RESUMO
Dynamic chemical modifications of RNA represent novel and fundamental mechanisms that regulate stemness and tissue homeostasis. Rejuvenation and wound repair of mammalian skin are sustained by epidermal progenitor cells, which are localized within the basal layer of the skin epidermis. N6 -methyladenosine (m6 A) is one of the most abundant modifications found in eukaryotic mRNA and lncRNA (long noncoding RNA). In this report, we survey changes of m6 A RNA methylomes upon epidermal differentiation and identify Pvt1, a lncRNA whose m6 A modification is critically involved in sustaining stemness of epidermal progenitor cells. With genome-editing and a mouse genetics approach, we show that ablation of m6 A methyltransferase or Pvt1 impairs the self-renewal and wound healing capability of skin. Mechanistically, methylation of Pvt1 transcripts enhances its interaction with MYC and stabilizes the MYC protein in epidermal progenitor cells. Our study presents a global view of epitranscriptomic dynamics that occur during epidermal differentiation and identifies the m6 A modification of Pvt1 as a key signaling event involved in skin tissue homeostasis and wound repair.
Assuntos
Adenosina/análogos & derivados , Diferenciação Celular , Células Epidérmicas/citologia , Processamento Pós-Transcricional do RNA , RNA Longo não Codificante/metabolismo , Células-Tronco/citologia , Adenosina/metabolismo , Animais , Células Cultivadas , Células Epidérmicas/metabolismo , Células Epidérmicas/fisiologia , Cobaias , Metiltransferases/genética , Camundongos , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Células-Tronco/metabolismo , Células-Tronco/fisiologia , CicatrizaçãoRESUMO
ConspectusSelf-assembly, a spontaneous process that organizes disordered constituents into ordered structures, has revolutionized our fundamental understanding of living matter, nanotechnology, and molecular science. From the perspective of nanomaterials, self-assembly serves as a bottom-up method for creating long-range-ordered materials. This is accomplished by tailoring the geometry, chemistry, and interactions of the components, thereby facilitating the efficient fabrication of high-quality materials and high-performance functional devices. Over the past few decades, we have seen controllable organization and diverse phases in self-assembled materials, such as organic crystals, biomolecular structures, and colloidal nanoparticle supercrystals. However, most self-assembled ordered materials and their assembly mechanisms are derived from constituents in a liquid bulk medium, where the effects of boundaries and interfaces are negligible. In the context of nanostructure patterning, self-assembly occurs in confined spaces, with feature sizes ranging from a few to hundreds of nanometers. In such settings, ubiquitous boundaries and interfaces can trap the system in a kinetically favored but metastable state, devoid of long-range order. This makes it extremely difficult to achieve ordered structures in micro/nano-patterning techniques that rely on sessile microdroplets, such as inkjet printing, dip-pen lithography, and contact printing.In stark contrast to sessile droplets, capillary bridgesâformed by liquids confined between two solid surfacesâprovide unique opportunities for understanding the long-range-ordered self-assembly of crystalline materials under spatial confinement. Because capillary bridges are stabilized by Laplace pressure, which is inversely proportional to the feature size, the confinement and manipulation of solutions or suspensions of functional materials at the nanoscale become accessible through the rational design of surface chemistry and geometry. Although global thermodynamic equilibrium is unattainable in evaporative systems, ordered nucleation and packing of constituent components can be locally realized at the contact line of capillary bridges. This enables the unprecedented fabrication of long-range-ordered micro/nanostructures with deterministic patterns.In this Account, we review the advancements in long-range-ordered self-assembly of crystalline micro/nanostructures under confinement. First, we briefly introduce crystalline materials characterized by strong intramolecular interactions and relatively weak intermolecular forces, analyzing both the opportunities and challenges inherent to self-assembled nanomaterials. Next, we delve into the construction and manipulation of confined liquids, focusing especially on capillary bridges controlled by engineered chemistry and geometry to regulate Laplace pressure. Through this approach, we have achieved capillary bridges with thicknesses on the order of a few nanometers and wafer-scale homogeneity, facilitating the self-assembly of ordered structures. Supported by factors such as local free-volume entropy, electrostatic interactions, curvilinear geometry, directional microfluidics, and nanoconfinement, we have achieved long-range-ordered, deterministic patterning of organic semiconductors, metal-halide perovskites, and colloidal nanocrystal superlattices using this capillary-bridge platform. These long-range microstructures serve as a bridge between nanomaterials and integrated devices, enabling emergent functionalities like intrinsic stretchability, giant photoconductivity, propagating and interacting exciton polaritons, and spin-valley-locked lasing, which are otherwise unattainable in disordered materials. Finally, we discuss potential directions for both the fundamental understanding and practical applications of confined self-assembly.
