GABAergic signaling between enteric neurons and intestinal smooth muscle promotes innate immunity and gut defense in Caenorhabditis elegans.

The nervous system is critical for intestinal homeostasis and function, but questions remain regarding its impact on gut immune defense. By screening the major neurotransmitters of C. elegans, we found that γ-aminobutyric acid (GABA) deficiency enhanced susceptibility to pathogenic Pseudomonas aeruginosa PA14 infection. GABAergic signaling between enteric neurons and intestinal smooth muscle promoted gut defense in a PMK-1/p38-dependent, but IIS/DAF-16- and DBL-1/TGF-ß-independent, pathway. Transcriptomic profiling revealed that the neuropeptide, FLP-6, acted downstream of enteric GABAergic signaling. Further data determined that FLP-6 was expressed and secreted by intestinal smooth muscle cells and functioned as a paracrine molecule on the intestinal epithelium. FLP-6 suppressed the transcription factors ZIP-10 and KLF-1 that worked in parallel and converged to the PMK-1/p38 pathway in the intestinal epithelia for innate immunity and gut defense. Collectively, these findings uncover an enteric neuron-muscle-epithelium axis that may be evolutionarily conserved in higher organisms.

The Drosophila NPY-like system protects against chronic stress-induced learning deficit by preventing the disruption of autophagic flux.

Chronic stress may induce learning and memory deficits that are associated with a depression-like state in Drosophila melanogaster. The molecular and neural mechanisms underlying the etiology of chronic stress-induced learning deficit (CSLD) remain elusive. Here, we show that the autophagy-lysosomal pathway, a conserved cellular signaling mechanism, is associated with chronic stress in Drosophila, as indicated by time-series transcriptome profiling. Our findings demonstrate that chronic stress induces the disruption of autophagic flux, and chronic disruption of autophagic flux could lead to a learning deficit. Remarkably, preventing the disruption of autophagic flux by up-regulating the basal autophagy level is sufficient to protect against CSLD. Consistent with the essential role of the dopaminergic system in modulating susceptibility to CSLD, dopamine neuronal activity is also indispensable for chronic stress to induce the disruption of autophagic flux. By screening knockout mutants, we found that neuropeptide F, the Drosophila homolog of neuropeptide Y, is necessary for normal autophagic flux and promotes resilience to CSLD. Moreover, neuropeptide F signaling during chronic stress treatment promotes resilience to CSLD by preventing the disruption of autophagic flux. Importantly, neuropeptide F receptor activity in dopamine neurons also promotes resilience to CSLD. Together, our data elucidate a mechanism by which stress-induced excessive dopaminergic activity precipitates the disruption of autophagic flux, and chronic disruption of autophagic flux leads to CSLD, while inhibitory neuropeptide F signaling to dopamine neurons promotes resilience to CSLD by preventing the disruption of autophagic flux.

Sls1 and Mtf2 mediate the assembly of the Mrh5C complex required for activation of cox1 mRNA translation.

Mitochondrial translation depends on mRNA-specific activators. In Schizosaccharomyces pombe, DEAD-box protein Mrh5, pentatricopeptide repeat (PPR) protein Ppr4, Mtf2, and Sls1 form a stable complex (designated Mrh5C) required for translation of mitochondrial DNA (mtDNA)-encoded cox1 mRNA, the largest subunit of the cytochrome c oxidase complex. However, how Mrh5C is formed and what role Mrh5C plays in cox1 mRNA translation have not been reported. To address these questions, we investigated the role of individual Mrh5C subunits in the assembly and function of Mrh5C. Our results revealed that Mtf2 and Sls1 form a subcomplex that serves as a scaffold to bring Mrh5 and Ppr4 together. Mrh5C binds to the small subunit of the mitoribosome (mtSSU), but each subunit could not bind to the mtSSU independently. Importantly, Mrh5C is required for the association of cox1 mRNA with the mtSSU. Finally, we investigated the importance of the signature DEAD-box in Mrh5. We found that the DEAD-box of Mrh5 is required for the association of Mrh5C and cox1 mRNA with the mtSSU. Unexpectedly, this motif is also required for the interaction of Mrh5 with other Mrh5C subunits. Altogether, our results suggest that Mrh5 and Ppr4 cooperate in activating the translation of cox1 mRNA. Our results also suggest that Mrh5C activates the translation of cox1 mRNA by promoting the recruitment of cox1 mRNA to the mtSSU.

VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.

Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.

Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple-negative breast cancer progression.

