Featured
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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 AccessPROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics
Understanding biological mechanisms requires a thorough exploration of spatiotemporal transcriptional patterns in complex tissues. Here, authors present PROST to quantify spatial gene expression patterns and detect spatial domains using spatial transcriptomics data of varying resolutions.
- Yuchen Liang
- , Guowei Shi
- & Zhonghui Tang
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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 AccessEmbryos assist morphogenesis of others through calcium and ATP signaling mechanisms in collective teratogen resistance
The collective activity of cells enables embryos to overcome various perturbations. Here, authors show that at the higher (population) level, embryos also communicate. This enables larger groups to resist chemical and molecular-genetic teratogens.
- Angela Tung
- , Megan M. Sperry
- & Michael Levin
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Article
| Open AccessAntibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper
The recent emergence of monoclonal antibodies able to neutralize snake toxins have revolutionized the approach of developing novel therapies to treat snakebite envenoming, at least in animal models. Here, the authors show antibody-dependent enhancement of toxicity (ADET) for a toxin derived from snake venom and highlight the importance of this phenomenon when testing therapeutic antibodies against snake venoms in animal models.
- Christoffer V. Sørensen
- , Julián Fernández
- & Andreas H. Laustsen
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Article
| Open AccessEnhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation
Achieving targeted drug delivery for calcified aortic valve is challenging. Here, the authors find that protease activated receptor 2 (PAR2) is up-regulated on calcified valves and develop a magnetic nanocarrier functionalized with PAR2-targeting peptide for dual-active drug delivery.
- Jinyong Chen
- , Tanchen Ren
- & Xianbao Liu
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Article
| Open AccessReprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
Somatic cloning of rhesus monkey has not been successful until now. Here, authors report epigenetic abnormalities in SCNT embryos and placentas and develop a trophoblast replacement method that enables them to successful clone of a healthy male rhesus monkey.
- Zhaodi Liao
- , Jixiang Zhang
- & Qiang Sun
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Article
| Open AccessFlexible switch matrix addressable electrode arrays with organic electrochemical transistor and pn diode technology
Organic neural implants hold considerable promise for biocompatible neural interfaces. Here, the authors employ polymer-based organic electrochemical diodes and transistors to develop neuron-sized complex circuits, enabling multiplexing without crosstalk and demonstrate that, when integrated onto ultra-thin plastic, these circuits achieve high performance while maintaining minimal invasiveness.
- Ilke Uguz
- , David Ohayon
- & Kenneth L. Shepard
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Article
| Open AccessA self-powered intracardiac pacemaker in swine model
Harvesting biomechanical energy from cardiac motion is an attractive power source for implantable bioelectronic devices. Here, the authors report a battery-free, transcatheter, self-powered intracardiac pacemaker for the treatment of arrhythmia in large animal models.
- Zhuo Liu
- , Yiran Hu
- & Zhong Lin Wang
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Article
| Open AccessDigital automation of transdermal drug delivery with high spatiotemporal resolution
Microneedle patches that can actively address individual needles are challenging to realize. Here, the authors introduce a spatiotemporal on-demand patch for precise and personalized drug delivery, utilizing electrically triggered control with drug-loaded microneedles and biocompatible metallic membranes.
- Yihang Wang
- , Zeka Chen
- & Wubin Bai
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Article
| Open AccessBIDCell: Biologically-informed self-supervised learning for segmentation of subcellular spatial transcriptomics data
Subcellular in situ spatial transcriptomics offers the promise to address biological problems that were previously inaccessible but requires accurate cell segmentation to uncover insights. Here, authors present BIDCell, a biologically informed, deep learning-based cell segmentation framework.
- Xiaohang Fu
- , Yingxin Lin
- & Jean Y. H. Yang
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Article
| Open AccessDirect RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome
It can be difficult to find rare transcripts when sequencing a transcriptome. Here the authors show adaptive sampling on direct RNA runs to increase the likelihood of finding less frequent ones while selectively ejecting the higher-abundance transcripts.
- Jiaxu Wang
- , Lin Yang
- & Yue Wan
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Article
| Open AccessDe novo biosynthesis of antiarrhythmic alkaloid ajmaline
Ajmaline is an antiarrhythmic monoterpenoid indole alkaloid produced by the root of Rauwolfia serpentina. Here, the authors complete the ajmaline biosynthetic pathway by identifying two reductases and two esterases, and achieve the de novo ajmaline biosynthesis by engineering Baker’s yeast.
