ZIFs derived polyhedron with cobalt oxide nanoparticles as novel nanozyme for the biomimetic catalytic oxidation of glucose and non-enzymatic sensor.

The global prevalence of diabetes makes it a significant work to develop flagship sensors in glucose monitoring technology. Particularly, exploring highly active nanocomposites as biomimetic catalysts for the enzymatic reaction of glucose is extremely attractive in non-enzymatic glucose sensing. Herein, nitrogen-doped hollow carbon nano-polyhedron implanted with Co3O4 nanoparticles (NHCN-Co3O4) was introduced as nanozyme for the catalytic oxidation of glucose. NHCN-Co3O4 was synthesized by a two-step redox carbonization of zeolitic imidazolate frameworks. Morphology and structure characterizations revealed that NHCN-Co3O4 was a rhombic nano-dodecahedron with hollow N-doped carbon frameworks. In the frameworks, well-defined Co3O4 nanoparticles were embedded. With highly porous N-doped graphitization structure and embedded Co3O4, NHCN-Co3O4 displayed a distinguished biomimetic catalysis towards the direct oxidation of glucose at a low onset potential of 0.30 V. The biomimetic catalysis of glucose oxidation at NHCN-Co3O4 was so efficient that a steady-state current signal could be established within 3 s. By using NHCN-Co3O4 as nanozyme, a brilliant non-enzymatic glucose sensor was developed with a very low detection limit of 0.2 µM and broad detection range from 1.0 µM to 32.0 mM. Besides, NHCN-Co3O4 sensor also displayed an effective anti-interference capability towards the simulated interfering species including small biomolecules, amino acids, and chloride ion. Furthermore, notable repeatability, reproducibility and long-term stability were also presented. Finally, the successful blood sugar detection in human serum strongly manifests the possible real application of NHCN-Co3O4 sensor.

Highly active catalyst using zeolitic imidazolate framework derived nano-polyhedron for the electro-oxidation of l-cysteine and amperometric sensing.

Herein, N-doped porous carbon nano-polyhedron embedded with Co3O4 (Co3O4-NPCN) was reported for the electro-catalytic oxidation and amperometric detection of l-cysteine. Co3O4-NPCN was synthesized by the two-step redox calcination of zeolitic imidazolate framework (ZIF). Surface morphology characterization revealed that Co3O4-NPCN displayed a uniform size and rhombic dodecahedral shape. Structure and composition analysis found that Co3O4-NPCN was a N-doped carbon polyhedral matrix with hollow and porous structure, and Co3O4 nano-spheres were evenly distributed into the polyhedral matrix. Due to the hollow and porous structure, N-doped carbon matrix and embedded Co3O4 nano-spheres, Co3O4-NPCN performed a remarkable electro-catalysis towards the oxidation of l-cysteine at a very low potential of 0.10 V. A diffusion-controlled l-cysteine oxidation process was observed at Co3O4-NPCN prepared electrode. Accordingly, amperometric method was established for l-cysteine detection with a very fast current response in 2 s, wide linear range of 0.05 µM- 5.2 mM and low detection limit of 6.9 nM. Besides, notable selectivity, repeatability, reproducibility and long-term stability were also achieved. Moreover, Co3O4-NPCN sensor was successfully applied to the l-cysteine detection in human serum samples indicating the practical application of the as-developed sensor.

Direct Electrochemical Selenylation/Cyclization of Alkenes: Access to Functionalized Benzheterocycles.

A catalyst-free, environmentally friendly, and efficient electrochemical selenylation/cyclization of alkenes has been developed with moderate to excellent yields. This selenylated transformation proceeds smoothly and tolerates a wide range of synthetically useful groups to deliver diverse functionalized benzheterocycles, including iminoisobenzofuran, lactones, oxindoles, and quinolinones. Moreover, the present synthetic route could also be readily scaled up to gram quantity with convenient operation in an undivided cell.

Nitrogen-doped carbon dodecahedron embedded with cobalt nanoparticles for the direct electro-oxidation of glucose and efficient nonenzymatic glucose sensing.