RESUMO
The remodeling and stiffening of the extracellular matrix (ECM) is a well-recognized modulator of breast cancer progression. How changes in the mechanical properties of the ECM are converted into biochemical signals that direct tumor cell migration and metastasis remain poorly characterized. Here, we describe a new role for the autophagy-inducing serine/threonine kinases ULK1 and ULK2 in mechanotransduction. We show that ULK1/2 activity inhibits the assembly of actin stress fibers and focal adhesions (FAs) and as a consequence impedes cell contraction and migration, independent of its role in autophagy. Mechanistically, we identify PXN/paxillin, a key component of the mechanotransducing machinery, as a direct binding partner and substrate of ULK1/2. ULK-mediated phosphorylation of PXN at S32 and S119 weakens homotypic interactions and liquid-liquid phase separation of PXN, impairing FA assembly, which in turn alters the mechanical properties of breast cancer cells and their response to mechanical stimuli. ULK1/2 and the well-characterized PXN regulator, FAK/Src, have opposing functions on mechanotransduction and compete for phosphorylation of adjacent serine and tyrosine residues. Taken together, our study reveals ULK1/2 as important regulator of PXN-dependent mechanotransduction.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Paxilina/metabolismo , Mecanotransdução Celular , Fosforilação , Movimento Celular , Serina/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
BACKGROUND: The NAC TF family is widely involved in plant responses to various types of stress. Red clover (Trifolium pratense) is a high-quality legume, and the study of NAC genes in red clover has not been comprehensive. The aim of this study was to analyze the NAC gene family of red clover at the whole-genome level and explore its potential role in the Pb stress response. RESULTS: In this study, 72 TpNAC genes were identified from red clover; collinearity analysis showed that there were 5 pairs of large fragment replicators of TpNAC genes, and red clover was found to be closely related to Medicago truncatula. Interestingly, the TpNAC genes have more homologs in Arabidopsis thaliana than in soybean (Glycine max). There are many elements in the TpNAC genes promoters that respond to stress. Gene expression analysis showed that all the TpNAC genes responded to Pb stress. qRT-PCR showed that the expression levels of TpNAC29 and TpNAC42 were significantly decreased after Pb stress. Protein interaction network analysis showed that 21 TpNACs and 23 other genes participated in the interaction. In addition, the TpNAC proteins had three possible 3D structures, and the secondary structure of these proteins were mainly of other types. These results indicated that most TpNAC members were involved in the regulation of Pb stress in red clover. CONCLUSION: These results suggest that most TpNAC members are involved in the regulation of Pb stress in red clover. TpNAC members play an important role in the response of red clover to Pb stress.
Assuntos
Genoma de Planta , Trifolium , Trifolium/genética , Fatores de Transcrição/genética , Chumbo , Perfilação da Expressão GênicaRESUMO
Integrated electronics and optoelectronics based on organic semiconductors have attracted considerable interest in displays, photovoltaics, and biosensing owing to their designable electronic properties, solution processability, and flexibility. Miniaturization and integration of devices are growing trends in molecular electronics and optoelectronics for practical applications, which requires large-scale and versatile assembly strategies for patterning organic micro/nano-structures with simultaneously long-range order, pure orientation, and high resolution. Although various integration methods have been developed in past decades, molecular electronics still needs a versatile platform to avoid defects and disorders due to weak intermolecular interactions in organic materials. In this perspective, a roadmap of organic integration technologies in recent three decades is provided to review the history of molecular electronics. First, we highlight the importance of long-range-ordered molecular packing for achieving exotic electronic and photophysical properties. Second, we classify the strategies for large-scale integration of molecular electronics through the control of nucleation and crystallographic orientation, and evaluate them based on factors of resolution, crystallinity, orientation, scalability, and versatility. Third, we discuss the multifunctional devices and integrated circuits based on organic field-effect transistors (OFETs) and photodetectors. Finally, we explore future research directions and outlines the need for further development of molecular electronics, including assembly of doped organic semiconductors and heterostructures, biological interfaces in molecular electronics and integrated organic logics based on complementary FETs.