- Jun Guo
- , Di Gao
- & Yang Qu
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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 AccessCross-feeding promotes heterogeneity within yeast cell populations
Cellular heterogeneity in cell populations of isogenic origin is driven by diverse factors such as nutrient availability and interactions with neighbouring cells. Here, Hu et al. study plasmid retention dynamics in yeast populations, and show that the exchange of complementary metabolites between plasmid-carrying prototrophs and plasmid-free auxotrophs allows the latter to proliferate in selective environments.
- Kevin K. Y. Hu
- , Ankita Suri
- & Victoria S. Haritos
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Article
| Open AccessGene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
Homing-based gene drives are novel interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here the authors demonstrate the feasibility of a gene drive approach for the genetic control of the agricultural pest, the medfly, based on complete female-to-male sex conversion.
- Angela Meccariello
- , Shibo Hou
- & Nikolai Windbichler
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Article
| Open AccessSilica-associated proteins from hexactinellid sponges support an alternative evolutionary scenario for biomineralization in Porifera
Sponges, being early-diverging metazoans and the only animals to develop extensive skeletons of silica, have potential to inform about the evolutionary steps of metazoan traits, including biomineralization. Here, the authors characterize two proteins associated with the hexactinellid sponge silica.
- Katsuhiko Shimizu
- , Michika Nishi
- & Manuel Maldonado
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Article
| Open AccessA uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities
Protein corona is crucial for the safety and efficacy of nanomedicines, and the protein composition of the corona layer is typically analysed using liquid chromatography-mass spectrometry. Here the authors report that the use of a uniform database search provides an opportunity for taking measures in good practice and quality control in protein corona research using mass spectroscopy technique.
- Hassan Gharibi
- , Ali Akbar Ashkarran
- & Morteza Mahmoudi
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Article
| Open AccessMarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer
Identifying rare cell populations is key to understanding cancer progression and response to therapy. Here, authors introduce MarsGT, an end-to-end deep learning model for rare cell population identification from scMulti-omics data.
- Xiaoying Wang
- , Maoteng Duan
- & Qin Ma
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Article
| Open AccessTargeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats
Membrane-decorated nanomedicines often suffer from reduced efficacy caused by membrane artefacts during the coating process. Here the authors show that intracellularly gelated macrophages preserve membrane properties, stay stable under ambient temperature, and show therapeutic effects in murine models of joint and lung inflammation.
- Cheng Gao
- , Qingfu Wang
- & Ruibing Wang
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Article
| Open AccessMENDER: fast and scalable tissue structure identification in spatial omics data
Identifying tissue structure in large-scale spatial omics datasets from multiple slices is challenging. Here, authors present MENDER, an optimisation-free spatial clustering method that can scale to million-level spatial data, enabling efficient analysis of spatial cell atlases.
- Zhiyuan Yuan
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Article
| Open AccessA stapled lipopeptide platform for preventing and treating highly pathogenic viruses of pandemic potential
The ongoing emergence of highly pathogenic viruses that evade immune-based therapies or lack interventions mandates new approaches, especially for on-demand prophylaxis. Here the authors provide a stapled lipopeptide platform for the rapid development of viral fusion inhibitors to combat outbreaks.
- Gregory H. Bird
- , J. J. Patten
- & Loren D. Walensky
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Article
| Open AccessDe novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast
Xanthohumol is a prenylated flavonoid produced by hops and is an important flavor substance in beer. Here, the authors engineer brewing yeast for the de novo biosynthesis of xanthohumol from glucose by balancing the three parallel biosynthetic pathways.
- Shan Yang
- , Ruibing Chen
- & Yongjin J. Zhou
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Article
| Open AccessInhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy
A pro-tumorigenic role of iRhom1 has been described in several cancer types. Here the authors show that iRhom1 regulates sensitivity to chemotherapy and immune response, as well they report that CD44 targeting nanoparticle-mediated co-delivery of iRhom1 pre-siRNA promotes anti-tumor immune responses in preclinical cancer models.
- Zhangyi Luo
- , Yixian Huang
- & Song Li
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Article
| Open AccessAngiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts
The functional heterogeneity of autophagy in endothelial cells during angiogenesis remains incompletely understood. Here, the authors apply a 3D angiogenesis-on-a-chip coupled with single-cell RNA sequencing to find distinct autophagy functions in two different endothelial cell populations during angiogenic sprouting.
