DNAzymes are a promising platform for metal ion detection, and a few DNAzyme‐based sensors have been reported to detect metal ions inside cells. However, these methods required an influx of metal ...ions to increase their concentrations for detection. To address this major issue, the design of a catalytic hairpin assembly (CHA) reaction to amplify the signal from photocaged Na+‐specific DNAzyme to detect endogenous Na+ inside cells is reported. Upon light activation and in the presence of Na+, the NaA43 DNAzyme cleaves its substrate strand and releases a product strand, which becomes an initiator that trigger the subsequent CHA amplification reaction. This strategy allows detection of endogenous Na+ inside cells, which has been demonstrated by both fluorescent imaging of individual cells and flow cytometry of the whole cell population. This method can be generally applied to detect other endogenous metal ions and thus contribute to deeper understanding of the role of metal ions in biological systems.
Cha cha cha: A catalytic hairpin assembly (CHA) reaction was designed to amplify the signal from photocaged Na+‐specific DNAzyme cleavage to detect endogenous Na+ inside cells. After light activation and in the presence of Na+, the NaA43 DNAzyme cleaves its substrate strand and releases a product strand, which becomes an initiator that can trigger the subsequent CHA signal amplification reaction.
Topological phases of matter connect mathematical principles to real materials, and may shape future electronic and quantum technologies. So far, this discipline has mostly focused on single-gap ...topology described by topological invariants such as Chern numbers. Here, based on a tunable kagome model, we observe non-Abelian band topology and its transitions in acoustic semimetals, in which the multi-gap Hilbert space plays a key role. In non-Abelian semimetals, the topological charges of band nodes are converted through the braiding of nodes in adjacent gaps, and their behaviour cannot be captured by conventional topological band theory. Using kagome acoustic metamaterials and pump–probe measurements, we demonstrate the emergence of non-Abelian topological nodes, identify their dispersions and observe the induced multi-gap topological edge states. By controlling the geometry of the metamaterials, topological transitions are induced by the creation, annihilation, merging and splitting of band nodes. This reveals the underlying rules for the conversion and transfer of non-Abelian topological charges in multiple bandgaps. The resulting laws that govern the evolution of band nodes in non-Abelian multi-gap systems should inspire studies on multi-band topological semimetals and multi-gap topological out-of-equilibrium systems.Non-Abelian topology allows topological charges in multi-gap systems to be converted by braiding of different band nodes. Such multi-gap effects are experimentally observed in an acoustic semimetal.
Direct measurement of DNA repair is critical for the annotation of their clinical relevance and the discovery of drugs for cancer therapy. Here we reported a “repaired and activated” DNAzyme ...(RADzyme) by incorporating a single methyl lesion (O6MeG, 3MeC, or 1MeA) at designated positions through systematic screening. We found that the catalytic activity of the RADzyme was remarkably suppressed and could be restored via enzyme‐mediated DNA repair. Benefit from these findings, a fluorogenic RADzyme sensor was developed for the monitoring of MGMT‐mediated repair of O6MeG lesion. Importantly, the sensor allowed the evaluation of MGMT repair activity in different cells and under drugs treatment. Furthermore, another RADzyme sensor was engineered for the monitoring of ALKBH2‐mediated repair of 3MeC lesion. This strategy provides a simple and versatile tool for the study of the basic biology of DNA repair, clinical diagnosis and therapeutic assessment.
We report “repaired and activated” DNAzymes (RADzymes) as a simple and versatile platform for the measurement of multiple DNA alkylation repair in living cells. The catalytic activity of RADzymes was remarkably suppressed and could be restored via enzyme‐mediated DNA repair, thus providing a useful strategy for the study of DNA repair, clinical diagnosis and therapeutic assessment.