RESUMO
Chiral three-dimensional (3D) perovskites exhibit exceptional optoelectronic characteristics and inherent chiroptical activity, which may overcome the limitations of low-dimensional chiral optoelectronic devices and achieve superior performance. The integrated chip of high-performance arbitrary polarized light detection is one of the aims of chiral optoelectronic devices and may be achieved by chiral 3D perovskites. Herein, we first fabricate the wafer-scale integrated full-Stokes polarimeter by the synergy of unprecedented chiral 3D perovskites (R/S-PyEA)Pb2Br6 and one-step capillary-bridge assembly technology. Compared with the chiral low-dimensional perovskites, chiral 3D perovskites present smaller exciton binding energies of 57.3 meV and excellent circular dichroism (CD) absorption properties, yielding excellent circularly polarized light (CPL) photodetectors with an ultrahigh responsivity of 86.7 A W-1, an unprecedented detectivity exceeding 4.84 × 1013 Jones, a high anisotropy factor of 0.42, and high-fidelity CPL imaging with 256 pixels. Moreover, the anisotropic crystal structure also enables chiral 3D perovskites to have a large linear-polarization response with a polarized ratio of 1.52. The combination of linear-polarization and circular-polarization discrimination capabilities guarantees the achievement of a full-Stokes polarimeter. Our study provides new research insights for the large-scale patterning wafer integration of high-performance chiroptical devices.
RESUMO
Allostery is a phenomenon where the binding of a ligand at one allosteric site influences the affinity for another ligand at an active site. Different from orthosteric regulation, it allows for more precise control of biomolecular activity and enhances the stability of the molecules. Inspired by allosteric regulation of natural molecules, we present a Y-shaped allosteric DNA nanodevice, termed YssAP, that was pH-responsive and functionalized with the AS1411 aptamer for accurate fluorescence imaging of human apurinic/apyrimidinic endonuclease (APE1) activity in tumor cells. With rational design, YssAP could not be cut by APE1, and Cy5 was in the proximity of BHQ2, leading to suppressed signal emission. In contrast, since acidic pH acted as an allosteric effector, YssAP underwent a conformational change into an activated DNA probe (YdsAP) at acidic extracellular pH. After entering the tumor cell via the specific recognition of AS1411 aptamer, the overexpressed APE1 in the tumor cell cut the AP site on YdsAP. Cy5 moved far away from BHQ2, resulting in a strong signal output. Compared with the direct construction of the APE1 substrate, allosteric DNA nanodevices have more accurate imaging effects, which can be precisely adjusted by changing the switching state. We anticipate that this strategy will be applied in the screening of APE1 inhibitors and precise tumor diagnosis.
RESUMO
Accurate and rapid imaging of tumor cells is of vital importance for early cancer diagnosis and intervention. Aptamer-based fluorescence sensors have become a potent instrument for bioimaging, while false positives and on-target off-tumors linked to single-biomarker aptasensors compromise the specificity and sensitivity of cancer imaging. In this paper, we describe a sequential response aptasensor for precise cancer cell identification that is based on a DNA "AND" logic gate. Specifically, the sensor consists of three single-stranded DNA, including the P-strand that can sensitively respond to an acid environment, the L-strand containing the ATP aptamer sequence, and the R-strand for target cell anchoring. These DNA strands hybridize with one another to create a Y-shaped structure (named Y-ALGN). The aptamer in the R-strand is utilized to anchor the sensor to the target cell membrane primarily. Responding to the extracellular acidic environment of the tumor (input 1), the I-motif sequence forms a tetramer structure so that the P-strand is released from the Y-shaped structure and exposes the ATP binding sites in the L-strand. Extracellular ATP, as input 2, continuously operates the DNA aptasensor to complete the logic computation. Upon the sequential response of both protons and ATP molecules, the aptasensor is activated with restored fluorescence on a particular cancer cell membrane. Benefiting from the precise computation capacity of the "AND" logic gate, the Y-ALGN aptasensor can distinguish between MCF-7 cells and normal cells with high accuracy. As a simple and dual-stimuli-responsive strategy, this nanodevice would offer a fresh approach for accurately diagnosing tumor cells.