Developing high-performance sensors for glucose detection is extremely desirable for clinical diagnostics and life sciences. Particularly, it is greatly attractive to exploit composite materials with large surface area, doped heterojunction and non-precious metal as highly active electro-catalysts for nonenzymatic glucose sensing. Herein, we reported a N-doped carbon dodecahedron embedded with Co nanoparticles (Co@NCD) for the direct electro-oxidation of glucose and efficient nonenzymatic glucose detection. Co@NCD was synthesized by the pyrolysis of zeolitic imidazolate framework (ZIF). Field emission scanning electron microscope, high-resolution transmission electron microscope, powder X-ray diffraction, X-ray photoelectron spectroscopy and nitrogen adsorption-desorption experiments were performed to investigate Co@NCD. A well-defined dodecahedron morphology with uniform size and shape was observed. Besides, the original framework was carbonized after pyrolysis leading to a hollow and porous graphite dodecahedron containing N-doped carbon heterojunction. Moreover, Co nanoparticles were evenly distributed into the dodecahedron. With porous structure, N-doped carbon and embedded Co nanoparticles, Co@NCD displayed a notable electro-catalysis towards the direct oxidation of glucose (onset potential: 0.20 V). By using Co@NCD as electro-catalyst, an efficient nonenzymatic glucose sensor was obtained with a rapid amperometric response (within 1 s), low detection limit (0.11 µM) and broad detection range (0.2 µM-12.0 mM). In addition, remarkable selectivity, repeatability, reproducibility and long-term stability were also observed. Finally, Co@NCD prepared sensor was also successfully applied to the detection of glucose in human serum. Our results suggested that ZIF templated method could be an innovative solution for active composite catalysts in biomolecular electro-catalysis and Co@NCD prepared sensor could be a substantial preferable sensing platform for the nonenzymatic glucose detection.

Identification of a novel TNRC18-RARA fusion in acute promyelocytic leukemia lacking t(15;17)(q24;q12)/PML-RARA.

Acute promyelocytic leukemia (APL) is a unique disease entity in acute myeloid leukemia, characterized by PML-RARA fusion gene, which is generated by chromosomal translocation t(15;17)(q24;q21). We identified TNRC18-RARA as novel RARA fusion in resembling APL. Our study highlights the importance of combining multiple molecular techniques to characterize and optimally manage APL lacking classic t(15;17)(q24;q12)/PML-RARA fusion.

Preparation, characterization and in vitro-in vivo evaluation of bortezomib supermolecular aggregation nanovehicles.

BACKGROUNDS: Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients' compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process. METHODS: In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer. RESULTS: Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability. CONCLUSIONS: Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.

Electrochemical Oxidative Phosphorylation of Aldehyde Hydrazones.

The electrochemical phosphorylation of aldehyde hydrazones has been developed under exogenous oxidant-free conditions. The strategy provides expedient access to highly functionalized α-iminophosphine oxides with ample scope and broad functional group tolerance by means of mild, user-friendly electrolysis, in an undivided cell.

Bifunctional and highly sensitive electrochemical non-enzymatic glucose and hydrogen peroxide biosensor based on NiCo2O4 nanoflowers decorated 3D nitrogen doped holey graphene hydrogel.

In this work, a simple strategy for fabricating a 3D nitrogen doped holey graphene hydrogel decorated with NiCo2O4 nanoflowers (NHGH/NiCo2O4) via a one-pot hydrothermal method with subsequent calcination is reported for the first time. The novel NHGH/NiCo2O4 nanocomposites featured high electrical conductivity, large and accessible surface areas, abundant active sites, and excellent electrocatalytic performance. Considering the excellent catalytic activity of NiCo2O4, a sensitive and bifunctional electrochemical non-enzymatic biosensor was established for the determination of glucose and hydrogen peroxide (H2O2). The obtained biosensor exhibited wide linear ranges (glucose: 0.005-10.95 mM; H2O2: 1-510 µM) and a low detection limits (glucose: 0.39 µM; H2O2: 0.136 µM) in alkaline solution (S/N = 3). Excellent electrocatalytic activity of this sensor was ascribed to the synergistic effects of the hybrid structure between the NiCo2O4 nanoflowers and NHGH. Furthermore, the sensitive biosensor also exhibited high selectivity and could be applied to determine glucose in real blood samples. Taken together, the results reveal that the proposed hybrid nanocomposite could be a promising electrochemical biosensor.

Catalyst-Free, Direct Electrochemical Tri- and Difluoroalkylation/Cyclization: Access to Functionalized Oxindoles and Quinolinones.

The catalyst-free electrochemical di- and trifluoromethylation/cyclization of N-substituted acrylamides was realized under external oxidant-free conditions. The strategy provides expedient access to fluoroalkylated oxindoles and 3,4-dihydroquinolin-2(1 H)-ones with ample scope and broad functional group tolerance by mild, direct electrolysis of sodium sulfinates in an undivided cell. Detailed mechanistic studies provided strong support for a SET-based reaction manifold.

A glassy carbon electrode modified with a bismuth film and laser etched graphene for simultaneous voltammetric sensing of Cd(II) and Pb(II).

