Laborious and costly detection of miRNAs has brought challenges to its practical applications, especially for home health care, rigorous military medicine, and the third world. In this work, we ...present a pH-responsive miRNA amplification method, which allows the detection of miRNA just using a pH test paper. The operation is easy and no other costly instrument is involved, making the method very friendly. In our strategy, a highly efficient isothermal amplification of miRNA is achieved using an improved netlike rolling circle amplification (NRCA) technique. Large amounts of H+ can be produced as a byproduct during the amplification to induce significant changes of pH, which can be monitored directly using a pH test paper or pH-sensitive indicators. The degree of color changes depends on the amount of miRNA, making it possible for quantitative analysis. As an example, the method is successfully applied to quantify a miRNA (miR-21) in cancer cells. The results agree well with that from the prevalent qRT-PCR analysis. It is the first time that a paper-based point-of-care testing (POCT) is developed for the detection of miRNAs, which might promote the popularization of miRNAs working as biomarkers for diagnostic purposes.
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IJS, KILJ, NUK, PNG, UL, UM
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide-drug conjugates (PDCs) constructed by modifying antitumor drugs with ...peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (
T7-SS-DOX and
T7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand
T7 (HAIYPRH) and its retro-inverso analog
T7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the
T7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to
T7-SS-DOX. In conclusion, the coupling of antitumor drugs with the
T7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nanozymes have received great attention owing to the advantages of easy preparation and low cost. Unlike natural enzymes that readily adapt to physiological environments, artificial nanozymes are apt ...to passivate in complex clinical samples （e.g., serum）, which may damage the catalytic capability and consequently limit the application in biomedical analysis. To conquer this problem, in this study, we fabricated novel nanozyme@DNA hydrogel architecture by incorporat~ng nanozymes into a pure DNA hydrogel. Gold nanoparticles （AuNPs） were adopted as a model nanozyme. Results indicate that AuNPs incorporated in the DNA hydrogel retain their catalytic capability in serum as they are protected by the hydrogel, whereas AuNPs alone totally lose the catalytic capability in serum. The detection of hydrogen peroxide and glucose in serum based on the catalysis of the AuNPs@DNA hydrogel was achieved. The detection limit of each reaches 1.7 and 38 ~M, respectively, which is equal to the value obtained using natural enzymes. Besides the mechanisms, some other advantages, such as recyclability and availability, have also been explored. This nanozyme@DNA hydrogel architecture may have a great potential for the utilization of nanozymes as well as the application of nanozymes for biomedical analysis in complex physiological samples.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A luminescent metal-organic framework of type Eu(III)-MOF has been fabricated for visual and on-site fluorometric determination of hydrogen peroxide (H
2
O
2
) via a tablet computer. The maximum ...excitation and emission peaks of type Eu(III)-MOF were found at λex = 290 nm and λem = 615 nm, respectively. The average length of Eu-MOF is 1.21 ± 0.07 μm. In the presence of the target H
2
O
2
, Fe
2+
is transmitted into Fe
3+
via Fenton reaction, leading to a fluorescence quenching of Eu-MOF. Therefore, visible color change occurred from bright red into colorless. Interestingly, by means of tablet computer’s digital camera and ImageJ software, fluorescent signals were captured and transduced into digital parameters, resulting in a linear relationship between fluorescence intensity and the concentration of H
2
O
2
. As a result, the determination of H
2
O
2
without the aid of complicated instruments is achieved in the range 2.0 μM to 0.2 mM with a detection limit of 1.02 μM. Our approach has been successfully applied to quantify H
2
O
2
in serum, urine, and waste water with good recovery and precision (< 2.5% RSD). Besides, our assay has been exploited for visual detection of H
2
O
2
released from HepG2 cells with the advantages of portability and accuracy. Moreover, the strategy displays acceptable selectivity and stability. Hence, our assay provides an alternative practical method for on-site determination of H
2
O
2
without the need for instruments.
Graphical abstract
Schematic representation of the synthesis procedure of a luminescent Eu-MOF, which has been successfully applied for on-site detection of H
2
O
2
via Fenton reaction and imaging analysis technique. The method exhibits handheld and accuracy for H
2
O
2
determination, holding the potential for biochemical and clinical applications in remote regions.