Assuntos
Aptâmeros de Nucleotídeos , Membrana Celular , Aptâmeros de Nucleotídeos/química , Humanos , Membrana Celular/química , Membrana Celular/metabolismo , Técnicas Biossensoriais/métodos , Trifosfato de Adenosina/análise , Trifosfato de Adenosina/metabolismo , Imagem Óptica , Corantes Fluorescentes/química , DNA de Cadeia Simples/química , Células MCF-7RESUMO
Fiber crossbars, an emerging electronic device, have become the most promising basic unit for advanced smart textiles. The demand for highly sensitive fiber crossbar sensors (FCSs) in wearable electronics is increased. However, the unique structure of FCSs presents challenges in replicating existing sensitivity enhancement strategies. Aiming at the sensitivity of fiber crossbar sensors, a second-order synergistic strategy is proposed that combines air capacitance and equipotential bodies, resulting in a remarkable sensitivity enhancement of over 20 times for FCSs. This strategy offers a promising avenue for the design and fabrication of FCSs that do not depend on intricate microstructures. Furthermore, the integrative structure of core-sheath fibers ensures a robust interface, leading to a low hysteresis of only 2.33% and exceptional stability. The outstanding capacitive response performance of FCSs allows them to effectively capture weak signals such as pulses and sounds. This capability opens up possibilities for the application of FCSs in personalized health management, as demonstrated by wireless monitoring systems based on pulse signals.
RESUMO
Layered metal-halide perovskites, a category of self-assembled quantum wells, are of paramount importance in emerging photonic sources, such as lasers and light-emitting diodes (LEDs). Despite high trap density in two-dimensional (2D) perovskites, efficient non-radiative energy funneling from wide- to narrow-bandgap components, sustained by the Förster resonance energy transfer (FRET) mechanism, contributes to efficient luminescence by light or electrical injection. Herein, it is demonstrated that bandgap extension of layered perovskites to the blue-emitting regime will cause sluggish and inefficient FRET, stemming from the tiny spectral overlap between different phases. Motivated by the importance of blue LEDs and inefficient energy transfer in materials with phase polydispersity, wide-bandgap quasi-2D perovskites with narrow phase distribution, improved crystallinity, and the pure crystal orientation perpendicular to the charge transport layer are developed. Based on this emitter, high-performance blue perovskite LEDs with improved electroluminescence (EL) external quantum efficiency (EQE) of 7.9% at 478 nm, a narrow full width at half-maximum (FWHM) of 22 nm and a more stable EL spectra are achieved. These results provide an important insight into spectrally stable and efficient blue emitters and EL devices based on perovskites.
RESUMO
Coactivator-associated arginine methyltransferase 1 (CARM1) is significant as a key member of the PRMT family, crucial for regulating arginine methylation, and its association with colorectal cancer underscores its potential as a therapeutic target. Consequently, CARM1 inhibitors have emerged as potential therapeutic agents in cancer treatment and valuable chemical tools for cancer research. Despite steady progress in CARM1 inhibitor research, challenges persist in discovering effective, isoform-selective, cell-permeable, and in vivo-active CARM1 inhibitors for colorectal cancer. This review summarizes the research progress on CARM1 and its relationship with colorectal cancer, aiming to provide a theoretical basis for the radiotherapy of colorectal cancer.
