2020-10-12
  • Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-05
    Marvin Krohn-Grimberghe; Michael J. Mitchell; Maximilian J. Schloss; Omar F. Khan; Gabriel Courties; Pedro P. G. Guimaraes; David Rohde; Sebastian Cremer; Piotr S. Kowalski; Yuan Sun; Mingchee Tan; Jamie Webster; Karin Wang; Yoshiko Iwamoto; Stephen P. Schmidt; Gregory R. Wojtkiewicz; Ribhu Nayar; Vanessa Frodermann; Maarten Hulsmans; Amanda Chung; Friedrich Felix Hoyer; Filip K. Swirski; Robert Langer;

    Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow

    更新日期:2020-10-05
  • Design and clinical implementation of an open-source bionic leg
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-10-05
    Alejandro F. Azocar; Luke M. Mooney; Jean-François Duval; Ann M. Simon; Levi J. Hargrove; Elliott J. Rouse

    In individuals with lower-limb amputations, robotic prostheses can increase walking speed, and reduce energy use, the incidence of falls and the development of secondary complications. However, safe and reliable prosthetic-limb control strategies for robust ambulation in real-world settings remain out of reach, partly because control strategies have been tested with different robotic hardware in constrained

    更新日期:2020-10-05
  • A web tool for the design of prime-editing guide RNAs
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-28
    Ryan D. Chow; Jennifer S. Chen; Johanna Shen; Sidi Chen

    Prime editing enables diverse genomic alterations to be written into target sites without requiring double-strand breaks or donor templates. The design of prime-editing guide RNAs (pegRNAs), which must be customized for each edit, can however be complex and time consuming. Compared with single guide RNAs (sgRNAs), pegRNAs have an additional 3′ extension composed of a primer binding site and a reverse-transcription

    更新日期:2020-09-28
  • AND-gate contrast agents for enhanced fluorescence-guided surgery
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-28
    John C. Widen; Martina Tholen; Joshua J. Yim; Alexander Antaris; Kerriann M. Casey; Stephan Rogalla; Alwin Klaassen; Jonathan Sorger; Matthew Bogyo

    Surgical resection of tumours requires precisely locating and defining the margins between lesions and normal tissue. However, this is made difficult by irregular margin borders. Although molecularly targeted optical contrast agents can be used to define tumour margins during surgery in real time, the selectivity of the contrast agents is often limited by the target being expressed in both healthy

    更新日期:2020-09-28
  • A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-28
    Bin Sheng Wong; Sagar R. Shah; Christopher L. Yankaskas; Vivek K. Bajpai; Pei-Hsun Wu; Deborah Chin; Brent Ifemembi; Karim ReFaey; Paula Schiapparelli; Xiaobin Zheng; Stuart S. Martin; Chen-Ming Fan; Alfredo Quiñones-Hinojosa; Konstantinos Konstantopoulos

    Clinical scores, molecular markers and cellular phenotypes have been used to predict the clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic

    更新日期:2020-09-28
  • An electric-field-responsive paramagnetic contrast agent enhances the visualization of epileptic foci in mouse models of drug-resistant epilepsy
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-28
    Cong Wang; Wanbing Sun; Jun Zhang; Jianping Zhang; Qinghua Guo; Xingyu Zhou; Dandan Fan; Haoran Liu; Ming Qi; Xihui Gao; Haiyan Xu; Zhaobing Gao; Mei Tian; Hong Zhang; Jianhong Wang; Zixuan Wei; Nicholas J. Long; Ying Mao; Cong Li

    For patients with drug-resistant focal epilepsy, excision of the epileptogenic zone is the most effective treatment approach. However, the surgery is less effective in the 15–30% of patients whose lesions are not distinct when visualized by magnetic resonance imaging (MRI). Here, we show that an intravenously administered MRI contrast agent consisting of a paramagnetic polymer coating encapsulating

    更新日期:2020-09-28
  • Extensive germline genome engineering in pigs.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-21
    Yanan Yue,Weihong Xu,Yinan Kan,Hong-Ye Zhao,Yixuan Zhou,Xiaobin Song,Jiajia Wu,Juan Xiong,Dharmendra Goswami,Meng Yang,Lydia Lamriben,Mengyuan Xu,Qi Zhang,Yu Luo,Jianxiong Guo,Shengyi Mao,Deling Jiao,Tien Dat Nguyen,Zhuo Li,Jacob V Layer,Mailin Li,Violette Paragas,Michele E Youd,Zhongquan Sun,Yuan Ding,Weilin Wang,Hongwei Dou,Lingling Song,Xueqiong Wang,Lei Le,Xin Fang,Haydy George,Ranjith Anand,Shi