TGF-ß signaling pathway plays a key role in breast cancer metastasis. Recent studies suggest that TGF-ß regulates tumor progression and invasion not only via transcriptional regulation, but also via translational regulation. Using both bioinformatics and experimental tools, we identified a micropeptide CIP2A-BP encoded by LINC00665, whose translation was downregulated by TGF-ß in breast cancer cell lines. Using TNBC cell lines, we showed that TGF-ß-activated Smad signaling pathway induced the expression of translation inhibitory protein 4E-BP1, which inhibited eukaryote translation initiation factor elF4E, leading to reduced translation of CIP2A-BP from LINC00665. CIP2A-BP directly binds tumor oncogene CIP2A to replace PP2A's B56γ subunit, thus releasing PP2A activity, which inhibits PI3K/AKT/NFκB pathway, resulting in decreased expression levels of MMP-2, MMP-9, and Snail. Downregulation of CIP2A-BP in TNBC patients was significantly associated with metastasis and poor overall survival. In the MMTV-PyMT model, either introducing CIP2A-BP gene or direct injection of CIP2A-BP micropeptide significantly reduced lung metastases and improved overall survival. In conclusion, we provide evidence that CIP2A-BP is both a prognostic marker and a novel therapeutic target for TNBC.

Tailoring the Hydrophobic Interface of Core-Shell HKUST-1@Cu2O Nanocomposites for Efficiently Selective CO2 Electroreduction.

The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon-neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory-designed catalyst HKUST-1@Cu2O/PTFE-1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (-1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbon（C2+） product. In this work, a promising and effective strategy is presented to configure MOF-based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.

vsRNAfinder: a novel method for identifying high-confidence viral small RNAs from small RNA-Seq data.

Virus-encoded small RNAs (vsRNA) have been reported to play an important role in viral infection. Unfortunately, there is still a lack of an effective method for vsRNA identification. Herein, we presented vsRNAfinder, a de novo method for identifying high-confidence vsRNAs from small RNA-Seq (sRNA-Seq) data based on peak calling and Poisson distribution and is publicly available at https://github.com/ZenaCai/vsRNAfinder. vsRNAfinder outperformed two widely used methods namely miRDeep2 and ShortStack in identifying viral miRNAs with a significantly improved sensitivity. It can also be used to identify sRNAs in animals and plants with similar performance to miRDeep2 and ShortStack. vsRNAfinder would greatly facilitate effective identification of vsRNAs from sRNA-Seq data.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

Biosynthesis of Bt-Ag2O nanoparticles using Bacillus thuringiensis and their pesticidal and antimicrobial activities.

Nanosilver oxide exhibits strong antibacterial and photocatalytic properties and has shown great application potential in food packaging, biochemical fields, and other fields involving diseases and pest control. In this study, Ag2O nanoparticles were synthesized using Bacillus thuringiensis (Bt-Ag2O NPs). The physicochemical characteristics of the Bt-Ag2O NPs were analyzed by UV‒vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), inductively coupled plasma emission spectrometry (ICP), high-resolution transmission electron microscopy (HR-TEM), and zeta potential. The phis-chemical characterization revealed that the Bt-Ag2O NPs are in spherical shape with the small particle size (18.24 nm), high crystallinity, well dispersity, and stability. The biopesticidal and antifungal effects of Bt-Ag2O NPs were tested against Tribolium castaneum, Aspergillus flavus, and Penicillium chrysogenum. The survival, growth, and reproduction of tested pests and molds were significantly inhibited by Bt-Ag2O NPs in a dose-dependent manner. Bt-Ag2O NPs showed higher pesticidal activities against T. castaneum than Bt and commercial Ag2O NPs. The LC50 values of Bt, Ag2O NPs, and Bt-Ag2O NPs were 0.139%, 0.072%, and 0.06% on day 14, respectively. The Bt-Ag2O NPs also showed well antifungal activities against A. flavus and P. chrysogenum, while it resulted a small inhibition zone than commercial Ag2O NPs did. In addition, A. flavus showed much more sensitive to Bt-Ag2O NP treatments, compared to P. chrysogenum. Our results revealed that Bt-Ag2O NPs synthesized using B. thuringiensis could act as pesticides and antifungal agents in stored-product fields. KEY POINTS: • Bt-Ag2O NPs could be synthesized using Bacillus thuringiensis (Bt). • The NPs showed a high degree of crystallinity, spherical shape, and small particle size. • The NPs also showed excellent insecticidal and antifungal activity.

A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway.