Assuntos
Neoplasias Colorretais , Proteína-Arginina N-Metiltransferases , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Maleic anhydride (MAH)-modified polymers are used as tie layers for binding dissimilar polymers in multilayer polymer films. The MAH chemistry which promotes adhesion is well characterized in the bulk; however, only recently has the interfacial chemistry been studied. Sum frequency generation vibrational spectroscopy (SFG) is an interfacial spectroscopy technique which provides detailed information on interfacial chemical reactions, species, and molecular orientations and has been essential for characterizing the MAH chemistry in both nylon and ethyl vinyl alcohol copolymer (EVOH) model systems and coextruded multilayer films. Here, we further characterize the interfacial chemistry between MAH-modified polyethylene tie layers and both EVOH and nylon by investigating the model systems over a range of MAH concentrations. We can detect the interfacial chemical reaction products between MAH and the barrier layer at MAH concentrations of ≥0.022 wt % for nylon and ≥0.077 wt % for EVOH. Additionally, from the concentration-dependent reaction reactant/product SFG peak positions and the product imide or ester/acid CâO group tilt angles extracted from the polarization-dependent SFG spectra, we quantitatively observe concentration-dependent changes to both the interfacial chemistry and interfacial structure. The interfacial chemistry and molecular orientation as a function of MAH concentration are well correlated with the adhesion strength, providing important quantitative information for the future design of MAH-modified tie layers for a variety of important applications.
RESUMO
Silicone elastomers are widely used in many industrial applications, including coatings, adhesives, and sealants. Room-temperature vulcanized (RTV) silicone, a major subcategory of silicone elastomers, undergoes molecular structural transformations during condensation curing, which affect their mechanical, thermal, and chemical properties. The role of reactive hydroxyl (-OH) groups in the curing reaction of RTV silicone is crucial but not well understood, particularly when multiple sources of hydroxyl groups are present in a formulated product. This work aims to elucidate the interfacial molecular structural changes and origins of interfacial reactive hydroxyl groups in RTV silicone during curing, focusing on the methoxy groups at interfaces and their relationship to adhesion. Sum frequency generation (SFG) vibrational spectroscopy is an in situ nondestructive technique used in this study to investigate the interfacial molecular structure of select RTV formulations at the buried interface at different levels of cure. The primary sources of hydroxyl groups required for interfacial reactions in the initial curing stage are found to be those on the substrate surface rather than those from the ingress of ambient moisture. The silylation treatment of silica substrates eliminates interfacial hydroxyl groups, which greatly impact the silicone interfacial behavior and properties (e.g., adhesion). This study establishes the correlation between interfacial molecular structural changes in RTV silicones and their effect on adhesion strength. It also highlights the power of SFG spectroscopy as a unique tool for studying chemical and structural changes at RTV silicone/substrate interface in situ and in real time during curing. This work provides valuable insights into the interfacial chemistry of RTV silicone and its implications for material performance and application development, aiding in the development of improved silicone adhesives.
RESUMO
Silicones have excellent material properties and are used extensively in many applications, ranging from adhesives and lubricants to electrical insulation. To ensure strong adhesion of silicone adhesives to a wide variety of substrates, silane-based adhesion promotors are typically blended into the silicone adhesive formulation. However, little is known at the molecular level about the true silane adhesion promotion mechanism, which limits the ability to develop even more effective adhesion promoters. To understand the adhesion promotion mechanism of silane molecules at the molecular level, this study has used sum frequency generation vibrational spectroscopy (SFG) to determine the behavior of (3-glycidoxypropyl)trimethoxy silane (γ-GPS) at the buried interface between poly(ethylene terephthalate) (PET) and a bulk silicone adhesive. To complement and extend the SFG results, atomistic molecular dynamics (MD) simulations were applied to investigate molecular behavior and interfacial interaction of γ-GPS at the silicone/PET interface. Free energy computations were used to study the γ-GPS interaction in the sample system and determine the γ-GPS interfacial segregation mechanism. Both experiments and simulations consistently show that γ-GPS molecules prefer to segregate at the interface between PET and PDMS. The methoxy groups on γ-GPS molecules orient toward the PDMS polymer phase. The consistent picture of interfacial structure emerging from both simulation and experiment provides enhanced insight on how γ-GPS behaves in the silicone - PET system and illustrates why γ-GPS could improve the adhesion of silicone adhesive, leading to further understanding of silicone adhesion mechanisms useful in the design of silicone adhesives with improved performance.
