Featured
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Article
| Open AccessSecretory GFP reconstitution labeling of neighboring cells interrogates cell–cell interactions in metastatic niches
Methodologies to study the mechanisms of cell–cell interactions in metastatic niches remain scarce. Here, the authors develop a secretory GFP reconstitution-based system to tag tissue-resident cells neighboring on cancer cells within the metastatic niche.
- Misa Minegishi
- , Takahiro Kuchimaru
- & Satoshi Nishimura
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Article
| Open AccessMetabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines
Extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. Here, the authors report a universal metabolic tagging technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV-based cancer vaccines.
- Rimsha Bhatta
- , Joonsu Han
- & Hua Wang
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Article
| Open AccessEngineering artificial photosynthesis based on rhodopsin for CO2 fixation
Microbial rhodopsins are major contributors to global light harvesting on Earth, but their role in carbon fixation is unclear. Here, the authors construct an artificial photosynthesis system by combining rhodopsin with an extracellular electron uptake mechanism for photoelectrosynthetic CO2 fixation in Ralstonia eutropha.
- Weiming Tu
- , Jiabao Xu
- & Wei E. Huang
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Article
| Open AccessDynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry
Off-target toxicity of antisense oligonucleotides (ASOs) poses a challenge for their clinical use. Here, authors develop a toehold-bearing ASO architecture that mitigates a broad spectrum of off-target interactions, significantly enhancing the safety profile of ASO drugs.
- Chisato Terada
- , Kaho Oh
- & Tsuyoshi Yamamoto
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Article
| Open AccessFully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation
Electrical stimulation of the neuromuscular system holds promise for therapeutic biomedical applications, but is currently restricted by power. Here, the authors introduce fully implantable resonator-based designs achieving ±20 V compliance and >300 mW output, enabling multichannel, biphasic, current-controlled operation to evoke functional gate patterns for 6-weeks in freely behaving rats.
- Alex Burton
- , Zhong Wang
- & Philipp Gutruf
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Article
| Open AccessEngineered immunogens to elicit antibodies against conserved coronavirus epitopes
A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.
- A. Brenda Kapingidza
- , Daniel J. Marston
- & Mihai L. Azoitei
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Article
| Open AccessXylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
It’s challenging to produce natural products using single strains of engineered microbes fed by renewable carbon sources. Here, the authors assemble a microbial consortium consisting of engineered S. stipitis and S. cerevisiae for streamlined production of (S)-norcoclaurine from glucose and xylose simultaneously.
- Meirong Gao
- , Yuxin Zhao
- & Zengyi Shao
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Article
| Open AccessInterrogating ligand-receptor interactions using highly sensitive cellular biosensors
The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.
- Maximilian A. Funk
- , Judith Leitner
- & Peter Steinberger
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Article
| Open AccessLocal H2 release remodels senescence microenvironment for improved repair of injured bone
Senescence microenvironment inhibits tissue repair in elderly individuals. Here, the authors demonstrate that local H2 supply has anti-inflammation and anti-senescence effects, and develop a H2-releasing scaffold to enhance aging bone defect repair.
- Shengqiang Chen
- , Yuanman Yu
- & Qianjun He
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Article
| Open AccessDetection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer
Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.
- Arthur Dondi
- , Ulrike Lischetti
- & Niko Beerenwinkel
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Article
| Open AccessA simeprevir-inducible molecular switch for the control of cell and gene therapies
Chemical inducer of dimerization (CID) modules can be used to effectively control biological processes; however, CID modules have been explored primarily in engineering cells for in vitro applications using inducers that have limited clinical utility. Here, the authors identify a CID module with favorable properties to enable rapid translation from in vitro applications to potential use in humans.
- Stacey E. Chin
- , Christina Schindler
- & Natalie J. Tigue
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Article
| Open AccessDiscovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery
Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.
- Jinzhong Tian
- , Wangshuying Deng
- & Yang Gu
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Article
| Open AccessUltra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration
Achieving successful in vivo cartilage regeneration remains challenging. Here they present a cell-free, multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin with ultra-durable mechanical properties and stage-dependent drug release behavior to promote cartilage regeneration.
- Yuxuan Yang
- , Xiaodan Zhao
- & Xuesi Chen
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Article
| Open AccessA fully integrated, standalone stretchable device platform with in-sensor adaptive machine learning for rehabilitation
Methods for the wireless, continuous monitoring and analysis of activities directly from the throat skin have not been developed. Here, the authors present a stretchable device platform that provides wireless measurements and machine learning-based analysis of vibrations and muscle electrical activities from the throat.
- Hongcheng Xu
- , Weihao Zheng
- & Libo Gao
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Article
| Open AccessThe oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii
One carbon compounds such as CO2, methanol and formate are cost-effective and environmentally friendly microbial feedstocks for biomanufacturing. Here, the authors report the oxygen tolerant reductive glycine pathway in Komagataella phaffii can co-assimilate CO2, methanol and formate.