Autophagy plays a crucial role in the development and progression of ischemic acute kidney injury (AKI). However, the function and mechanism of circular RNAs (circRNAs) in the regulation of autophagy in ischemic AKI remain unexplored. Herein, we find that circ-ZNF609, originating from the ZNF609 locus, is highly expressed in the kidney after ischemia/reperfusion injury, and urinary circ-ZNF609 is a moderate predictor for AKI in heart disease patients. Overexpression of circ-ZNF609 can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis while inhibiting proliferation in HK-2 cells, which is blocked by silencing circ-ZNF609. Mechanistically, circ-ZNF609 encodes a functional protein consisting of 250 amino acids (aa), termed ZNF609-250aa, the overexpression of which can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis in HK-2 cells in vitro and in AKI kidneys in vivo. The blockade of AKT and mTOR signaling with pharmacological inhibitors is capable of reversing ZNF609-250aa-induced autophagy flux impairment and cell apoptosis in HK-2 cells. The present study demonstrates that highly expressed circ-ZNF609-encoded ZNF609-250aa induces cell apoptosis and AKI by impairing the autophagy flux via an AKT/mTOR-dependent mechanism. These findings imply that targeting circ-ZNF609 may be a novel therapy for ischemic AKI.

SCH772984 ameliorates lipopolysaccharide-induced hypoglycemia in mice through reversing MEK/ERK/Foxo1-mediated gluconeogenesis suppression.

Lipopolysaccharide (LPS) results in a lethal hypoglycemic response. However, the main molecular mechanism involved in LPS-induced glucose metabolism disorder is poorly understood. This study intends to investigate the signaling pathways involved in LPS-induced hypoglycemia and potential efficacy of extracellular signal-regulated kinase (ERK) inhibitor SCH772984. The effects of LPS and SCH772984 on gluconeogenesis, glucose absorption, and glycogenolysis were evaluated by pyruvate tolerance test, oral glucose tolerance test, and glucagon test, respectively. After a single intraperitoneal injection of 0.5 mg/kg LPS, the mice's blood glucose levels and gluconeogenesis ability were significantly lower than that of control group. Besides, mRNA and protein expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased significantly after LPS treatment. LPS induced the phosphorylation of ERK1/2, MEK1/2 (mitogen-activated protein kinase), and Foxo1 while inhibited Foxo1 expression in the nucleus, indicating an important role of the MEK/ERK/Foxo1 signaling in the inhibition of gluconeogenesis by LPS. Furthermore, SCH772984 elevated blood glucose, increased the G6Pase and PEPCK expression, and inhibited pERK1/2 and pFoxo1 expression in LPS-induced mice. In summary, LPS inhibited gluconeogenesis and induced hypoglycemia through the MEK/ERK/Foxo1 signal pathway, and ERK inhibitor could effectively reverse decreased blood glucose in mice with LPS treatment. These findings provide a novel therapeutic target for LPS-induced hypoglycemia.

Multi-Omic Analysis Reveals Genetic Determinants and Therapeutic Targets of Chronic Kidney Disease and Kidney Function.

Chronic kidney disease (CKD) presents a significant global health challenge, characterized by complex pathophysiology. This study utilized a multi-omic approach, integrating genomic data from the CKDGen consortium alongside transcriptomic, metabolomic, and proteomic data to elucidate the genetic underpinnings and identify therapeutic targets for CKD and kidney function. We employed a range of analytical methods including cross-tissue transcriptome-wide association studies (TWASs), Mendelian randomization (MR), summary-based MR (SMR), and molecular docking. These analyses collectively identified 146 cross-tissue genetic associations with CKD and kidney function. Key Golgi apparatus-related genes (GARGs) and 41 potential drug targets were highlighted, with MAP3K11 emerging as a significant gene from the TWAS and MR data, underscoring its potential as a therapeutic target. Capsaicin displayed promising drug-target interactions in molecular docking analyses. Additionally, metabolome- and proteome-wide MR (PWMR) analyses revealed 33 unique metabolites and critical inflammatory proteins such as FGF5 that are significantly linked to and colocalized with CKD and kidney function. These insights deepen our understanding of CKD pathogenesis and highlight novel targets for treatment and prevention.

Technological progress and coupling renewables enable substantial environmental and economic benefits from coal-to-olefins.