RESUMO
Antenna, as a converter, could receive and convert signals from the outside world flexibly. Inspired by the behavior of antennas receiving external signals, we developed a pH-stimulated and aptamer-anchored Y-shaped DNA nanoantenna (termed pH-Apt-YNA) for sensitive and specific sensing of tumor extracellular pH gradients. The nanoantenna consisted of three functional nucleic acid sequences, an I-strand, Apt-Y-R and Y-L-G, where the I-strand endowed the DNA nanoantenna with the ability to receive and convert signals, the Apt-Y-R containing an aptamer fragment gave the DNA nanoantenna the ability to specifically anchor target tumor cells, and the complementarity of Y-L-G with the other two sequences ensured the stability of the DNA nanoantenna. Initially, the DNA nanoantenna was in a "silent" state, and rhodamine green was close to BHQ2, leading to suppressed signal emission. When the DNA nanoantenna anchored on the surface of target cancer cells through the aptamer recognition domain, the I-strand tended to fold into a hairpin-contained i-motif tetramer structure owing to the extracellular low pH stimuli, resulting in the DNA nanoantenna changing into an "active" state. In the meantime, rhodamine green moved far away from BHQ2, resulting in a strong signal output. The results demonstrate that the pH-Apt-YNA presents a sensitive pH sensing capacity within a narrow pH range of 6.2-7.4 and exhibits excellent specificity for the imaging of target cancer cell extracellular pH. Based on these advantages, we therefore anticipate that our facile design of the DNA nanoantenna with sensitive responsiveness provides a new way and great promise in the application of sensing pH-related physiological and pathological processes.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Neoplasias , Humanos , Força Próton-Motriz , DNA/química , Rodaminas/química , Oligonucleotídeos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodosRESUMO
Sum frequency generation vibrational spectroscopy (SFG) was applied to characterize the interfacial adhesion chemistry at several buried polymer interfaces in both model systems and blown multilayer films. Anhydride/acid modified polyolefins are used as tie layers to bond dissimilar polymers in multilayer barrier structures. In these films, the interfacial reactions between the barrier polymers, such as ethylene vinyl alcohol (EVOH) or nylon, and the grafted anhydrides/acids provide covalent linkages that enhance adhesion. However, the bonding strengths vary for different polymer-tie layer combinations. Here, using SFG, we aim to provide a systematic study on four common polymer-tie interfaces, including EVOH/polypropylene-tie, EVOH/polyethylene-tie, nylon/polypropylene-tie, and nylon/polyethylene-tie, to understand how the adhesion chemistry varies and its impact on the measured adhesion. Our SFG studies suggest that adhesion enhancement is driven by a combination of reaction kinetics and the interfacial enrichment of the anhydride/acid, resulting in stronger adhesion in the case of nylon. This observation matches well with the higher adhesion observed in the nylon/tie systems in both lap shear and peel test measurements. In addition, in the polypropylene-tie systems, grafted oligomers due to chain scission may migrate to the interface, affecting the adhesion. These by-products can react or interfere with the barrier-tie chemistry, resulting in reduced adhesion strength in the polypropylene-tie system.