- Bernd M. Mitic
- , Christina Troyer
- & Diethard Mattanovich
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Article
| Open AccessOcclusive membranes for guided regeneration of inflamed tissue defects
Symbiosis should be maintained during the oral regeneration period. Herein, authors develop an occlusive membrane that induces symbiosis, thereby improving the performance of guided bone generation therapy.
- Woojin Choi
- , Utkarsh Mangal
- & Jinkee Hong
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Article
| Open AccessIn vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor
Mutations in mitochondrial DNA (mtDNA) play critical roles in human diseases. Here, the authors describe an integrated Cas12a sensor for sensing mtDNA mutations in vivo, showing potential for diagnostic and therapeutic purposes.
- Yanan Li
- , Yonghua Wu
- & Kaixiang Zhang
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Article
| Open AccessNanoparticles exhibiting virus-mimic surface topology for enhanced oral delivery
The oral delivery of nano-drug delivery systems (Nano-DDS) remains challenging. Here the authors construct core–shell mesoporous silica nanoparticles with virus-like nanospikes and demonstrate the versatility of these nanoparticles as Nano-DDS to achieve efficient oral drug delivery by mimicking structural feature, chiral recognition, and gene encapsulation of viruses.
- Zhentao Sang
- , Lu Xu
- & Heran Li
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Article
| Open Access3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry
Geometrical complexities of blood vessels alter biophysical behaviors of circulating tumor cells, influencing cancer metastasis. Here, the authors develop a 3D bioprinted in vitro brain blood vessel-on-a-chip to investigate continuities between vascular geometry and metastatic cancer development.
- Wonbin Park
- , Jae-Seong Lee
- & Dong-Woo Cho
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Article
| Open AccessBiofilm microenvironment triggered self-enhancing photodynamic immunomodulatory microneedle for diabetic wound therapy
The treatment of diabetic wounds tends to be hindered by complex wound environments, and the critical role of the microenvironment in the chronic diabetic wounds has not been explored for therapeutic development. Here, the authors develop a wound microenvironment-responsive microneedle bandage to achieve self-enhanced, catabolic and dynamic therapy of chronic wounds.
- Li Yang
- , Dan Zhang
- & Xiaowei Zeng
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Article
| Open AccessSPACEL: deep learning-based characterization of spatial transcriptome architectures
Spatial transcriptomics (ST) technologies detect transcript distribution in space. Here, authors present a deep learning based method SPACEL for cell type deconvolution, spatial domain identification and 3D alignment, showcasing it as a valuable toolkit for ST data analysis
- Hao Xu
- , Shuyan Wang
- & Kun Qu
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Article
| Open AccessFour-dimensional hydrogel dressing adaptable to the urethral microenvironment for scarless urethral reconstruction
Urethral repair can be carried out using hydrogels, but the harsh microenvironment hinders the repair. Here, the authors report the development of a 4D hydrogel dressing that can provide an early-vascularised and later-antifibrogenic microenvironment to assist in scarless reconstruction.
- Yujie Hua
- , Kai Wang
- & Kaile Zhang
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Article
| Open AccessA semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening
Cell-based phenotypic assays link in vitro discovery to disease pathology. Here, the authors report a semiconductor-based microplate platform to perform high-throughput, high-dimensional “electrical imaging” for label-free assessment of live cell morphology and function.
- Shalaka Chitale
- , Wenxuan Wu
- & Jeffrey Abbott
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Article
| Open AccessCis-trans isomerization of peptoid residues in the collagen triple-helix
The cis-peptide bond is rare in natural proteins and its impact on protein folding is elusive. Here the authors break the conventional understanding that cis-amide-favoring residues destabilize proteins, elucidate the principles of peptoid cis-trans isomerization in collagen folding, and showcase the use of cis-amide-favoring residues in building programmable and functional peptidomimetics.
- Rongmao Qiu
- , Xiaojing Li
- & Yang Li
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Article
| Open AccessCRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus
Culex mosquitoes are carriers of major diseases like West Nile virus and are a public health concern. Here the authors present a CRISPR-Cas9 gene drive as a control technology in the Culex quinquefasciatus mosquito species.
- Tim Harvey-Samuel
- , Xuechun Feng
- & Valentino M. Gantz
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Article
| Open AccessAsymmetric CRISPR enabling cascade signal amplification for nucleic acid detection by competitive crRNA
New strategies are being developed to simplify CRISPR-based nucleic acid detection. By investigating the competitive reaction between a full-sized crRNA and split crRNA for CRISPR-Cas12a, the authors develop an asymmetric CRISPR assay for amplification-free, cascade signal amplification detection of nucleic acids.