A method is presented that uses photoinduced electron transfer (PET) for the determination of microRNAs (miRNAs) in clinical serum samples and complicated cell samples by using a smartphone. miRNA-21 ...is adopted as a model analyte. A 3′-phosphorylated DNA probe containing AgNCs is synthesized and hybridized with miRNA-21. Subsequently, the probe is cleaved specifically by duplex-specific nuclease to form 3′-hydroxylated products, then extended by terminal deoxynucleotidyl transferase (TdT) with superlong G for G-quadruplex/hemin units fabrication. In this way, PET occurred between AgNCs and produced G-quadruplex/hemin units, leading to the fluorescence quenching of AgNCs. Notably, the fluorescence images can be captured and translated into digital information by smartphone, resulting in a direct quantitative determination of miRNA. As a result, our strategy for miRNA assay is achieved with a satisfactory detection limit of 1.43 pM. Interestingly, TdT-propelled G-quadruplex/hemin units as multiple electron acceptors promote the sensitivity of miRNA monitoring. Different miRNAs assays are realized by adjusting the complimentary sequences of DNA probe. These qualities not only broaden the practical application of PET-based strategy, but also provide a new insight into the nucleic acid detection.
Graphical abstract
Schematic representation of AgNCs and enzyme-propelled photoinduced electron transfer strategy. It has been successfully applied for detection of miRNA by image analysis software. The method displays portability and accuracy for miRNA determination, meeting the potential for biochemical and clinical applications in resource-limited settings.
Abstract
Baicalin magnesium is a water-soluble compound isolated from the aqueous solution by
Scutellaria baicalensis
Georgi. Preliminary experiments have demonstrated that baicalin magnesium can ...exert protective effects against acute liver injury in rats induced by carbon tetrachloride or lipopolysaccharide combined with d-galactose by regulating lipid peroxidation and oxidative stress. The aim of this study was to investigate the protective effect of baicalin magnesium on non-alcoholic steatohepatitis (NASH) in rats and to elucidate the underlying mechanisms. NASH was induced through a high-fat diet (HFD) for 8 weeks, and Sprague-Dawley rats were intravenously injected with baicalin magnesium, baicalin, and magnesium sulfate for 2 weeks, respectively. Serum was obtained for biochemical analyses and the determination of oxidative stress indicators. Liver tissues were collected for use in liver index assessment, histopathological examination, inflammatory factor analysis, and protein and gene expression analysis. The results revealed that baicalin magnesium markedly improved HFD-induced lipid deposition, inflammatory response, oxidative stress, and histopathological impairments. And baicalin magnesium may exert a protective effect on NASH rats by inhibiting the NLR family pyrin domain involving the 3 (NLRP3)/caspase-1/interleukin (IL)-1
β
inflammatory pathway. Additionally, the effect of baicalin magnesium was remarkably superior to that of equimolar baicalin and magnesium sulfate in regard to ameliorating NASH symptoms. In conclusion, the findings suggested that baicalin magnesium may represent a potential drug for the treatment of NASH.
A β-glucosidase gene designated gluc3m was cloned through construction of a genomic library of Martelella mediterranea 2928. The gluc3m consisted of 2,496 bp and encoded a peptide of 832 amino acids ...that shared the greatest amino acid similarity (59%) with a β-glucosidase of family 3 glycoside hydrolase from Agrobacterium radiobacter K84. The optimum reaction temperature and pH of Gluc3M were 45 °C and 8.0, respectively. The K m and V max for p-nitrophenyl-β-d-glucopyranoside were 0.18 mg/ml and 196.08 µmol/min/mg enzyme, respectively. Gluc3M was found to be highly alkali stable, retaining 80% of its maximum enzymatic activity after treatment with pH 11.0 buffers for 24 h. Furthermore, the activity of Gluc3M improved remarkably in the presence of univalent metal ions, whereas it was inhibited in the presence of divalent ions. Gluc3M also exhibited significant activities toward various substrates including pNPGlu, pNPGal, salicin, and konjac powder. It is important to note that Gluc3M is a cold-active enzyme that showed over 50% of the maximum enzymatic activity at 4 °C. SWISS-MODEL revealed that the amino acids near the conserved domain SDW of Gluc3M contributed to the cold-active ability. Based on these characteristics, Gluc3M has the potential for use in additional studies and for industrial applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•A visible method is designed for qualitative and quantitative analysis of ctDNA.•The method is based on ctDNA-induced and DNAzyme-functionalized hydrogel.•The detection limit of ctDNA is 0.32 ...pM.•ctDNA concentrations in spiked plasma samples are accurately assayed.
Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive access of tumor dynamics. However, most existing ctDNA analysis strategies depend on costly instrument. Therefore, we here report a visible strategy for ctDNA detection based on ctDNA-triggered and DNAzyme-functionalized hydrogel. On one hand, target ctDNA triggers the rolling circle amplification and finally synthesizes a DNA hydrogel with G-quadruplex structures, which as 3D macroscopical material could be observed easily by naked eye. On the other hand, by utilizing the DNAzyme activity of the G-quadruplex/heme complex, the hydrogel could catalyze the colorless ABTS to green oxidative product ABTS*. Quantitating ctDNA thus can be achieved by observing the color change. Our strategy for ctDNA detection is sensitive in a concentration from 1 pM to 10 nM and limit of detection down to 0.32 pM. Moreover, our visible strategy has been successfully applied to the simulate analysis of clinical blood samples. Importantly, our method does not require expensive equipment, thus not only exhibiting great potential application in some harsh circumstances with limited medical conditions, but also opening new insight into the development of visible detection method of DNA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Low redox kinetics and shuttle effect of polysulfides (PSs) is a grand challenge for practical applications of lithium-sulfur (Li-S) batteries. Herein, cobalt (Co) nanoparticles embedded inside ...nitrogen (N)-doped hierarchical porous carbon (MgCo-HC) are prepared via one-pot approach. As a result, MgCo-HC unique structure with the large surface area and Co, N-doping is proposed for the strong physical/chemical adsorption of PSs, high conductivity, fast redox reaction kinetics and the high S utilization. The resultant S cathode delivers a high specific capacity of 1086.4 mA h/g at 0.1 C, low-capacity fading rate of 0.041% per cycle over 880 cycles at 2 C, and superior rate performance up to 5 C. More intriguingly, the S/MgCo-HC electrode delivers reversible area capacities of 5.1 and 5.5 mA h/cm2 at 0.1 C under high S loading and learn electrolyte condition, respectively. Furthermore, the assembled Li-S soft-packaged battery is also readily assembled, which highlights stable electrochemical properties under folding conditions. This work provides a simple strategy to design advanced S hosts for the practical application of Li-S batteries with excellent electrochemical performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer stem cells (CSCs) are recognized as an important source of cancers. Surface biomarkers play a critical role for CSCs profiling and also for diagnostic purposes. In this paper, we propose ...self-assembled supramolecular nanocomposites assisted multiple signal amplification strategy, and successfully apply it in electrochemical detection of an important CSCs biomarker CD44 as well as identification of breast CSCs. A supermolecular composite, consisting of a binding peptide that is able to bind to the target CD44 and a self-assembled diphenylalanine (FF) nanostructure that provides a template for deposition of gold nanoparticles (AuNPs), is elaborately constructed on the surface of an electrode through the linkage of cucurbit8urils. In the presence of CD44, this supramolecule is able to provide amplified electrochemical signals from silver-enhancement on AuNPs after target-protection from trypsin-catalyzed digestion. Whereas in the absence of the target, this supramolecular architecture is destroyed, resulting in suppressed signals. Linear sweep voltammetry results present a satisfactory specificity and sensitivity, which also demonstrate a wide linear range with a limit of detection of 2.17 pg/mL toward CD44 protein and a limit of detection of 8 cells/mL toward CD44-positive cancer cells. Therefore, this work provides a promising prospective for further clinic application in the future.
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•Specific recognition of breast cancer stem cell biomarker CD44 using binding peptide rather than antibody.•Signal amplification using supramolecular nanocomposites as a scaffold.•Synthesis of self-assembled supramolecular nanocomposites by host-guest interaction.•Successful application in sensitively monitoring breast cancer stem cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