The genetic manipulation of basidiomycete mushrooms is notoriously difficult and immature, and there is a lack of research reports on clustered regularly interspaced short palindromic repeat (CRISPR) ...based gene editing of functional genes in mushrooms. In this work,
Ganoderma lucidum
, a famous traditional medicinal basidiomycete mushroom, which produces a type of unique triterpenoid-anti-tumor ganoderic acids (GAs), was used, and a CRISPR/CRISPR-associated protein-9 nuclease (Cas9) editing system for functional genes of GA biosynthesis was constructed in the mushroom. As proof of concept, the effect of different gRNA constructs with endogenous
u6
promoter and self-cleaving ribozyme HDV on
ura3
disruption efficiency was investigated at first. The established system was applied to edit a cytochrome P450 monooxygenase (CYP450) gene
cyp5150l8
, which is responsible for a three-step biotransformation of lanosterol at C-26 to ganoderic acid 3-hydroxy-lanosta-8, 24-dien-26 oic acid. As a result, precisely edited
cyp5150l8
disruptants were obtained after sequencing confirmation. The fermentation products of the wild type (WT) and
cyp5150l8
disruptant were analyzed, and a significant decrease in the titer of four identified GAs was found in the mutant compared to WT. Another CYP gene involved in the biosynthesis of squalene-type triterpenoid 2, 3; 22, 23-squalene dioxide,
cyp505d13
, was also disrupted using the established CRISPR-Cas9 based gene editing platform of
G. lucidum
. The work will be helpful to strain molecular breeding and biotechnological applications of
G. lucidum
and other basidiomycete mushrooms.
Recent Advances on DNAzyme-Based Sensing Huang, Zhimei; Wang, Xiangnan; Wu, Zhenkun ...
Chemistry, an Asian journal,
March 14, 2022, Letnik:
17, Številka:
6
Journal Article
Recenzirano
Owing to the high sensitivity, excellent programmability, and flexible obtainment through in vitro selection, RNA-cleaving DNAzymes have attracted increasing interest in developing DNAzyme-based ...sensors. In this review, we summarize the recent advances on DNAzyme-based sensing applications. We initially conclude two general strategies to expand the library of DNAzmes, in vitro selection to discover new DNAzymes towards different targets of interest and chemical modifications to endue the existing DNAzymes with new function or properties. We then discuss the recent applications of DNAzyme-based sensors for the detection of a variety of important biomoleucles both in vitro and in vivo. Finally, perspectives on the challenges and future directions in the development of DNAzyme-based sensors are provided.
Polymer‐based dielectrics are attracting increasing attention due to their high‐density energy storage. However, mitigating the heat generation in real capacitors has been a challenge. Here an ...electrothermal breakdown phase‐field model is developed to fundamentally understand the thermal effects on the dielectric breakdown of polymer‐based dielectrics in real capacitor configurations including the increase in the dielectric loss and the decrease in the breakdown strength. While both enhancing the thermal conductivity and reducing the electrical conductivity of the polymer nanocomposites can reduce the thermal effects, it is found that reducing the electrical conductivity is more effective. This work is expected to not only stimulate attention to the thermal effects in polymer‐based dielectrics but also provide a fundamental guidance to mitigate the heat‐induced deterioration of breakdown strength.
An electrothermal breakdown phase‐field model is developed to fundamentally understand the thermal effects on the breakdown behavior of polymer‐based dielectrics with different microstructures. The predicted temperature‐dependent breakdown strengths agree with the available experimental measurements. It is found that reducing the electrical conductivity is more effective than enhancing the thermal conductivity of the polymer nanocomposite to reduce the thermal effects.
Developing highly efficient chemodynamic therapy (CDT)-based theranostic technology for cancer treatment is highly desired but still challenging. A novel nanotheranostic platform is constructed for ...enhanced CDT by engineering hybrid CaO2 and Fe3O4 nanoparticles with a hyaluronate acid (HA) stabilizer and NIR fluorophore label. This design not only enables the nanotheranostic agent to afford highly efficient CDT against tumor cells but also confers NIR fluorescence (NIRF) and magnetic resonance (MR) bimodal imaging for in vivo visualization of CDT. Moreover, the use of the HA stabilizer allows for the facile synthesis of the nanotheranostic agent with excellent biocompatibility and active targetability. The nanotheranaostic agent possesses a high capacity of self-supplying H2O2 and producing •OH in acidic conditions, while retaining the desired stability under physiological conditions. It also demonstrates high selectivity to tumor cells via CDT with minimized toxicity to normal cells. In vivo studies reveal that our nanotheranaostic agent exhibits efficacious tumor growth inhibition via a CDT mechanism with favorable biosafety. Moreover, in vivo visualization of the CDT progress via NIRF and MR bimodal imaging demonstrates specific targeting and treatment of tumors. The developed H2O2 self-supplying, active targeting, and bimodal imaging nanotheranostic platform holds the potential as a highly efficient strategy for CDT of cancer.