    The clinical applicability of porcine xenotransplantation—a long-investigated alternative to the scarce availability of human organs for patients with organ failure—is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated

    更新日期:2020-09-21
  • Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-21
    Dzmitry Afanasenkau,Daria Kalinina,Vsevolod Lyakhovetskii,Christoph Tondera,Oleg Gorsky,Seyyed Moosavi,Natalia Pavlova,Natalia Merkulyeva,Allan V Kalueff,Ivan R Minev,Pavel Musienko

    Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand

    更新日期:2020-09-21
  • Ultrasensitive high-resolution profiling of early seroconversion in patients with COVID-19.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-18
    Maia Norman,Tal Gilboa,Alana F Ogata,Adam M Maley,Limor Cohen,Evan L Busch,Roey Lazarovits,Chih-Ping Mao,Yongfei Cai,Jun Zhang,Jared E Feldman,Blake M Hauser,Timothy M Caradonna,Bing Chen,Aaron G Schmidt,Galit Alter,Richelle C Charles,Edward T Ryan,David R Walt

    Sensitive assays are essential for the accurate identification of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report a multiplexed assay for the fluorescence-based detection of seroconversion in infected individuals from less than 1 µl of blood, and as early as the day of the first positive nucleic acid test after symptom onset. The assay uses dye-encoded

    更新日期:2020-09-20
  • Sensitive fluorescence detection of SARS-CoV-2 RNA in clinical samples via one-pot isothermal ligation and transcription.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-18
    Chang Ha Woo,Sungho Jang,Giyoung Shin,Gyoo Yeol Jung,Jeong Wook Lee

    The control of viral outbreaks requires nucleic acid diagnostic tests that are sensitive, simple and fast. Here, we report a highly sensitive and specific one-pot assay for the fluorescence-based detection of RNA from pathogens. The assay, which can be performed within 30–50 min of incubation time and can reach a limit of detection of 0.1-attomolar RNA concentration, relies on a sustained isothermal

    更新日期:2020-09-20
  • Author Correction: Reclassifying neurodegenerative diseases.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-17
    Pablo Villoslada,Ricardo Baeza-Yates,Joseph C Masdeu

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-18
  • The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-14
    Ranjan Batra,David A Nelles,Daniela M Roth,Florian Krach,Curtis A Nutter,Takahiro Tadokoro,James D Thomas,Łukasz J Sznajder,Steven M Blue,Haydee L Gutierrez,Patrick Liu,Stefan Aigner,Oleksandr Platoshyn,Atsushi Miyanohara,Martin Marsala,Maurice S Swanson,Gene W Yeo

    Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3′ untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated RNA targeting, yet evidence of its in vivo efficacy and durability is lacking. Here, using adult and neonatal mouse

    更新日期:2020-09-14
  • Make the data available.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-10

    Obtaining valuable datasets is often arduous, costly and time-consuming. Give them away for wider reuse.

    更新日期:2020-09-11
  • Bioprinting within live animals.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-10
    Mark W Tibbitt

    Biomaterial structures can be printed with near-infrared light within the tissues of living animals by using photosensitive polymer hydrogels.

    更新日期:2020-09-11
  • Culturing homogeneous microtissues at scale.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-10
    R Jarrett Bliton,Scott T Magness

    Microwell arrays enable the culture of thousands of organoids with increased homogeneity, and facilitate high-content image-based analyses and high-throughput drug screens.

    更新日期:2020-09-11
  • An oral bacterial cocktail for kidney protection.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-10
    John Jarman,Dylan Dodd

    The oral delivery of a microencapsulated bacterial cocktail into animal models of kidney disease promotes the degradation of nitrogenous waste in the gut, thereby supporting renal function.