China's growing demand for bulk chemicals and concerns regarding energy security are scaling up coal-to-olefins (CTO) production. Three generations of independent dimethyl ether/methanol-to-olefins technologies have been successively launched with greatly improved production efficiencies. However, to date, widespread concerns regarding the intensive environmental impacts and potential economic risks have not been addressed in the context of this industrialization. Here we show that, through the technological progress from the first to the third generation, life cycle energy consumption, water consumption, and carbon emissions can be reduced to 119.5 GJ/t, 27.6 t/t, and 9.1 t CO2-eq/t, respectively, and human health damage, ecosystem quality damage, and resource scarcity impacts can be decreased by 40.5 %, 50.1 %, and 16.4 %, respectively. This is accompanied by an excellent performance in terms of production cost, net present value, and internal return rate at 792.5 USD/t, 173.4 USD/t, and 19.4 %, respectively. Substantial environmental and economic benefits can be gained by coupling renewables in the form of using green hydrogen from solar and wind power to synthesize methanol. Particularly, life cycle carbon emissions and resource scarcity impacts are reduced by 23.4 % and 22.4 %, respectively, exceeding the reduction in technological progress. However, coupling renewables increases the life cycle energy consumption to 154.5 GJ/t, counteracting the benefits of technological progress. Our results highlight the importance of technological progress and coupled renewables for enhancing the sustainability of the CTO industry.

Redox Molecular Junction Metal-Covalent Organic Frameworks for Light-assisted CO2 Energy Storage.

Visible-light sensitive and bi-functionally favored CO2 reduction (CRR)/evolution (CER) photocathode catalysts that can get rid of the utilization of ultraviolet light and improve sluggish kinetics is demanded to conquer the current technique-barrier of traditional Li-CO2 battery. Here, a kind of redox molecular junction sp2c metal-covalent organic framework (i.e. Cu3-BTDE-COF) has been prepared through the connection between Cu3 and BTDE and can serve as efficient photocathode catalyst in light-assisted Li-CO2 battery. Cu3-BTDE-COF with redox-ability, visible-light-adsorption region, electron-hole separation ability and endows the photocathode with excellent round-trip efficiency (95.2 %) and an ultralow voltage hysteresis (0.18 V), outperforming the Schiff base COFs (i.e. Cu3-BTDA-COF and Cu3-DT-COF) and majority of the reported photocathode catalysts. Combined theoretical calculations with characterizations, Cu3-BTDE-COF with the integration of Cu3 centers, thiazole and cyano groups possess strong CO2 adsorption/activation and Li+ interaction/diffusion ability to boost the CRR/CER kinetics and related battery property.

Function and Evolution of Upstream ORFs in Eukaryotes.

There is growing interest in the role of translational regulation in cellular homeostasis during organismal development. Translation initiation is the rate-limiting step in mRNA translation and is central to translational regulation. Upstream open reading frames (uORFs) are regulatory elements that are prevalent in eukaryotic mRNAs. uORFs modulate the translation initiation rate of downstream coding sequences (CDSs) by sequestering ribosomes. Over the past several years, genome-wide studies have revealed the widespread regulatory functions of uORFs in different species in different biological contexts. Here, we review the current understanding of uORF-mediated translational regulation from the perspective of functional and evolutionary genomics and address remaining gaps that deserve further study.

Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation.

O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanism by which OGT regulates gene transcription remains elusive. Using proximity labeling-based mass spectrometry, here, we searched for functional partners of OGT and identified interacting protein Dot1L, a conserved and unique histone methyltransferase known to mediate histone H3 Lys79 methylation, which is required for gene transcription, DNA damage repair, cell proliferation, and embryo development. Although this specific interaction with OGT does not regulate the enzymatic activity of Dot1L, we show that it does facilitate OGT-dependent histone O-GlcNAcylation. Moreover, we demonstrate that OGT associates with Dot1L at transcription start sites and that depleting Dot1L decreases OGT associated with chromatin globally. Notably, we also show that downregulation of Dot1L reduces the levels of histone H2B S112 O-GlcNAcylation and histone H2B K120 ubiquitination in vivo, which are associated with gene transcription regulation. Taken together, these results reveal that O-GlcNAcylation of chromatin is dependent on Dot1L.

Metabolomic interplay between gut microbiome and plasma metabolome in cardiac surgery-associated acute kidney injury.