Ageing, an unanswered question in the medical field, is a multifactorial process that results in a progressive functional decline in cells, tissues and organisms. Although it is impossible to prevent ...ageing, slowing down the rate of ageing is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life and its role in anti‐ageing is getting more and more attention. This article summarizes the work done on the natural products from TCM that are reported to have anti‐ageing effects, in the past two decades. The effective anti‐ageing ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, alkaloids and others. Astragaloside, Cistanche tubulosa acteoside, icariin, tetrahydrocurcumin, quercetin, butein, berberine, catechin, curcumin, epigallocatechin gallate, gastrodin, 6‐Gingerol, glaucarubinone, ginsenoside Rg1, luteolin, icarisid II, naringenin, resveratrol, theaflavin, carnosic acid, catalpol, chrysophanol, cycloastragenol, emodin, galangin, echinacoside, ferulic acid, huperzine, honokiol, isoliensinine, phycocyanin, proanthocyanidins, rosmarinic acid, oxymatrine, piceid, puerarin and salvianolic acid B are specified in this review. Simultaneously, chemical structures of the monomers with anti‐ageing activities are listed, and their source, model, efficacy and mechanism are also described. The TCMs with anti‐ageing function are classified according to their action pathways, including the telomere and telomerase, the sirtuins, the mammalian target of rapamycin, AMP‐activated kinase and insulin/insulin‐like growth factor‐1 signalling pathway, free radicals scavenging and the resistance to DNA damage. Finally, Chinese compound prescription and extracts related to anti‐ageing are introduced, which provides the basis and the direction for the further development of novel and potential drugs.
Linked Articles
This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Inorganic cesium lead iodide perovskite CsPbI3 is attracting great attention as a light absorber for single or multi‐junction photovoltaics due to its outstanding thermal stability and proper band ...gap. However, the device performance of CsPbI3‐based perovskite solar cells (PSCs) is limited by the unsatisfactory crystal quality and thus severe non‐radiative recombination. Here, vacuum‐assisted thermal annealing (VATA) is demonstrated as an effective approach for controlling the morphology and crystallinity of the CsPbI3 perovskite films formed from the precursors of PbI2, CsI, and dimethylammonium iodide (DMAI). By this method, a large‐area and high‐quality CsPbI3 film is obtained, exhibiting a much reduced trap‐state density with prolonged charge lifetime. Consequently, the solar cell efficiency is raised from 17.26 to 20.06 %, along with enhanced stability. The VATA would be an effective approach for fabricating high‐performance thin‐film CsPbI3 perovskite optoelectronics.
A vacuum‐assisted thermal annealing approach is employed for the fabrication of CsPbI3 perovskite films with full surface coverage and enhanced crystallization. The resultant CsPbI3 perovskite solar cells exhibit a power conversion efficiency (PCE) as high as 20.06 %, along with enhanced long‐term stability.
Exploiting an intelligent fluorescent probe, which can precisely target to the lysosome of hepatoma cells and enable accurate molecular imaging, is a key challenge in hepatoma diagnoses. Herein, a ...single-dye-based polymer nanoprobe (named SPN) with dual-targeting and self-calibrating ratiometric characteristics is rationally fabricated via a simple self-assembly strategy for accurate hypochlorous acid (HClO) imaging in the lysosome of HepG2 cells. Of note, the covalent incorporation of self-calibrating ratiometric fluorophore (pyrene derivatives) into the core of polymer nanoparticles can not only validly avoid the leakage of fluorophores but also greatly enhance their brightness. Besides, this polymer nanoprobe (SPN) displays high water dispersibility, ultrafast response (<1s), favorable selectivity, outstanding long-term stability (>90 days), and good biocompatibility. Furthermore, thanks to the hepatocyte-targeting moiety (galactose) and the interplay of surface charge and size of nanoparticles, the SPN is able to enter into asialoglycoprotein receptor-positive HepG2 cells and further locate at lysosomes, successfully enabling accurate HClO detection in lysosomes of HepG2 cells. This study demonstrates that the versatile SPN can provide more precise dual-targeting and accurate molecular imaging.
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