    更新日期:2020-09-11
  • Gelling hypotonic polymer solution for extended topical drug delivery to the eye.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-07
    Yoo Chun Kim,Matthew D Shin,Sean F Hackett,Henry T Hsueh,Raquel Lima E Silva,Abhijit Date,Hyounkoo Han,Byung-Jin Kim,Amy Xiao,Youngwook Kim,Laolu Ogunnaike,Nicole M Anders,Avelina Hemingway,Ping He,Albert S Jun,Peter J McDonnell,Charles Eberhart,Ian Pitha,Donald J Zack,Peter A Campochiaro,Justin Hanes,Laura M Ensign

    Eye-drop formulations should hold as high a concentration of soluble drug in contact with ocular epithelium for as long as possible. However, eye tears and frequent blinking limit drug retention on the ocular surface, and gelling drops typically form clumps that blur vision. Here, we describe a gelling hypotonic solution containing a low concentration of a thermosensitive triblock copolymer for extended

    更新日期:2020-09-08
  • Catheter-integrated soft multilayer electronic arrays for multiplexed sensing and actuation during cardiac surgery.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-09-07
    Mengdi Han,Lin Chen,Kedar Aras,Cunman Liang,Xuexian Chen,Hangbo Zhao,Kan Li,Ndeye Rokhaya Faye,Bohan Sun,Jae-Hwan Kim,Wubin Bai,Quansan Yang,Yuhang Ma,Wei Lu,Enming Song,Janice Mihyun Baek,Yujin Lee,Clifford Liu,Jeffrey B Model,Guanjun Yang,Roozbeh Ghaffari,Yonggang Huang,Igor R Efimov,John A Rogers

    The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with

    更新日期:2020-09-08
  • Clinical validation of a Cas13-based assay for the detection of SARS-CoV-2 RNA.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-26
    Maturada Patchsung,Krittapas Jantarug,Archiraya Pattama,Kanokpol Aphicho,Surased Suraritdechachai,Piyachat Meesawat,Khomkrit Sappakhaw,Nattawat Leelahakorn,Theerawat Ruenkam,Thanakrit Wongsatit,Niracha Athipanyasilp,Bhumrapee Eiamthong,Benya Lakkanasirorat,Thitima Phoodokmai,Nootaree Niljianskul,Danaya Pakotiprapha,Sittinan Chanarat,Aimorn Homchan,Ruchanok Tinikul,Philaiwarong Kamutira,Kochakorn Phiwkaow

    Nucleic acid detection by isothermal amplification and the collateral cleavage of reporter molecules by CRISPR-associated enzymes is a promising alternative to quantitative PCR. Here, we report the clinical validation of the specific high-sensitivity enzymatic reporter unlocking (SHERLOCK) assay using the enzyme Cas13a from Leptotrichia wadei for the detection of severe acute respiratory syndrome coronavirus

    更新日期:2020-08-26
  • Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-17
    Ling Li,Jianhua Zou,Yunlu Dai,Wenpei Fan,Gang Niu,Zhen Yang,Xiaoyuan Chen

    Cancer immunotherapies, particularly therapeutic vaccination, do not typically generate robust anti-tumour immune responses. Here, we show that the intratumoral burst release of the protein annexin A5 from intravenously injected hollow mesoporous nanoparticles made of diselenide-bridged organosilica generates robust anti-tumour immunity by exploiting the capacity of primary tumours to act as antigen

    更新日期:2020-08-17
  • In vivo tracking of single cells with PET.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-10
    Guus A M S van Dongen,Ronald Boellaard,Danielle J Vugts

    Positron emission tomography enables the tracking, in a mouse, of an intravenously injected cell radiolabelled with mesoporous silica nanoparticles containing 68Ga.

    更新日期:2020-08-10
  • Detecting liver disease via an endogenous pigment.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-10
    Justin J O'Sullivan,Nathaniel H O Harder,Marie C Heffern

    Lipofuscin, an endogenous pigment, can be used as a near-infrared fluorescent biomarker to stage and to monitor the progression of chronic liver disease, as shown in mice with induced liver disease and in human livers biopsied from patients with liver fibrosis.

    更新日期:2020-08-10
  • Long-term viability through selective permeability.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-10
    Ken Coppieters,Louise Winkel,Matthias von Herrath

    The cell-selective permeability of a retrievable microporous device encapsulating human therapeutic cells and implanted in the intraperitoneal space of mice provides long-term protection to the transplanted cells by dampening foreign-body responses and preventing the immune rejection of the graft.

