Smart Composite Reagent Composed of Double-Stranded DNA-Templated Copper Nanoparticle and SYBR Green I for Hydrogen Peroxide Related Biosensing

On the basis of an interesting experimental phenomenon, a novel and smart composite reagent consisting of double-stranded DNA-templated copper nanoparticles (dsDNA–CuNPs) and DNA intercalator (SYBR Green I) was developed and exploited for hydrogen peroxide (H₂O₂) detection as well as oxidase-based biosensing. The study found that, within the composite reagent, the small molecule SYBR Green I was easily adsorbed on the surfaces of CuNPs, instead of intercalating into the dsDNA. So the composite reagent only exhibited the red fluorescence generated from dsDNA–CuNPs. However, when the solution of H₂O₂ was added into the composite reagent, the CuNPs were deconstructed and their fluorescence was quenched; meanwhile, the inhibition of SYBR Green I binding with dsDNA was eliminated. As a result, the mixed solution of the composite reagent with H₂O₂ exhibited green fluorescence generated from the intercalation of SYBR Green I into dsDNA. Since H₂O₂ is an important molecule and involved in various research fields, this developed composite reagent could be employed for many applications in biological analysis. As a proof-of-application demonstration, the sensitive detection of glucose was conducted. Moreover, the method was also extended to the detection of other biomolecules, such as cholesterol and horseradish peroxidase, which indicated the broad applications of the proposed sensing strategy in biomedical analysis

Multifunctional Dumbbell-Shaped DNA-Templated Selective Formation of Fluorescent Silver Nanoclusters or Copper Nanoparticles for Sensitive Detection of Biomolecules

In this work, a multifunctional template for selective formation of fluorescent silver nanoclusters (AgNCs) or copper nanoparticles (CuNPs) is put forward. This dumbbell-shaped (DS) DNA template is made up of two cytosine hairpin loops and an adenine–thymine-rich double-helical stem which is closed by the loops. The cytosine loops act as specific regions for the growth of AgNCs, and the double-helical stem serves as template for the CuNPs formation. By carefully investigating the sequence and length of DS DNA, we present the optimal design of the template. Benefiting from the smart design and facile synthesis, a simple, label-free, and ultrasensitive fluorescence strategy for adenosine triphosphate (ATP) detection is proposed. Through the systematic comparison, it is found that the strategy based on CuNPs formation is more sensitive for ATP assay than that based on AgNCs synthesis, and the detection limitation was found to be 81 pM. What’s more, the CuNPs formation-based method is successfully applied in the detection of ATP in human serum as well as the determination of cellular ATP. In addition to small target molecule, the sensing strategy was also extended to the detection of biomacromolecule (DNA), which illustrates the generality of this biosensor

Highly Stable Fluorescent-Traffic-Light Sensor for Point-of-Care Detection of Tetracycline

Fluorescent point-of-care (POC) sensors have found great utility in fields like clinical diagnosis, food testing, and environmental monitoring. Herein, we developed a highly stable POC sensor that enabled the visual detection of tetracycline (TC) in a distinct fluorescent-traffic-light manner. In the sensor, a composite material of copper nanoclusters and metal–organic framework (CuNCs@MOF-5) prepared with a facile one-pot synthetic strategy was employed as the core element for target recognition and signal transduction. As evidenced by experiments, the as-prepared CuNCs@MOF-5 exhibited significantly improved fluorescence properties in terms of emission enhancement (about 28-fold) and stability improvement (over 110 days) compared to the CuNCs without confining and protection by MOF-5. More importantly, it was found that TC could uniquely interact with Zn(II) to trigger the disassembly of CuNCs@MOF-5, resulting in green fluorescence emission from the TC–Zn(II) complex and red fluorescence weakening of CuNCs. On the basis of this finding, a simple and stable sensor was proposed for POC detection of TC, which demonstrated high sensitivity, selectivity, and reproducibility. In addition to homogeneous visual detection in a 96-well plate, a CuNCs@MOF-5-contained agarose gel array was easily fabricated to achieve direct detection of TC in milk without any pretreatment, thanks to the size-sieving effect of the gel. Moreover, a test paper array was also put forward for low-cost TC detection, which indicates the extensibility and practicability of this sensing strategy

