Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations

Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering

Table1_Identification of Potential Prognostic Biomarkers Associated With Macrophage M2 Infiltration in Gastric Cancer.DOC

Gastric cancer is a common cancer afflicting people worldwide. Although incremental progress has been achieved in gastric cancer research, the molecular mechanisms underlying remain unclear. In this study, we conducted bioinformatics methods to identify prognostic marker genes associated with gastric cancer progression. Three hundred and twenty-seven overlapping DEGs were identified from three GEO microarray datasets. Functional enrichment analysis revealed that these DEGs are involved in extracellular matrix organization, tissue development, extracellular matrix–receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, focal adhesion, and protein digestion and absorption. A protein–protein interaction network (PPI) was constructed for the DEGs in which 25 hub genes were obtained. Furthermore, the turquoise module was identified to be significantly positively coexpressed with macrophage M2 infiltration by weighted gene coexpression network analysis (WGCNA). Hub genes of COL1A1, COL4A1, COL12A1, and PDGFRB were overlapped in both PPI hub gene list and the turquoise module with significant association with the prognosis in gastric cancer. Moreover, functional analysis demonstrated that these hub genes play pivotal roles in cancer cell proliferation and invasion. The investigation of the gene markers can help deepen our understanding of the molecular mechanisms of gastric cancer. In addition, these genes may serve as potential prognostic biomarkers for gastric cancer diagnosis.</p

Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations

Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering

Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations

Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering

Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations

Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering

Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations

Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering

TiO₂‑Assisted Laser Desorption/Ionization Mass Spectrometry for Rapid Profiling of Candidate Metabolite Biomarkers from Antimicrobial-Resistant Bacteria

Antimicrobial resistance (AMR) is one of the most serious problems affecting public health and safety. It is crucial to understand antimicrobial resistance from the molecular level. In this work, TiO2-assisted laser desorption/ionization (LDI) mass spectrometry (MS) was used for the fast metabolites analysis from intact bacterial cells to discriminate different strains of bacteria and to detect AMR. With the mass spectra of bacterial metabolites by TiO2-LDI MS, multivariable analysis was performed for bacterial identification to determine distinctive metabolites as the potential biomarkers. The most statistically significant metabolites were screened out by the method and further identified using liquid-chromatography (LC) tandem MS (MS/MS). Robustness of our developed methods in bacterial taxonomy was demonstrated by iterative validation using 48 clinical samples. The strategy was further illustrated with three clinical strains of ESBL (extended-spectrum β-lactamase-resistant)-positive Escherichia. coli and four clinical strains of ESBL-negative ones. Eleven key metabolites were identified as potential biomarkers of ESBL-positive E. coli. We also implemented the pathway and network analysis on the key metabolites to prove the feasibility of our method in executing metabolomics analysis. Compared to the most prevalent techniques in a metabolomics study, such as LC-MS, gas chromatography MS, and nuclear magnetic resonance spectroscopy, the current method has advantages in its simple sample preparation and short analysis time, thereby fitting especially into clinical usages and fast analyses

A Bonded Double-Doped Graphene Nanoribbon Framework for Advanced Electrocatalysis

The preparation of a low-cost, high-efficient, and stable electrocatalyst as an alternative to platinum for the oxygen reduction reaction (ORR) is especially important to various energy storage components, such as fuel cells and metal–air batteries. Here, we report a new type of bonded double-doped graphene nanoribbon-based nonprecious metal catalysts in which Fe3C nanoparticles embedded in Fe-N-doped graphene nanoribbon (GNRs) frameworks through a simple pyrolysis. The as-obtained catalyst possesses several desirable merits for the ORR, such as diverse high-efficiency catalytic sites, a high specific surface area, an ideal hierarchical cellular structure, and a highly conductive N-doped GNR network. Accordingly, the prepared catalyst shows a superior ORR activity (an onset potential of 0.02 V and a half-wave potential of −0.148 V versus an Ag/AgCl electrode) in alkaline media, close to the commercial Pt/C catalyst. Moreover, it also displays good ORR behavior in an acidic solution

Dual-Signal Imaging Mode Based on Fluorescence and Electrochemiluminescence for Ultrasensitive Visualization of SARS-CoV‑2 Spike Protein

Accurate and reliable detection of SARS-CoV-2 is critical for the effective prevention and rapid containment of COVID-19. Current approaches suffer from complex procedures or a single signal readout, resulting in an increased risk of false negatives and low sensitivity. Here, we developed a fluorescence (FL) and electrochemiluminescence (ECL) dual-mode imaging platform based on a self-powered DNAzyme walker to achieve accurate surveillance of SARS-CoV-2 spike protein at the single-molecule level. The specific activation of the DNAzyme walker by the target protein provides the power for the system’s continuous running, enabling the simultaneous recording of the reduction in fluorescence spots and the appearance of ECL spots generated by the Ru-doped metal–organic framework (MOF) emitter. Therefore, the constructed imaging platform can achieve dual-mode detection of spike protein via reverse dual-signal feedback, which could effectively eliminate false-positive or false-negative signals and improve the detection accuracy and sensitivity with a low detection limit. In particular, the dual-mode accuracy of spike protein diagnosis in samples has been significantly improved compared to single-signal output means. In addition, this dual-mode imaging platform may become a prospective diagnostic device for other infectious viruses

Copper-Catalyzed Tyrosine Nitration

Tyrosine nitration, often observed during neurodegenerative disorders under nitrative stress, is usually considered to be induced chemically either by nitric oxide and oxygen forming nitrogen dioxide or by the decomposition of peroxynitrite. It can also be induced enzymatically by peroxidases or superoxide dismutases in the presence of both hydrogen peroxide and nitrite forming nitrogen dioxide and/or peroxynitrite. In this study, the role of cupric ions for catalyzing tyrosine nitration in the presence of hydrogen peroxide and nitrite, by a chemical mechanism rather similar to enzymatic pathways where nitrite is oxidized to form nitrogen dioxide, was investigated by development of a microreactor also capable of acting as an emitter for electrospray ionization mass spectrometry analysis. Indeed, cupric ions and peptide–cupric ion complexes are found to be excellent Fenton catalysts, even better than Fe(III) or heme, for the formation of •OH radicals and/or copper(II)-bound •OH radicals from hydrogen peroxide. These radicals are efficiently scavenged by nitrite anions to form •NO2 and by tyrosine to form tyrosine radicals, leading to tyrosine nitration in polypeptides. We also show that cupric ions can catalyze tyrosine nitration from nitric oxide, oxygen, and hydrogen peroxide as the formation of tyrosine radicals is increased in the presence of diffusible and/or copper(II) bound hydroxyl radicals. This study shows that copper has a polyvalent role in the processes of tyrosine nitration