- Jeong Moon
- & Changchun Liu
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Article
| Open AccessDiurnal switches in diazotrophic lifestyle increase nitrogen contribution to cereals
Engineering ammonium excretion diazotrophs suffers from severe penalties to the bacteria. Here, the authors utilize a thermo-sensitive glutamine synthetase-based regulatory switch that permits diurnal changes in diazotrophic lifestyle, coincident with seasonal temperatures for cereal cultivation.
- Yuqian Tang
- , Debin Qin
- & Yi-Ping Wang
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Article
| Open AccessHigh-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq
Understanding T cell behaviour in cancers is vital for improving immunotherapies. Here, the authors present spatially resolved T cell receptor sequencing (SPTCR-seq), a technology that annotates T cell receptors within the tumour ecosystem.
- Jasim Kada Benotmane
- , Jan Kueckelhaus
- & Dieter Henrik Heiland
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Article
| Open AccessPolyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis
Verticillum wilt is an important cotton disease caused by fungal pathogen Verticillium dahiae. Here, the authors assemble the genomes of defoliating and non-defoliating isolates of the pathogen, identify virulence gene SP3, and develop a disease control strategy using polyethyleneimine-coated MXene quantum dots.
- Ping Qiu
- , Jiayue Li
- & Longfu Zhu
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Article
| Open AccessPan-genome analysis of 13 Malus accessions reveals structural and sequence variations associated with fruit traits
A pan-genome can reduce bias in genetic diversity analysis inherent in using a single reference genome. Here, the authors assemble genomes of 10 diverse apple accessions, conduct pan-genome analysis together with three existing genomes, and reveal the role of mitogen-activated protein kinase homolog MMK2 in fruit coloration.
- Ting Wang
- , Shiyao Duan
- & Ting Wu
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Article
| Open AccessImaging cellular forces with photonic crystals
Current techniques for visualizing cell generated forces suffer from throughput limitations. Here, Gu et al. introduced photonic crystal cellular force microscopy, inspired by chameleons, enabling visualization and quantification of vertically directed cell forces, well-suited for drug screening.
- Qiwei Li
- , Zaozao Chen
- & Zhongze Gu
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Article
| Open AccessSingle amino acid change alters specificity of the multi-allelic wheat stem rust resistance locus SR9
Among all wheat rust resistance genes, SR9 has the largest number of alleles. Here, the authors use gene cloning, complementation and comparative genetics to resolve the relationship among Sr9 alleles, confirm their allelic identities, and show that a single amino acid change leads to resistance to Ug99.
- Jianping Zhang
- , Jayaveeramuthu Nirmala
- & Evans Lagudah
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Article
| Open AccessEnhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury
Treatment alternatives are not available for a significant portion of critical limb ischemia patients. Here, the authors show a strategy to engineer mesenchymal stem cells-derived extracellular vesicles to induce revascularization in mice.
- Ling Guo
- , Qiang Yang
- & Min Feng
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Article
| Open AccessEmergence of task-related spatiotemporal population dynamics in transplanted neurons
Cell therapy is a promising treatment for brain injury, but it is unclear if transplanted neurons demonstrate population dynamics. By monitoring transplanted neurons in injured mice, here the authors show the emergence of dynamics resembling intact networks.
- Harman Ghuman
- , Kyungsoo Kim
- & Karunesh Ganguly
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Article
| Open AccessDiatomic iron nanozyme with lipoxidase-like activity for efficient inactivation of enveloped virus
Enveloped viruses encased within a lipid bilayer membrane are highly contagious and cause diseases like influenza and COVID-19, so strategies for their prevention and inactivation are needed. Here, the authors develop a diatomic iron nanozyme with lipoxidase-like activity for the inactivation of enveloped viruses, where the diatomic iron sites destroy the viral envelope via lipid peroxidation.
- Beibei Li
- , Ruonan Ma
- & Yadong Li
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Article
| Open AccessAn on-demand bioresorbable neurostimulator
Despite promising advantages, bioresorbable electronics face practical limitations due to unpredictable device lifetimes. Here, the authors introduce an on-demand bioresorbable neurostimulator powered by biosafe ultrasound to treat peripheral nerve injury and neuropathies.
- Dong-Min Lee
- , Minki Kang
- & Sang-Woo Kim
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Article
| Open AccessLung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models
Roughly 10% of Cystic Fibrosis (CF) patients still have no effective medicine to take. Lung Selective Organ Targeting (SORT) Lipid Nanoparticles can efficiently deliver Cas9 mRNA, sgRNA, and donor ssDNA templates for precise homology-directed repair-mediated gene correction in ex vivo and in vivo CF models.