RATIONALE: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication of cardiac surgery, which may be associated with a great risk of developing chronic kidney disease and mortality. This study aimed to investigate the possible links between gut microbiota metabolism and CSA-AKI. METHODS: A prospective cohort of patients who underwent cardiac surgery was continuously recruited, who were further divided into CSA-AKI group and Non-AKI group based on clinical outcomes. Their faecal and plasma samples were collected before surgery and were separately analysed by nontargeted and targeted metabolomics. The differential metabolites related to CSA-AKI were screened out using statistical methods, and altered metabolic pathways were determined by examining the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Nearly 1000 faecal metabolites were detected through high-resolution mass spectrometry (MS) and bioinformatics at high and mid confidence levels, and 49 differential metabolites at high confidence level may perform essential biological functions and provide potential diagnostic indicators. Compared with the Non-AKI group, the patients in the CSA-AKI group displayed dramatic changes in gut microbiota metabolism, including amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism and ATP-binding cassette (ABC) transporters. Meanwhile, 188 plasma metabolites were identified and quantified by tandem MS, and 34 differential plasma metabolites were screened out between the two groups using univariate statistical analysis. These differential plasma metabolites were primarily enriched in the following metabolic pathways: sulphur metabolism, amino acid biosynthesis, tryptophan metabolism and ABC transporters. Furthermore, the content of indole metabolites in the faecal and plasma samples of the CSA-AKI group was higher than that of the Non-AKI group. CONCLUSIONS: Patients with CSA-AKI may have dysbiosis of their intestinal microbiota and metabolic abnormalities in their gut system before cardiac surgery. Thus, some metabolites and related metabolic pathways may be potential biomarkers and new therapeutic targets for the disease.

Antagonistic effects of mitochondrial matrix and intermembrane space proteases on yeast aging.

BACKGROUND: In many organisms, aging is characterized by a loss of mitochondrial homeostasis. Multiple factors such as respiratory metabolism, mitochondrial fusion/fission, or mitophagy have been linked to cell longevity, but the exact impact of each one on the aging process is still unclear. RESULTS: Using the deletion mutant collection of the fission yeast Schizosaccharomyces pombe, we have developed a genome-wide screening for mutants with altered chronological lifespan. We have identified four mutants associated with proteolysis at the mitochondria that exhibit opposite effects on longevity. The analysis of the respiratory activity of these mutants revealed a positive correlation between increased respiration rate and prolonged lifespan. We also found that the phenotype of the long-lived protease mutants could not be explained by impaired mitochondrial fusion/fission activities, but it was dependent on mitophagy induction. The anti-aging role of mitophagy was supported by the effect of a mutant defective in degradation of mitochondria, which shortened lifespan of the long-lived mutants. CONCLUSIONS: Our characterization of the mitochondrial protease mutants demonstrates that mitophagy sustains the lifespan extension of long-lived mutants displaying a higher respiration potential.

Repurposing Salicylamides to Combat Phytopathogenic Bacteria and Induce Plant Defense Responses.

Based on the research strategy of "drug repurposing", a series of derivatives and marketed drugs that containing salicylic acid skeleton were tested for their antibacterial activities against phytopathogens. Salicylic acid can not only regulate some important growth metabolism of plants, but also induce plant disease resistance. The bioassay results showed that the salicylamides exhibited excellent antibacterial activity. Especially, oxyclozanide showed the best antibacterial effect against Xanthomonas oryzae, Xanthomonas axonopodis pv. citri and Pectobacterium atroseptica with MICs of 0.78, 3.12 and 12.5 µg.mL-1, respectively. In vivo experiments with rice bacterial leaf blight had further demonstrated that oxyclozanide exhibited stronger antibacterial activity than the commercial bactericide, thiodiazole copper. Oxyclozanide could induce plant defense responses through the determination of salicylic acid content and the activities of defense-related enzymes including CAT, POD, and SOD in rice. The preliminarily antibacterial mechanism study indicated that oxyclozanide exhibited the antibacterial activity by disrupting cell integrity and reducing bacterial pathogenicity. Additionally, oxyclozanide could induce plant defense responses through the determination of salicylic acid content.

Spatially Reprogramed Receptor Organization to Switch Cell Behavior Using a DNA Origami-Templated Aptamer Nanoarray.

Receptor oligomerization is a highly complex molecular process that modulates divergent cell signaling. However, there is a lack of molecular tools for systematically interrogating how receptor oligomerization governs the signaling response. Here, we developed a DNA origami-templated aptamer nanoarray (DOTA) that enables precise programming of the oligomerization of receptor tyrosine kinases (RTK) with defined valency, distribution, and stoichiometry at the ligand-receptor interface. The DOTA allows for advanced receptor manipulations by arraying either monomeric aptamer ligands (mALs) that oligamerize receptor monomers to elicit artificial signaling or dimeric aptamer ligands (dALs) that preorganize the receptor dimer to recapitulate natural activation. We demonstrated that the multivalency and nanoscale spacing of receptor oligomerization coordinately influence the activation level of receptor tyrosine kinase signaling. Furthermore, we illustrated that DOTA-modulated receptor oligomerization could function as a signaling switch to promote the transition from epithelia to mesenchymal-like cells, demonstrating robust control over cellular behaviors. Together, we present a versatile all-in-one DNA nanoplatform for the systematical investigation and regulation of receptor-mediated cellular response.