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| Open AccessHigh-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cell surface mechanics remains largely unexplored at single-cell resolution. Here, the authors report a high-throughput single-cell assay, ELASTomics, which integrates mechanical phenotyping with unbiased transcriptomics.
- Akifumi Shiomi
- , Taikopaul Kaneko
- & Hirofumi Shintaku
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Article
| Open AccessDynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy
Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.
- Maxime Mistretta
- , Mena Cimino
- & Giulia Manina
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Article
| Open AccessE-cardiac patch to sense and repair infarcted myocardium
Infarted myocardium hampers the synchronous electroactivity of the cardiac tissue. Here, the authors showcase a battery-free conductive cardiac patch made of reduced graphene and its therapeutic efficacy for cardiac repair.
- Renjie Qiu
- , Xingying Zhang
- & Leyu Wang
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Article
| Open AccessRegulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles
Despite advances in active drug-targeting for blood-brain barrier penetration, challenges related to brain biodistribution, and drug accumulation persist. Here the authors show a molecular library design centered on cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system inspired by the neuroprotective properties of vinpocetine.
- Xufei Bian
- , Ling Yang
- & Chong Li
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Matters Arising
| Open AccessReply to: Technical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications
- Kai Liu
- , Elisa Lázaro-Ibáñez
- & Alan Sabirsh
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Article
| Open AccessImplication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature
The role of subcellular thermogenesis during neuronal differentiation remains poorly understood. Here, the authors employ methods to monitor local intracellular temperature, and they investigate the effects of non-invasive temperature changes on cell differentiation using neuron-like cells.
- Shunsuke Chuma
- , Kazuyuki Kiyosue
- & Yoshie Harada
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Article
| Open AccessA genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution
The ubiquitous second messenger c-di-GMP regulates many biological processes in bacteria, including cell cycle, motility, virulence and biofilm formation. Here, Kaczmarczyk et al. develop a c-di-GMP biosensor that enables dynamic real-time tracking of c-di-GMP levels in individual living cells.
- Andreas Kaczmarczyk
- , Simon van Vliet
- & Urs Jenal
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Article
| Open AccessChiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination
Radiation-induced tumor vaccination is insufficient to elicit robust antitumor immune response. Here they combine chiral vidarabine monophosphate-gadolinium nanowires with immune checkpoint blockade therapy to synergistically induce antitumor immunity.
Reviewer recognition:
- Zhusheng Huang
- , Rong Gu
- & Ahu Yuan
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Review Article
| Open AccessCritical learning from industrial catalysis for nanocatalytic medicine
The knowledge gained from industrial catalysis benefits advancements of nanocatalytic medicines. Here the authors review the similarities, differences and connections in catalytic reactions between industrial and medical applications to support deep understanding and rational design of nanocatalytic medicines.
- Zhaokui Jin
- , Lingdong Jiang
- & Qianjun He
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Article
| Open AccessCell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting
Molecular recognition of proteins is essential for achieving their biological functions but it is challenging to prepare selective protein-binding materials. Here the authors report a method that combines dynamic covalent chemistry and double molecular imprinting to construct protein-recognizing nanoparticles capable of specific inhibition of protein–protein interactions.
- Avijit Ghosh
- , Mansi Sharma
- & Yan Zhao
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Article
| Open AccessDevelopment of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy
The development of metal-nucleic acid nanocomposites for therapeutic is limited by poor stability and synthesis efficiency. Here, the authors develop a multi-fragmented aptamer DNAzyme metal-nucleic acid frameworks (MNFs) under milder conditions and demonstrate its preclinical efficacy in gastric cancer.
- Jiaqi Yan
- , Rajendra Bhadane
- & Hongbo Zhang
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Article
| Open AccessBiocomposite thermoplastic polyurethanes containing evolved bacterial spores as living fillers to facilitate polymer disintegration
Plastic pollution severely threatens the resilience of nature. Here, the authors utilize the spore-forming, polymer-degrading bacteria, Bacillus subtilis, as a living filler to develop biocomposite thermoplastic polyurethane with improved mechanical properties and biodegradation.
- Han Sol Kim
- , Myung Hyun Noh
- & Jonathan K. Pokorski
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Article
| Open AccessIn situ enzymatic control of colloidal phoresis and catalysis through hydrolysis of ATP
The design of synthetic systems that can sense chemical gradients and respond with directional motility and chemical activity is of interest. Here, the authors realize and control such behaviors in a synthetic system by tailoring multivalent interactions of adenosine nucleotides with catalytic microbeads.
- Ekta Shandilya
- , Bhargav Rallabandi
- & Subhabrata Maiti
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Article
| Open AccessStimulus-responsive assembly of nonviral nucleocapsids
A stimulus-responsive approach for recapitulating nonviral nucleocapsid assembly on demand under controlled conditions provides a robust platform for applications in synthetic biology and mRNA nanomedicine.