    更新日期:2020-08-10
  • Tumour sensitization via the extended intratumoural release of a STING agonist and camptothecin from a self-assembled hydrogel.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-10
    Feihu Wang,Hao Su,Dongqing Xu,Wenbing Dai,Weijie Zhang,Zongyuan Wang,Caleb F Anderson,Mengzhen Zheng,Richard Oh,Fengyi Wan,Honggang Cui

    Tumours with an immunosuppressive microenvironment respond poorly to therapy. Activation of the stimulator of interferon genes (STING) pathway can enhance intratumoural immune activation, but STING agonists are associated with high toxicity and degrade prematurely, which limits their effectiveness. Here, we show that the extended intratumoural release of the STING agonist cyclic di-AMP transforms the

    更新日期:2020-08-10
  • Fast-and-fit vaccines.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-10

    Results from the early trials of vaccine candidates against SARS-CoV-2 signal the fitness of vaccine technologies soon to be tested at scale.

    更新日期:2020-08-06
  • Reclassifying neurodegenerative diseases.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-03
    Pablo Villoslada,Ricardo Baeza-Yates,Joseph C Masdeu

    Neuropathologies can be classified, on the basis of post-mortem histopathology and by using machine learning, into six transdiagnostic clusters associated with clinical phenotypes.

    更新日期:2020-08-03
  • Defining and predicting transdiagnostic categories of neurodegenerative disease.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-03
    Eli J Cornblath,John L Robinson,David J Irwin,Edward B Lee,Virginia M-Y Lee,John Q Trojanowski,Danielle S Bassett

    The prevalence of concomitant proteinopathies and heterogeneous clinical symptoms in neurodegenerative diseases hinders the identification of individuals who might be candidates for a particular intervention. Here, by applying an unsupervised clustering algorithm to post-mortem histopathological data from 895 patients with degeneration in the central nervous system, we show that six non-overlapping

    更新日期:2020-08-03
  • Power-saving design opportunities for wireless intracortical brain-computer interfaces.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-03
    Nir Even-Chen,Dante G Muratore,Sergey D Stavisky,Leigh R Hochberg,Jaimie M Henderson,Boris Murmann,Krishna V Shenoy

    The efficacy of wireless intracortical brain–computer interfaces (iBCIs) is limited in part by the number of recording channels, which is constrained by the power budget of the implantable system. Designing wireless iBCIs that provide the high-quality recordings of today’s wired neural interfaces may lead to inadvertent over-design at the expense of power consumption and scalability. Here, we report

    更新日期:2020-08-03
  • Integrated pipeline for the accelerated discovery of antiviral antibody therapeutics.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-08-03
    Pavlo Gilchuk,Robin G Bombardi,Jesse H Erasmus,Qing Tan,Rachel Nargi,Cinque Soto,Peter Abbink,Todd J Suscovich,Lorellin A Durnell,Amit Khandhar,Jacob Archer,Jenny Liang,Mallorie E Fouch,Edgar Davidson,Benjamin J Doranz,Taylor Jones,Elise Larson,Stacey Ertel,Brian Granger,Jasmine Fuerte-Stone,Vicky Roy,Thomas Broge,Thomas C Linnekin,Caitlyn H Linde,Matthew J Gorman,Joseph Nkolola,Galit Alter,Steven

    The emergence and re-emergence of highly virulent viral pathogens with the potential to cause a pandemic creates an urgent need for the accelerated discovery of antiviral therapeutics. Antiviral human monoclonal antibodies (mAbs) are promising candidates for the prevention and treatment of severe viral diseases, but their long development timeframes limit their rapid deployment and use. Here, we report

    更新日期:2020-08-03
  • Classification of T-cell activation via autofluorescence lifetime imaging.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-27
    Alex J Walsh,Katherine P Mueller,Kelsey Tweed,Isabel Jones,Christine M Walsh,Nicole J Piscopo,Natalie M Niemi,David J Pagliarini,Krishanu Saha,Melissa C Skala

    The function of a T cell depends on its subtype and activation state. Here, we show that imaging of the autofluorescence lifetime signals of quiescent and activated T cells can be used to classify the cells. T cells isolated from human peripheral blood and activated in culture using tetrameric antibodies against the surface ligands CD2, CD3 and CD28 showed specific activation-state-dependent patterns