Polyimide (PI) sheets were laser etched to obtain graphene-based carbon nanomaterials (LEGCNs). These were analyzed by scanning electron microscopy, X-ray diffraction and Raman spectroscopy which confirmed the presence of stacked multilayer graphene nanosheets. Their large specific surface and large number of edge-plane active sites facilitate the accumulation of metal ions. A glassy carbon electrode (GCE) with an in-situ plated bismuth film was modified with the LEGCNs to give a sensor with satisfactory response for the simultaneous determination of cadmium(II) and lead(II) by means of square wave anodic stripping voltammetry. It appears that is the first report on an electrochemical sensor based on the use of laser etched graphene for determination of heavy metal ions. Figures of merit for detection of Cd(II) include (a) a low and well separated working potential of -0.80 V (vs. Ag/AgCl), (b) a wide linear range (from 7 to 120 µg·L-1), and a low detection limits 0.47 µg·L-1. The respective data for Pb(II) are (a) -0.55 V, (b) 5 to 120 µg·L-1, and (c) 0.41 µg·L-1. The modified GCE displays remarkable repeatability, reproducibility, selectivity and stability. The sensor was applied to the simultaneous determination of Cd(II) and Pb(II) in spiked real water samples. The results confirm that the laser etching technique is an efficient tool for the preparation of carbon nanomaterials with high quality and great sensing performance. Graphical abstract Bismuth film and laser etched graphene-modified glassy carbon electrode (BF-LEGCN/GCE) for the simultaneous determination of cadmium(II) and lead(II) by square wave anodic stripping voltammetry.

One pot synthesis of dandelion-like polyaniline coated gold nanoparticles composites for electrochemical sensing applications.

In this work, we report a facile and green strategy for one pot and in-situ synthesis of a dandelion-like conductive polyaniline coated gold nanoparticle nanocomposites (Au@PANI). The Au@PANI was characterized by SEM, TEM, XRD, TGA, FTIR, UV-vis and conductivity measurement, respectively. Newly-designed Au@PANI materials possessed a significantly high conductivity and strong adsorption capability. Thus, the Au@PANI modified glassy carbon electrode (GCE) was utilized for construct a novel electrochemical sensor for the simultaneous assay of Pb2+ and Cu2+ using square wave anodic stripping voltammetry (SWASV). Under the optimized conditions, an excellent electrochemical response in the simultaneous of Pb2+ and Cu2+ with detection limit of 0.003 and 0.008 µM (S/N = 3), respectively. Moreover, the prepared sensors realized an excellent reproducibility, repeatability and long term stability, as well as reliable practical assays in real water samples. Besides, the possible formation mechanism and sensing mechanism of Au@PANI nanocomposites have been discussed in detail. We believe this study provides a novel method of fabrication of noble metal nanoparticles decorated conducting polymer materials for the electrochemical sensing applications.

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression.

The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, which has affected the early diagnosis and treatment of HCC and the survival time of patients. MicroRNAs (miRNAs) are a class of evolutionarily conserved small, non-coding RNAs, which regulate the expression of various genes post-transcriptionally. Emerging evidence indicates that the key enzymes involved in the miRNA biosynthesis pathway and some tumor-specific miRNAs are widely deregulated or upregulated in HCC and closely associated with the occurrence and development of various cancers, including HCC. Early studies have shown that miRNAs have critical roles in HCC progression by targeting many critical protein-coding genes, thereby contributing to the promotion of cell proliferation; the avoidance of apoptosis, inducing via angiogenesis; and the activation of invasion and metastasis pathways. Experimental data indicate that discovery of increasing numbers of aberrantly expressed miRNAs has opened up a new field for investigating the molecular mechanism of HCC progression. In this review, we describe the current knowledge about the roles and validated targets of miRNAs in the above pathways that are known to be hallmarks of HCC, and we also describe the influence of genetic variations in miRNA biosynthesis and genes.

Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression.

Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.

Exploration of the binding mode between (-)-zampanolide and tubulin using docking and molecular dynamics simulation.

The binding mode of (-)-zampanolide (ZMP) to tubulin was investigated using docking, molecular dynamics (MD) simulation, and binding free-energy calculations. The docking studies validated the experimental results indicating that the paclitaxel site is the binding site for (-)-ZMP. The 18 ns MD simulation shows the docking mode has changed a lot, whereas it offers more reliable binding data. MM-PBSA binding free-energy calculations further confirmed the results of the MD simulation. The study revealed that hydrophobic interactions play an important role in stabilizing the binding, and the strong hydrogen bond formed with Asp224 enhances the affinity for tubulin. Meanwhile, the results support the assumption that (-)-ZMP can be attacked by His227, leading to a nucleophilic reaction and covalent binding. These theoretical results lead to a greater understanding of the mechanism of action of binding to tubulin, and will therefore aid the design of new compounds with higher affinities for tubulin.

Docking and molecular dynamics studies of the binding between Peloruside A and tubulin.

The molecular docking, MD simulation and binding free energy calculation were performed to explore the probable binding modes between PLA and tubulin. Through docking study, three possible binding sites for PLA were speculated as follows: the taxane site, the alternative site and a new site in α-tubulin. Then, 12.0 ns MD simulations show that these binding modes predicted by docking have been changed more or less, whereas the MD simulations offer more reliable binding details. The MM-PBSA binding free-energy calculations reasonably identify that the taxane site is the most favorable binding site of PLA and the alternative site is the secondary one, which can be used to explain some experimental facts. These studies theoretically resolve the priority of binding sites for PLA and offer the reliable binding modes between PLA and tubulin, and thus help to understanding the action mechanism for this kind of inhibitor.