- Somin Lee
- , Hyunkyung Kim
- & Noo Li Jeon
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Article
| Open AccessAll-in-one porous membrane enables full protection in guided bone regeneration
Precise coupling of different or even contradictory material properties and biological characteristics is needed for tissue engineering but challenging. Here the authors report an all-in-one guided bone regeneration membrane that asymmetrically combines stiffness and flexibility, ingrowth barrier and ingrowth guiding, alongside anti-bacteria and cell-activation.
- Shuyi Wu
- , Shulu Luo
- & Yan Li
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Article
| Open AccessBionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function
Although artificial skins can facilitate the healing of damaged skin, the restoration of tactile functions remain a challenge. Here, Kang et al. report an artificial skin with an implantable tactile sensor that can simultaneously replace the tactile function by nerve stimulation and promote skin regeneration.
- Kyowon Kang
- , Seongryeol Ye
- & Youngmee Jung
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Article
| Open AccessCultured meat with enriched organoleptic properties by regulating cell differentiation
Achieving organoleptic properties of conventional meat is important for cultured meat production. Here, the authors demonstrate that the texture, flavor, and nutritional content of cultured meat can be significantly enhanced by regulating cell differentiation inside hydrogel scaffolds.
- Milae Lee
- , Sohyeon Park
- & Jinkee Hong
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Article
| Open AccessHigh throughput intracellular delivery by viscoelastic mechanoporation
Scalability of mechanoporation strategies for intracellular delivery remains challenging. Here, the authors demonstrate a microfluidic approach for delivering mRNA and CRISPR-Cas systems to over 250 million cells per minute.
- Derin Sevenler
- & Mehmet Toner
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Article
| Open AccessOptogenetic spatial patterning of cooperation in yeast populations
Microbial communities are the siege of complex metabolic interactions including cooperation and competition. Here, the authors report the utilization of optogenetics and spatial light-patterning to activate the expression of the invertase SUC2 at selected locations and selectively switch cooperation and competition roles of the yeast cells.
- Matthias Le Bec
- , Sylvain Pouzet
- & Pascal Hersen
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Article
| Open AccessHuman apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation
Airway organoids made in Matrigel are in basal-out orientation. Here, authors present apical-out nasal organoids using a biochemically defined hydrogel system, revealing that matrix metalloproteinases are required for normal epithelial development.
- Liyue Li
- , Linyi Jiao
- & Chunwei Li
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Article
| Open AccessMammalian cell growth characterisation by a non-invasive plate reader assay
Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here the authors develop a high throughput non-invasive method for tracking suspension and adhesion mammalian cell growth based on plate reader measures to characterize engineered cell lines.
- Alice Grob
- , Chiara Enrico Bena
- & Francesca Ceroni
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Article
| Open AccessTransient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells
Here the authors demonstrate that the frequency of HDR in human hematopoietic stem and progenitor cells is increased by the delivery of an inhibitor of 53BP1 as a recombinant peptide. This approach is applicable for a variety of therapeutically relevant loci in HSPCs as well in other primary human cell types.
- Ron Baik
- , M. Kyle Cromer
- & Matthew H. Porteus
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Article
| Open AccessACIDES: on-line monitoring of forward genetic screens for protein engineering
Screening mutated proteins is a versatile strategy in protein research, producing massive datasets when combined with NGS. Here, authors present ACIDES to estimate mutated protein fitness and aid protein engineering pipelines in a range of applications, including gene therapy.
- Takahiro Nemoto
- , Tommaso Ocari
- & Ulisse Ferrari
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Article
| Open AccessCharacterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease
Targeting gluten antigens presents a plausible therapy option for celiac disease. Here the authors generate and characterize a broadly neutralizing antibody recognizing more than 25 gluten peptide:HLA-DQ2.5 complexes, with structural analyses implicating its mode of interaction, and with mouse in vivo studies supporting its therapeutic feasibility.
- Yuu Okura
- , Yuri Ikawa-Teranishi
- & Tomoyuki Igawa
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Article
| Open AccessRedox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems
With redox-linked synthetic biology and electrobiofabrication, electronic information can be transmitted in a bidirectional manner between biology and electronics. Here the authors design an electrogenetic platform that allows real time electronic control of biological functions from proteins and gene circuits to cell consortia.
- Sally Wang
- , Chen-Yu Chen
- & William E. Bentley
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Article
| Open AccessBuilding synthetic chromosomes from natural DNA
Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.