Nickel-Catalyzed Regioselective Cleavage of C_sp²–S Bonds: Method for the Synthesis of Tri- and Tetrasubstituted Alkenes

We describe here an efficient route for the synthesis of (<i>Z</i>)-vinylic sulfides <b>3</b> via the highly regio- and stereoselective coupling of (<i>Z</i>)-1,2-bis­(aryl­(alkyl)­thio)­alkenes and Grignard reagents over a Ni catalyst under mild conditions. (<i>Z</i>)-Vinylic sulfides <b>3</b> are important intermediates in the synthesis of tri- and tetrasubstituted alkenes that are important construction blocks for drugs and natural products. The directing organosulfur groups (SR) can be converted to diaryl­(alkyl) disulfides (RSSR) using H₂O₂ as oxidant, hence avoiding the waste of sulfur resources. The protocol provides a general method that is highly regio- and stereoselective for the synthesis of a diversity of tri- and tetrasubstituted alkenes

Periodic Fluorescent Silver Clusters Assembled by Rolling Circle Amplification and Their Sensor Application

A simple method for preparing DNA-stabilized Ag nanoclusters (NCs) nanowires is presented. To fabricate the Ag NCs nanowires, we use just two unmodified component strands and a long enzymatically produced scaffold. These nanowires form at room temperature and have periodic sequence units that are available for fluorescence Ag NCs assembled which formed three-way junction (TWJ) structure. These Ag NCs nanowires can be clearly visualized by confocal microscopy. Furthermore, due to the high efficiency of rolling circle amplification reaction in signal amplification, the nanowires exhibit high sensitivity for the specific DNA detection with a wide linear range from 6 to 300 pM and a low detection limit of 0.84 pM, which shows good performance in the complex serum samples. Therefore, these Ag NCs nanowires might have great potential in clinical and imaging applications in the future

Rational Design of Yolk–Shell CuO/Silicalite-1@mSiO₂ Composites for a High-Performance Nonenzymatic Glucose Biosensor

In this study, an interface coassembly strategy is employed to rationally synthesize a yolk–shell CuO/silicalite-1@void@mSiO₂ composite consisting of silicalite-1 supported CuO nanoparticles confined in the hollow space of mesoporous silica, and the obtained composite materials were used as a novel nonenzymatic biosensor for highly sensitive and selective detecting glucose with excellent anti-interference ability. The synthesis of CuO/silicalite-1@mSiO₂ includes four steps: coating silicalite-1 particles with resorcinol-formaldehyde polymer (RF), immobilization of copper species, interface deposition of a mesoporous silica layer, and final calcination in air to decompose RF and form CuO nanoparticles. The unique hierarchical porous structure with mesopores and micropores is beneficial to selectively enrich glucose for fast oxidation into gluconic acid. Besides, the mesopores in the silica shell can effectively inhibit the large interfering substances or biomacromolecules diffusing into the void as well as the loss of CuO nanoparticles. The hollow chamber inside serves as a nanoreactor for glucose oxidation catalyzed by the active CuO nanoparticles, which are spatially accessible for glucose molecules. The nonenzymatic glucose biosensors based on CuO/silicalite-1@mSiO₂ materials show excellent electrocatalytic sensing performance with a wide linear range (5–500 μM), high sensitivity (5.5 μA·mM^–1·cm^–2), low detection limit (0.17 μM), and high selectivity against interfering species. Furthermore, the unique sensors even display a good capability in the determination of glucose in real blood serum samples

DataSheet9_Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis.ZIP

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.</p

DataSheet2_Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis.ZIP

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.</p

DataSheet5_Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis.ZIP

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.</p

DataSheet3_Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis.ZIP

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.</p