    更新日期:2020-07-27
  • Tracking the expression of therapeutic protein targets in rare cells by antibody-mediated nanoparticle labelling and magnetic sorting.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-27
    Mahmoud Labib,Zongjie Wang,Sharif U Ahmed,Reza M Mohamadi,Bill Duong,Brenda Green,Edward H Sargent,Shana O Kelley

    Molecular-level features of tumours can be tracked using single-cell analyses of circulating tumour cells (CTCs). However, single-cell measurements of protein expression for rare CTCs are hampered by the presence of a large number of non-target cells. Here, we show that antibody-mediated labelling of intracellular proteins in the nucleus, mitochondria and cytoplasm of human cells with magnetic nanoparticles

    更新日期:2020-07-27
  • A low-power band of neuronal spiking activity dominated by local single units improves the performance of brain-machine interfaces.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-27
    Samuel R Nason,Alex K Vaskov,Matthew S Willsey,Elissa J Welle,Hyochan An,Philip P Vu,Autumn J Bullard,Chrono S Nu,Jonathan C Kao,Krishna V Shenoy,Taekwang Jang,Hun-Seok Kim,David Blaauw,Parag G Patil,Cynthia A Chestek

    The large power requirement of current brain–machine interfaces is a major hindrance to their clinical translation. In basic behavioural tasks, the downsampled magnitude of the 300–1,000 Hz band of spiking activity can predict movement similarly to the threshold crossing rate (TCR) at 30 kilo-samples per second. However, the relationship between such a spiking-band power (SBP) and neural activity remains

    更新日期:2020-07-27
  • Purification of protein therapeutics via high-affinity supramolecular host-guest interactions.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-20
    Jaeyeon An,Sungwan Kim,Annadka Shrinidhi,Junghyun Kim,Hasanul Banna,Gihyun Sung,Kyeng Min Park,Kimoon Kim

    Efficient purification is crucial to providing large quantities of recombinant therapeutic proteins, such as monoclonal antibodies and cytokines. However, affinity techniques for manufacturing protein therapeutics that use biomolecule-conjugated agarose beads that harness specific biomolecular interactions suffer from issues related to protein denaturation, contamination and the need to maintain biomolecule-specific

    更新日期:2020-07-20
  • Theranostic multimodal gold nanoclusters.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-13
    Gang He,Peng Huang,Xiaoyuan Chen

    Gold nanoclusters stabilized by the milk metalloprotein α-lactalbumin and displaying multicolour and multimodal fluorescence aid the detection, resection and treatment of breast tumours in mice.

    更新日期:2020-07-13
  • Trust, but thoroughly verify.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-13

    Two recent high-profile retractions of COVID-19 papers exemplify that trust cannot be taken for granted. To strengthen it, scientfic review will have to become more transparent.

    更新日期:2020-07-13
  • From unstable input to robust output.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-13
    Lahiru N Wimalasena,Lee E Miller,Chethan Pandarinath

    In the presence of recording instabilities, the performance of brain–computer interfaces can be robustly maintained by exploiting ‘hidden’ structures underlying neural activity.

    更新日期:2020-07-13
  • Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-13
    Uros Kuzmanov,Erika Yan Wang,Rachel Vanderlaan,Da Hye Kim,Shin-Haw Lee,Sina Hadipour-Lakmehsari,Hongbo Guo,Yimu Zhao,Meghan McFadden,Parveen Sharma,Filio Billia,Milica Radisic,Anthony Gramolini,Andrew Emili

    Study of the molecular basis of myocardial fibrosis is hampered by limited access to tissues from human patients and by confounding variables associated with sample accessibility, collection, processing and storage. Here, we report an integrative strategy based on mass spectrometry for the phosphoproteomic profiling of normal and fibrotic cardiac tissue obtained from surgical explants from patients

    更新日期:2020-07-13
  • Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-13
    Jiang Yang,Tai Wang,Lina Zhao,Vinagolu K Rajasekhar,Suhasini Joshi,Chrysafis Andreou,Suchetan Pal,Hsiao-Ting Hsu,Hanwen Zhang,Ivan J Cohen,Ruimin Huang,Ronald C Hendrickson,Matthew M Miele,Wenbo Pei,Matthew B Brendel,John H Healey,Gabriela Chiosis,Moritz F Kircher

    Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent ultrasmall gold quantum clusters that are stabilized by the milk metalloprotein alpha-lactalbumin. We synthesized three types of these nanoprobes that together display fluorescence across the visible and near-infrared spectra when excited

    更新日期:2020-07-13
  • Erythrocyte depletion lifts nanoparticle half-lives.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-06
    Horacio Cabral,Kazunori Kataoka

    The partial depletion of red blood cells via the administration of a low dose of anti-erythrocyte antibodies increases the circulation half-life of nanomedicines, as shown in rodent models of cancer.