- Mao Hori
- , Angela Steinauer
- & Donald Hilvert
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Article
| Open AccessUltrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
The recent monkeypox outbreak highlighted the need for rapid and accurate diagnosis of this disease. Here, authors develop an ultrasensitive and streamlined CRISPR assay using miniaturized device, which can detect monkeypox virus in rash fluid swab, oral swab, saliva, and urine within 15 minutes.
- Yunxiang Wang
- , Hong Chen
- & Shengqi Wang
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Article
| Open AccessAssembly of short amphiphilic peptoids into nanohelices with controllable supramolecular chirality
Helical protein assemblies are an important biological structure, but are challenging to mimic with synthetic materials. Here, the authors report the use of peptoids to form nanohelix structures with controllable supramolecular chirality.
- Renyu Zheng
- , Mingfei Zhao
- & Chun-Long Chen
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Article
| Open AccessContext-aware deep learning enables high-efficacy localization of high concentration microbubbles for super-resolution ultrasound localization microscopy
Ultrasound localisation microscopy enables deep tissue microvascular imaging. Here, authors introduce LOCA-ULM, a deep learning pipeline enhancing localisation accuracy in high microbubble concentrations. LOCA-ULM reveals dense cerebrovascular networks and enhances the sensitivity of functional ULM.
- YiRang Shin
- , Matthew R. Lowerison
- & Pengfei Song
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Review Article
| Open AccessArtificial cells for in vivo biomedical applications through red blood cell biomimicry
Despite the enormous progress in the field of giant lipid vesicles, their use for in vivo biomedical applications is limited. Here, the authors discuss red blood cells as inspiration for enhancing those vesicles, investigating the required cellular features and the corresponding technical hurdles.
- Jorik Waeterschoot
- , Willemien Gosselé
- & Xavier Casadevall i Solvas
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Article
| Open AccessLanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo
The strong scattering of biological tissue causes challenges when monitoring temperature changes at the microscale. Here, the authors propose a nanothermometer based on lanthanide luminescence, enabling minimally invasive imaging of the cerebrovascular system of mice at nearly 200 μm resolution.
- Yukai Wu
- , Fang Li
- & Xingjun Zhu
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Article
| Open AccessEngineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages
Here the authors describe a stabilization technology that engineers crosslinks between tyrosine sidechains into a natively folded vaccine immunogen and show that immunogenicity is improved in small animal models by locking the most potently neutralizing epitopes.
- Sonal V. Gidwani
- , Devarshi Brahmbhatt
- & Mark A. Yondola
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Article
| Open AccessIdentifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer. Here, authors develop a dual endogenous reporter system to identify functional regulators of aberrant stem cell and differentiation programs, showing that SMARCB1 restricts differentiation, and nominating other regulators with therapeutic potential.
- Sandor Spisak
- , David Chen
- & Nilay S. Sethi
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Article
| Open AccessBioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2
The main protease (Mpro) plays a crucial role in the replication of SARS-CoV-2, thereby making it an attractive target for COVID-19 treatment. Here, the authors develop a colorimetric screening platform for discovering Mpro inhibitors using engineered amyloid peptide-based nanocomplexes.
- Dongtak Lee
- , Hyo Gi Jung
- & Dae Sung Yoon
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Article
| Open AccessCholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery
Cholesterol (Chol) transfer from lipid bilayer jeopardizes membrane stability and causes premature payload leakage, yielding suboptimal efficacy. Here, the authors report a Chol-modified sphingomyelin (SM) bilayer via covalently conjugating Chol to SM, which retains Chol condensing ability and improves pharmacokinetics and therapeutic delivery of various drugs in diverse disease animal models.
- Zhiren Wang
- , Wenpan Li
- & Jianqin Lu
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Article
| Open AccessRectifying artificial nanochannels with multiple interconvertible permeability states
Transmembrane channels have inspired the development of biomimetic channels. Here, the authors present a class of artificial nanochannels based on DNAzyme-functionalized glass nanopipettes to allow for the control of channel permeability.
- Ruocan Qian
- , Mansha Wu
- & Yi Lu
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Article
| Open AccessAn artificial protein modulator reprogramming neuronal protein functions
Direct modulation of protein by artificial catalysts as enzyme mimetics remains hindered by the lack of highly efficient catalytic centers. Here, the authors present the development of artificial protein modulators (APROMs) with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein.
- Peihua Lin
- , Bo Zhang
- & Daishun Ling
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Article
| Open AccessNanopore analysis of salvianolic acids in herbal medicines
Natural herbs, which contain pharmacologically active compounds, have been historically used as medicines but the analysis of their chemical components is time-consuming and complex. Here, the authors report a phenylboronic acid appended Mycobacterium smegmatis porin A (MspA) nanopore for sensing a variety of bioactive compounds based on salvianolic acid, without the need for sample separation or purification.