- Alessandro L. V. Coradini
- , Christopher Ne Ville
- & Ian M. Ehrenreich
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Article
| Open AccessEngineering a synthetic energy-efficient formaldehyde assimilation cycle in Escherichia coli
One-carbon substrates are attractive feedstocks for circular bioeconomy. Here, the authors design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, demonstrate the activity of the core reactions in E. coli, and show its integration with pathway reactions existed in pentose phosphate pathway and glycolysis.
- Tong Wu
- , Paul A. Gómez-Coronado
- & Hai He
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Article
| Open AccessDeciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON
Deciphering the roles of gene regulation in cell fate decisions is crucial. Here, authors present CEFCON, a network-based framework that reveals cell-lineage-specific gene regulatory networks and identifies driver regulators controlling cell fate decisions from single-cell transcriptomics data.
- Peizhuo Wang
- , Xiao Wen
- & Jianyang Zeng
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Article
| Open AccessReconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica
Redox imbalance limits succinic acid (SA) biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, the authors engineering the aerobic yeast Yarrowia lipolytica for efficient SA production without pH control via coupling the oxidative and reductive TCA cycle for NADH regeneration in mitochondria.
- Zhiyong Cui
- , Yutao Zhong
- & Qingsheng Qi
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Article
| Open AccessOptimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors
Designing optogenetically functionalized G protein-coupled receptors (optoXRs) to mimic endogenous signaling in vivo is challenging. Here, the authors optimize the design of optoXRs by considering evolutionary conserved protein interactions, and they employ this approach in fruit flies.
- Fangmin Zhou
- , Alexandra-Madelaine Tichy
- & Peter Soba
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Article
| Open AccessHigh resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
- Amanda Janesick
- , Robert Shelansky
- & Sarah E. B. Taylor
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Review Article
| Open AccessCustomizing cellular signal processing by synthetic multi-level regulatory circuits
As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. In this review, the authors outline design strategies for the DNA, RNA, and protein-level circuits and the hybrid “multi-level” circuits.
- Yuanli Gao
- , Lei Wang
- & Baojun Wang
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Article
| Open AccessPathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
Clustering-based analysis has limited power in highly dynamic single-cell data, which is a common situation in tumour samples. Here, authors introduce GSDensity, enabling pathway-centric analysis for the direct integration of data with their domain knowledge.
- Qingnan Liang
- , Yuefan Huang
- & Ken Chen
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Article
| Open AccessIntranasal mask for protecting the respiratory tract against viral aerosols
The spread of many infectious diseases substantially relies on aerosol transmission to the respiratory tract. Here, the authors design an intranasal mask with the ability to intercept viral aerosols, entrap and inactivate virus, thus preventing respiratory tract infection.
- Xiaoming Hu
- , Shuang Wang
- & Wei Wei
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Article
| Open AccessSoft ferroelectret ultrasound receiver for targeted peripheral neuromodulation
Neurostimulators are often bulky and uncomfortable. Researchers report a wireless, leadless, and battery-free ultrasound receiver that wraps around the target peripheral nerve and allows precise modulation of organ function, providing a framework for future bioelectronic medicines
- Tong Li
- , Zhidong Wei
- & Zhang-Qi Feng
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Article
| Open AccessWhole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma
Current sequencing technologies can shed light on the stepwise progression of lung adenocarcinoma. Here, the authors characterize tumor progression in lung adenocarcinomas from an early stage using short and long read whole-genome sequencing, bulk and spatial transcriptomics, and epigenomics.
- Yasuhiko Haga
- , Yoshitaka Sakamoto
- & Ayako Suzuki
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Q&A
| Open AccessA conversation about cultivated meat
Summary: Cultivated or cultured meat is promising to revolutionize the food industry in the coming years to decades, helping to resolve concerns related to the environmental impact and ethical implications linked to conventional meat production. We talked to Dr. Sandhya Sriram, the Group CEO and Co-founder of Shiok Meats Pte. Ltd., Singapore; Prof. Shulamit Levenberg, the former Dean of the Biomedical Engineering Department at the Technion, current Director of the Technion Center for 3D Bioprinting and The Rina & Avner Schneur Center for Diabetes Research, as well as the Co-founder and Chief Scientific Adviser of Aleph Farms, Israel; and Dr. Timothy Olsen, Head of Cultured Meat in the Life Science business at Merck KGaA, Germany; about this relatively new and quickly developing sector. They explain what their teams are working on, including the biggest recent accomplishments, speak about the main challenges facing the field and how they can be resolved, and share their visions about the future of cultivated meat, aiming to provide more equitable and sustainable access to nutritious food for the growing world population.
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