- Tuo Wei
- , Yehui Sun
- & Daniel J. Siegwart
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Article
| Open AccessEngineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds
Sufficient supply of sulfonate group donor is critical to biomanufacturing of the sulfate containing compounds. Here, the authors engineer two sulfonate group donor regeneration systems, including 3'-phosphoadenosine-5'-phosphosulfate and the newly discovered 5'-phosphosulfate, to boost biosynthesis of sulfated compounds.
- Ruirui Xu
- , Weijao Zhang
- & Zhen Kang
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Article
| Open AccessA statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples
Pseudotime analysis is prevalent in single-cell RNA-seq, but it remains challenging to perform it across multiple samples and experimental conditions. Here, the authors develop Lamian, a computational framework for multi-sample pseudotime analysis that adjusts for biological and technical variation to detect gene program changes along cell trajectories and across conditions.
- Wenpin Hou
- , Zhicheng Ji
- & Hongkai Ji
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Article
| Open AccessNULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
Unlocking the blood proteome requires exquisite sensitivity and multiplexing to detect low and high abundance proteins simultaneously. Here the authors describe a 200-plex immunoassay with attomolar sensitivity to detect important low abundance proteins in inflammatory diseases and COVID-19.
- Wei Feng
- , Joanne C. Beer
- & Xiao-Jun Ma
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Article
| Open AccessSphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy
Epacadostat is a selective IDO1 inhibitor shown to promote anti-tumor immune responses in preclinical models, however it has failed in a Phase III clinical trial for treating metastatic melanoma. Here the authors design a sphingomyelin-derived nanovesicle system for epacadostat delivery with improved pharmacokinetics and anti-tumor activity when combined with a PD-1 inhibitor in melanoma preclinical models.
- Zhiren Wang
- , Wenpan Li
- & Jianqin Lu
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Article
| Open AccessAdoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection
There is increased demand for effective, broad-spectrum treatment options against severe, multi-drug resistant bacterial infections. Here, Wang et al describe an effective photodynamic therapy based on the adoptive transfer of macrophages loaded with a lysosomal photosensitiser.
- Zehui Wang
- , Anhua Wu
- & Yi Xiao
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Article
| Open AccessElectrocatalytic on-site oxygenation for transplanted cell-based-therapies
Oxygen is the most limiting factor in cell transplantation. Here, the authors present an on-site oxygen production platform for implantable cell therapeutics via electrocatalytic water electrolysis, demonstrating the maintenance of high cell loading in hypoxic incubation and a rat model.
- Inkyu Lee
- , Abhijith Surendran
- & Tzahi Cohen-Karni
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Article
| Open AccessCoordinated regulation of the entry and exit steps of aromatic amino acid biosynthesis supports the dual lignin pathway in grasses
The study by El-Azaz et al. uncovers how grasses fine-tune tyrosine and phenylalanine production to support their unique dual entry pathway to lignin and phenylpropanoids. The findings help improve sustainable production of aromatic chemicals in crops.
- Jorge El-Azaz
- , Bethany Moore
- & Hiroshi A. Maeda
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Article
| Open AccessRational design of microRNA-responsive switch for programmable translational control in mammalian cells
Artificial regulation of translation by intracellular RNAs has many potential applications. Here, authors design a platform capable of miRNA-triggered upregulation or downregulation using a single RNA construct, and demonstrate its use in constructing logic gates and cell-type classifiers.
- Hui Ning
- , Gan Liu
- & Zhen Xie
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Article
| Open AccessCell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides
Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.
- Amir Pandi
- , David Adam
- & Tobias J. Erb
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Article
| Open AccessPathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke
Reperfusion is a main strategy for restoring blood supply after ischemic stroke, but it induces neuroinflammation that undergoes dynamic progression, hindering the treatment of ischemic stroke. Here, the authors report a pathogenesis-adaptive nanosystem for sequential and on-demand regulation of reperfusion-induced dynamic neuroinflammation for ischemic stroke therapy.
- Di Wu
- , Jing Zhou
- & Zhong Chen
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Article
| Open AccessBioinspired porous three-coordinated single-atom Fe nanozyme with oxidase-like activity for tumor visual identification via glutathione
It is needed yet difficult to achieve a strategy for synthesizing single-atom nanozymes that integrate atomic metal dispersion, elevated mass transport and tailorable coordination environment. Here, the authors address this issue by developing a biomimetic synthetic strategy and demonstrate the application of the resultant single-atom Fe nanozymes for tumor visual identification.
- Da Chen
- , Zhaoming Xia
- & Yongquan Qu
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Article
| Open AccessA TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation
Overexpression of human antigen R (HuR) correlates with high grade tumours and poor patient prognosis. Here, the authors engineer a TRIM21 biological PROTAC to demonstrate the benefit of a targeted protein degradation approach to deplete HuR, resulting in tumour growth inhibition in pre-clinical cancer models by altering the HuR-regulated proteome.
- Alice Fletcher
- , Dean Clift
- & James Hunt
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