    更新日期:2020-07-06
  • Enhancement of the blood-circulation time and performance of nanomedicines via the forced clearance of erythrocytes.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-06
    Maxim P Nikitin,Ivan V Zelepukin,Victoria O Shipunova,Ilya L Sokolov,Sergey M Deyev,Petr I Nikitin

    The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg−1) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of

    更新日期:2020-07-06
  • Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-06
    Yunfeng Gao,Hui Zhang,Nannan Zhou,Pingwei Xu,Jianxiong Wang,Yuan Gao,Xun Jin,Xiaoyu Liang,Jiadi Lv,Yamin Zhang,Ke Tang,Jingwei Ma,Huafeng Zhang,Jing Xie,Fang Yao,Weimin Tong,Yuying Liu,Ximo Wang,Bo Huang

    Most patients with cholangiocarcinoma (CCA) develop extrahepatic malignant biliary obstructions, which require palliative drainage to normalize bilirubin levels and to improve the patients’ overall survival. Here, we report that the infusion of methotrexate-containing plasma-membrane microvesicles derived from apoptotic human tumour cells into the bile-duct lumen of patients with extrahepatic CCA mobilized

    更新日期:2020-07-06
  • An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-07-06
    Di-Wei Zheng,Pei Pan,Ke-Wei Chen,Jin-Xuan Fan,Chu-Xin Li,Han Cheng,Xian-Zheng Zhang

    Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota

    更新日期:2020-07-06
  • Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-29
    Ian S Kinstlinger,Sarah H Saxton,Gisele A Calderon,Karen Vasquez Ruiz,David R Yalacki,Palvasha R Deme,Jessica E Rosenkrantz,Jesse D Louis-Rosenberg,Fredrik Johansson,Kevin D Janson,Daniel W Sazer,Saarang S Panchavati,Karl-Dimiter Bissig,Kelly R Stevens,Jordan S Miller

    Sacrificial templates for patterning perfusable vascular networks in engineered tissues have been constrained in architectural complexity, owing to the limitations of extrusion-based 3D printing techniques. Here, we show that cell-laden hydrogels can be patterned with algorithmically generated dendritic vessel networks and other complex hierarchical networks by using sacrificial templates made from

    更新日期:2020-06-29
  • Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-29
    Nobuyuki Tanaka,Shigeaki Kanatani,Dagmara Kaczynska,Keishiro Fukumoto,Lauri Louhivuori,Tomohiro Mizutani,Oded Kopper,Pauliina Kronqvist,Stephanie Robertson,Claes Lindh,Lorand Kis,Robin Pronk,Naoya Niwa,Kazuhiro Matsumoto,Mototsugu Oya,Ayako Miyakawa,Anna Falk,Johan Hartman,Cecilia Sahlgren,Hans Clevers,Per Uhlén

    Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimodal

    更新日期:2020-06-29
  • Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-22
    Suping Li,Yinlong Zhang,Shih-Hsin Ho,Bozhao Li,Meifang Wang,Xiongwei Deng,Na Yang,Guangna Liu,Zefang Lu,Junchao Xu,Quanwei Shi,Jing-Yan Han,Lirong Zhang,Yan Wu,Yuliang Zhao,Guangjun Nie

    Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles

    更新日期:2020-06-23
  • Integrating spatial gene expression and breast tumour morphology via deep learning.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-22
    Bryan He,Ludvig Bergenstråhle,Linnea Stenbeck,Abubakar Abid,Alma Andersson,Åke Borg,Jonas Maaskola,Joakim Lundeberg,James Zou