- Pingping Fan
- , Shanyu Zhang
- & Shuo Huang
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Article
| Open AccessNanopore analysis of cis-diols in fruits
Fruits contain a large variety of cis-diols but their rapid and direct analysis without complex sample pretreatment was not achieved. Here, the authors report a Mycobacterium smegmatis porin A nanopore modified with a phenylboronic acid adapter for recognition of 1,2-diphenols, alditols, α-hydroxy acids and saccharides in fruits.
- Pingping Fan
- , Zhenyuan Cao
- & Shuo Huang
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Article
| Open AccessDynamic control of DNA condensation
Artificial biomolecular condensates are valuable tools to study the design principles of phase separation. Here, the authors demonstrate and characterize a model system of artificial DNA condensates whose kinetic formation and dissolution depends on DNA inputs that activate or deactivate the phase separating DNA subunits.
- Siddharth Agarwal
- , Dino Osmanovic
- & Elisa Franco
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Article
| Open AccessHigh-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models
Identifying pulmonary delivery of lipid libraries poses an obstacle for mRNA drugs. Here, the authors use a barcoded screening system to identify lung-targeting of cationic, degradable lipid-like materials for mRNA delivery and gene editing in female preclinical models.
- Lulu Xue
- , Alex G. Hamilton
- & Michael J. Mitchell
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Article
| Open AccessIn situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors
Branched ionizable lipids have aroused great interest for mRNA delivery. Here, the authors devise an in situ construction method for combinatorial synthesis of degradable branched ionizable lipids and summarize key design criteria to enable potent delivery of mRNA therapeutics and gene editors.
- Xuexiang Han
- , Junchao Xu
- & Michael J. Mitchell
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Article
| Open AccessSingle-molecule RNA sizing enables quantitative analysis of alternative transcription termination
The development of RNA technologies demands accurate assessment of transcript size and heterogeneity. Here, authors report a nanopore-based approach to study full-length RNA transcripts at the single-molecule level, identify premature transcription termination and study rolling-circle transcription.
- Gerardo Patiño-Guillén
- , Jovan Pešović
- & Ulrich Felix Keyser
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Article
| Open AccessCreation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration
Low-cost point-of-care sensors are vital for precision medicine. Here, the authors have repurposed a glucometer for breast cancer therapeutic detection capable of sensing tamoxifen in human blood, utilizing blood glucose to power and amplify the therapeutic signals
- Rong Cai
- , Chiagoziem Ngwadom
- & Caroline M. Ajo-Franklin
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Article
| Open AccessBlack phosphorus boosts wet-tissue adhesion of composite patches by enhancing water absorption and mechanical properties
The utility of wet-tissue adhesives has been impeded by the suboptimal adhesive strength. Here the authors report a composite patch integrated with BP nanosheets that improve the wet-tissue adhesion by enhancing the water absorption and mechanical properties of the patch and demonstrate the uses of the patch in hemostasis, physical-activity monitoring and tumour-recurrence prevention.
- Yuanchi Zhang
- , Cairong Li
- & Yuxiao Lai
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Article
| Open AccessA hybrid transistor with transcriptionally controlled computation and plasticity
Interfacing living systems with electronics for biosensing and biocomputing applications is challenging. Here, Gao et al. present hybrid transistors with electroactive bacteria capable of extracellular electron transfer, enabling transduction of biological computations to electrical readouts.
- Yang Gao
- , Yuchen Zhou
- & Benjamin K. Keitz
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Article
| Open AccessA microfluidic platform integrating functional vascularized organoids-on-chip
Vascularization remains a significant challenge in organoid technology. Here, the authors develop a microfluidic platform that enhances organoid growth, function and maturation, by establishing functional perfusable vascular networks.
- Clément Quintard
- , Emily Tubbs
- & Xavier Gidrol
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Article
| Open AccessBiporous silica nanostructure-induced nanovortex in microfluidics for nucleic acid enrichment, isolation, and PCR-free detection
Efficient enrichment and isolation of pathogens are crucial for accurate and sensitive disease identification. Here, the authors present a chip equipped with biporous nanofilms that induces a nanovetex in a microfluidic channel for nucleic acid enrichment, isolation, and detection.
- Eunyoung Jeon
- , Bonhan Koo
- & Joonseok Lee
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Article
| Open AccessModeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip
Here the authors develop perfusable inner blood-retinal barrier-specific microvascular networks with human primary retinal microvascular cells. They show that chronic diabetic stimulation leads to the generation of early hallmarks of diabetic retinopathy, including pericyte and capillary dropout, ghost vessels, and inflammation.