RESUMO
BACKGROUND: Aeromonas species are opportunistic pathogens distributed widely in the ecosystem. They are known to be capable of acquiring antibiotic resistance genes, including those encoding proteins against last-line antibiotics, such as the tmexCD-toprJ, mcr and carbapenemase genes. We investigated the genomic and phenotypic characteristics of tmexCD-toprJ-positive Aeromonas strains collected from human, animals, and water samples, particularly those from hospital wastewater in China. METHODS: Samples were collected from living animals, meat, water and human. Aeromonas strains in these samples were isolated in selective media. Antimicrobial resistance profiles of all Aeromonas strains were tested by the broth microdilution method. The presence of tmexCD-toprJ was verified by polymerase chain reaction (PCR). All tmexCD-toprJ-positive (n = 36) and selected tmexCD-toprJ-negative (n = 18) Aeromonas strains were subjected to whole genome sequencing. Carriage of antimicrobial resistance genes, the genetic environment of tmexCD-toprJ and genetic diversity of tmexCD-toprJ-positive Aeromonas strains were determined by bioinformatics analysis. Phylogenetic tree of the Aeromonas strains was built by using the Harvest Suite. FINDINGS: Among the 636 Aeromonas strains isolated from different sources, 36 were positive for tmexCD-toprJ, with the highest prevalence of tmexCD-toprJ being found in fishes (8.8%, 95 CI% 3.6-17.2%), followed by hospital wastewater (6.5%, 95 CI% 4.3-9.3%), river water (2.0%, 0.1-10.9) and duck (1.2%, 95 CI% 3.6-17.2%). All tmexCD-toprJ-positive Aeromonas strains carried multiple antimicrobial resistance genes and exhibited resistance to different classes of antibiotics. Co-existence of tmexCD-toprJ, mcr and blaKPC-2 were identified in 21 strains. The tmexCD-toprJ-positive Aeromonas strains were genetically diverse and found to belong to four different species that could be clustered into three major lineages. The tmexCD-toprJ gene clusters were predominantly located in the chromosome (35/36) of Aeromonas spp., with only one strain carrying the plasmid-borne tmexCD-toprJ cluster. The tmexCD-toprJ genes were associated with seven different types of genetic environments, each of which carried distinct types of mobile elements that may be responsible for mediating transmission of this gene cluster.
Assuntos
Aeromonas , Animais , Humanos , Aeromonas/genética , Antibacterianos/farmacologia , Esgotos , Águas Residuárias , Ecossistema , Filogenia , Testes de Sensibilidade Microbiana , Água , Farmacorresistência Bacteriana/genéticaRESUMO
The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.
Assuntos
Insulina , Concentração de Íons de Hidrogênio , Insulina/química , Técnicas Biossensoriais/métodos , Íons/químicaRESUMO
The reprogramming of cell signaling and behavior through the artificial control of cell surface receptor oligomerization shows great promise in biomedical research and cell-based therapy. However, it remains challenging to achieve combinatorial recognition in a complicated environment and logical regulation of receptors for desirable cellular behavior. Herein, we develop a logic-gated DNA nanodevice with responsiveness to multiple environmental inputs for logically controlled assembly of heterogeneous receptors to modulate signaling. The "AND" gate nanodevice uses an i-motif and an ATP-binding aptamer as environmental cue-responsive units, which can successfully implement a logic operation to manipulate receptors on the cell surface. In the presence of both protons and ATP, the DNA nanodevice is activated to selectively assemble MET and CD71, which modulate the HGF/MET signaling, resulting in cytoskeletal reorganization to inhibit cancer cell motility in a tumor-like microenvironment. Our strategy would be highly promising for precision therapeutics, including controlled drug release and cancer treatment.
Assuntos
DNA , Neoplasias , Humanos , DNA/genética , Oligonucleotídeos , Transdução de Sinais , Neoplasias/tratamento farmacológico , Trifosfato de Adenosina , Microambiente TumoralRESUMO
Respiration and body temperature are largely influenced by the highly contagious influenza virus, which poses persistent global public health challenges. Here, we present a wireless all-in-one sensory face mask (WISE mask) made of ultrasensitive fibrous temperature sensors. The WISE mask shows exceptional thermosensitivity, excellent breathability, and wearing comfort. It offers highly sensitive body temperature monitoring and respiratory detection capabilities. Capitalizing on the advances in the Internet of Things and artificial intelligence, the WISE mask is further demonstrated by customized flexible circuitry, deep learning algorithms, and a user-friendly interface to continuously recognize the abnormalities of both the respiration and body temperature. The WISE mask represents a compelling approach to tracing flu symptom progression in a cost-effective and convenient manner, serving as a powerful solution for personalized health monitoring and point-of-care systems in the face of ongoing influenza-related public health concerns.