    Spatial transcriptomics allows for the measurement of RNA abundance at a high spatial resolution, making it possible to systematically link the morphology of cellular neighbourhoods and spatially localized gene expression. Here, we report the development of a deep learning algorithm for the prediction of local gene expression from haematoxylin-and-eosin-stained histopathology images using a new dataset

    更新日期:2020-06-23
  • Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-22
    Mari Saif,Wilhelmus J Kwanten,Jessica A Carr,Ivy X Chen,Jessica M Posada,Amitabh Srivastava,Juanye Zhang,Yi Zheng,Matthias Pinter,Sampurna Chatterjee,Samir Softic,C Ronald Kahn,Klaus van Leyen,Oliver T Bruns,Rakesh K Jain,Moungi G Bawendi

    Monitoring the progression of non-alcoholic fatty liver disease is hindered by a lack of suitable non-invasive imaging methods. Here, we show that the endogenous pigment lipofuscin displays strong near-infrared and shortwave-infrared fluorescence when excited at 808 nm, enabling label-free imaging of liver injury in mice and the discrimination of pathological processes from normal liver processes with

    更新日期:2020-06-23
  • Dense anatomical annotation of slit-lamp images improves the performance of deep learning for the diagnosis of ophthalmic disorders.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-22
    Wangting Li,Yahan Yang,Kai Zhang,Erping Long,Lin He,Lei Zhang,Yi Zhu,Chuan Chen,Zhenzhen Liu,Xiaohang Wu,Dongyuan Yun,Jian Lv,Yizhi Liu,Xiyang Liu,Haotian Lin

    The development of artificial intelligence algorithms typically demands abundant high-quality data. In medicine, the datasets that are required to train the algorithms are often collected for a single task, such as image-level classification. Here, we report a workflow for the segmentation of anatomical structures and the annotation of pathological features in slit-lamp images, and the use of the workflow

    更新日期:2020-06-23
  • Intravital three-dimensional bioprinting.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-22
    Anna Urciuolo,Ilaria Poli,Luca Brandolino,Paolo Raffa,Valentina Scattolini,Cecilia Laterza,Giovanni G Giobbe,Elisa Zambaiti,Giulia Selmin,Michael Magnussen,Laura Brigo,Paolo De Coppi,Stefano Salmaso,Monica Giomo,Nicola Elvassore

    Fabrication of three-dimensional (3D) structures and functional tissues directly in live animals would enable minimally invasive surgical techniques for organ repair or reconstruction. Here, we show that 3D cell-laden photosensitive polymer hydrogels can be bioprinted across and within tissues of live mice, using bio-orthogonal two-photon cycloaddition and crosslinking of the polymers at wavelengths

    更新日期:2020-06-22
  • Author Correction: Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-16
    Chun Loong Ho,Hui Qing Tan,Koon Jiew Chua,Aram Kang,Kiat Hon Lim,Khoon Lin Ling,Wen Shan Yew,Yung Seng Lee,Jean Paul Thiery,Matthew Wook Chang

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-16
  • Whole-body tracking of single cells via positron emission tomography.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-15
    Kyung Oh Jung,Tae Jin Kim,Jung Ho Yu,Siyeon Rhee,Wei Zhao,Byunghang Ha,Kristy Red-Horse,Sanjiv Sam Gambhir,Guillem Pratx

    In vivo molecular imaging can measure the average kinetics and movement routes of injected cells through the body. However, owing to non-specific accumulation of the contrast agent and its efflux from the cells, most of these imaging methods inaccurately estimate the distribution of the cells. Here, we show that single human breast cancer cells loaded with mesoporous silica nanoparticles concentrating

    更新日期:2020-06-15
  • COVID-19 remedies.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-12

    Repurposed drugs, inhibitors of inflammatory cytokines, neutralizing monoclonal antibodies and sera from convalescent patients will help ease the burden of COVID-19 on healthcare systems.

    更新日期:2020-06-12
  • Detection of bacterial infection via a fidget spinner.
    Nat. Biomed. Eng. (IF 18.952) Pub Date : 2020-06-12
    Hui Li,Peter Torab,Pak Kin Wong

    A custom fidget spinner that uses centrifugal forces to concentrate bacterial pathogens in urine samples enables the rapid on-device colorimetric detection of urinary tract infections and the testing of the pathogen’s susceptibility to antibiotics.

    更新日期:2020-06-12
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