- Thomas L. Maurissen
- , Alena J. Spielmann
- & Héloïse Ragelle
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Article
| Open AccessBroad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine
Evolution of SARS-CoV-2 and emergence of other sarbecoviruses are of potential concern. Here, the authors designed a trivalent spike-protein-nanoparticle vaccine that elicits neutralizing antibodies and protects female hamsters against challenges with SARS-CoV-2-like and SARS-CoV-1-like coronaviruses.
- Peter J. Halfmann
- , Kathryn Loeffler
- & Ravi S. Kane
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Article
| Open AccessMicrometer-thick and porous nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties
It is vital but challenging to develop coating technologies for addressing reliability and durability issues of electrochemical sensors when exposed to diverse and complex biological environments. Here, the authors report a micrometer-thick, porous and robust nanocomposite coating that enables highly sensitive and stable electrochemical sensors.
- Jeong-Chan Lee
- , Su Yeong Kim
- & Donald E. Ingber
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Article
| Open AccessA genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice
Achieving genetic circuits on single DNA molecules could have varied applications. Here, authors observed proteins emerging from single DNA molecules through coupled transcription-translation complexes, and show that nascent proteins lingered on DNA, regulating cascaded reactions on the same DNA and allowing the design of a pulsatile genetic circuit.
- Ferdinand Greiss
- , Nicolas Lardon
- & Roy Bar-Ziv
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Article
| Open AccessA nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota
Here, the authors develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, to treat Helicobacter pylori.
- Tao Liu
- , Shuang Chai
- & Lihua Yang
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Article
| Open AccessRapid and visual identification of β-lactamase subtypes for precision antibiotic therapy
The rapid identification of drug-resistant bacteria is vital for effective treatment and to avoid antibiotic misuse. Here authors report a paper-based sensor which utilises chromogenic carbapenem and cephalosporin substrates for the identification and discrimination of β-lactamase subtypes.
- Wenshuai Li
- , Jingqi Li
- & Dingbin Liu
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Article
| Open AccessDNA mechanocapsules for programmable piconewton responsive drug delivery
The mechanical dysregulation of cells is associated with several diseases and strategies to deliver drugs based on the “mechanical phenotype” of a cell are desirable. Here, the authors design and characterize DNA mechanocapsules comprised of DNA tetrahedrons that are force responsive, and showed they can encapsulate macromolecular cargo and release it upon application of force.
- Arventh Velusamy
- , Radhika Sharma
- & Khalid Salaita
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Article
| Open AccessInterindividual- and blood-correlated sweat phenylalanine multimodal analytical biochips for tracking exercise metabolism
The in-depth study on the sweat–blood partitioning mechanisms of amino acids is promising for noninvasive metabolic monitoring. Here, the authors develop a wearable biochip for sweat phenylalanine multimodal analysis aimed at tracking exercise metabolic risk and exploring the sweat–blood correlation.
- Bowen Zhong
- , Xiaokun Qin
- & Lili Wang
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Article
| Open AccessSoluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force
The Notch receptor is known to be activated by a pulling force, but whether it is strictly required remains to be clarified. Here, the authors demonstrate activation of Notch through soluble multivalent DNA origami constructs, showing effects in neuroepithelial-like stem cells.
- Ioanna Smyrlaki
- , Ferenc Fördős
- & Björn Högberg
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Article
| Open AccessNanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.
- Lays Cordeiro Guimaraes
- , Pedro Augusto Carvalho Costa
- & Pedro Pires Goulart Guimaraes
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Article
| Open AccessFlexible, scalable, high channel count stereo-electrode for recording in the human brain
Electrodes available for deep brain recording and stimulation have a number of limitations. Here the authors describe a thin-film depth electrode that may offer improved spatial and temporal resolution for recording brain activity.
- Keundong Lee
- , Angelique C. Paulk
- & Shadi. A. Dayeh
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Article
| Open AccessSelf-propelled assembly of nanoparticles with self-catalytic regulation for tumour-specific imaging and therapy
In vivo manipulation of the dynamics of nanoparticles’ is essential for disease-specific imaging and therapy, but tends to involve complex design processes. Here, the authors report a strategy for manipulating the assembly of nanoparticles in vivo through a self-catalysis-instructed dimerization of tyrosine, offering convenient fabrication, high reaction specificity and biocompatibility.
- Mengmeng Xia
- , Qiyue Wang
- & Daishun Ling
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Article
| Open AccessNon-Faradaic optoelectrodes for safe electrical neuromodulation
Nanoscale optoelectrodes hold the potential to optically stimulate individual neuron. Here, the authors form nanoscale capacitive optoelectrodes by incorporating zinc porphyrin into nanorods, coated by TiO2, a design that allows for far-field optical modulation of neurons with efficiency and negligible side effects.
- Jian Chen
- , Yanyan Liu
- & Wenbo Bu