Single-atom nanozymes with peroxidase-like activity: A review.

Single-atom nanozymes (SANs) are nanomaterials-based nanozymes with atomically dispersed enzyme-like active sites. SANs offer improved as well as tunable catalytic activity. The creation of extremely effective SANs and their potential uses have piqued researchers' curiosity due to their advantages of cheap cost, variable catalytic activity, high stability, and large-scale production. Furthermore, SANs with uniformly distributed active centers and definite coordination structures offer a distinctive opportunity to investigate the structure-activity correlation and control the geometric and electrical features of metal centers. SANs have been extensively explored in photo-, thermal-, and electro-catalysis. However, SANs suffer from the following disadvantages, such as efficiency, non-mimicking of the 3-D complexity of natural enzymes, limited and narrow range of artificial SANs, and biosafety aspects. Among a quite limited range of artificial SANs, the peroxidase action of SANs has attracted significant research attention in the last five years with the aim of producing reactive oxygen species for use in cancer therapy, and water treatment among many other applications. In this review, we explore the recent progress of different SANs as peroxidase mimics, the role of the metal center in enzymatic activity, possible prospects, and underlying limitations in real-time applications.

Metallomics and NMR-based metabolomics of Chlorella sp. reveal the synergistic role of copper and cadmium in multi-metal toxicity and oxidative stress.

Industrial wastewaters often contain high levels of metal mixtures, in which metal mixtures may have synergistic or antagonistic effects on aquatic organisms. A combination of metallomics and nuclear magnetic resonance spectroscopy (NMR)-based metabolomics was employed to understand the consequences of multi-metal systems (Cu, Cd, Pb) on freshwater microalgae. Morphological characterization, cell viability and chlorophyll a determination of metal-spiked Chlorella sp. suggested synergistic effects of Cu and Cd on growth inhibition and toxicity. While Pb has no apparent effect on Chlorella sp. metabolome, a substantial decrease of sucrose, amino acid content and glycerophospholipid precursors in Cu-spiked microalgae revealed Cu-induced oxidative stress. Addition of Cd to Cu-spiked cultures induced more drastic metabolic perturbations, hence we confirmed that Cu and Cd synergistically influenced photosynthesis inhibition, oxidative stress and membrane degradation. Total elemental analysis revealed a significant decrease in K, and an increase in Na, Mg, Zn and Mn concentrations in Cu-spiked cultures. This indicated that Cu is more toxic to Chlorella sp. as compared to Cd or Pb, and the combination of Cu and Cd has a strong synergistic effect on Chlorella sp. oxidative stress induction. Oxidative stress is confirmed by liquid chromatography tandem mass spectrometry analysis, which demonstrated a drastic decrease in the GSH/GSSG ratio solely in Cu-spiked cultures. Interestingly, we observed Cu-facilitated Cd and Pb bioconcentration in Chlorella sp. The absence of phytochelatins and an increment of extracellular polymeric substances (EPS) yields in Cu-spiked cultures suggested that the mode of bioconcentration of Cd and Pb is through adsorption of free metals onto the algal EPS rather than intracellular chelation to phytochelatins.

Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase.

Cell movement requires forces generated by non-muscle myosin II (NM II) for coordinated protrusion and retraction. The Cdc42/Rac effector MRCK regulates a specific actomyosin network in the lamella essential for cell protrusion and migration. Together with the Rho effector ROK required for cell rear retraction, they cooperatively regulate cell motility and tumour cell invasion. Despite the increasing importance of ROK inhibitors for both experimental and clinical purposes, there is a lack of specific inhibitors for other related kinases such as MRCK. Here, we report the identification of chelerythrine chloride as a specific MRCK inhibitor. Its ability to block cellular activity of MRCK resulted in the specific loss of NM II-associated MLC phosphorylation in the lamella, and the consequential suppression of cell migration.

Elevation of human alpha-defensins and S100 calcium-binding proteins A8 and A9 in tear fluid of patients with pterygium.

PURPOSE: The pathogenesis of pterygia is still not well understood. Recent studies suggest that it may be associated with inflammation and progressive proliferation triggered by ultraviolet radiation. In this study the authors determined that the inflammatory nature of pterygium is reflected in the protein components of tears. METHODS: Consent for this study was obtained from 12 patients (average age, 57 years; eight men, four women) with unilateral pterygium. Tears were collected from diseased eyes and contralateral healthy control eyes with the use of fire-polished 10-microL calibrated glass pipettes before pterygium surgery. Tear protein profiles obtained from diseased and control eyes (seven patient samples) were compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. Tears from another five patients with pterygium were used for subsequent protein identification experiments with nano-LC coupled with nano-electrospray tandem mass spectrometry (nano-ESI-MS/MS). RESULTS: SELDI mass spectra showed that one peptide cluster with a molecular weight of 3.4 kDa and two proteins with molecular weights of 10.8 kDa and 12.7 kDa were elevated in tears of eyes with pterygium. Proteins of interest were identified by nano-LC-ESI-MS/MS as human alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, HNP-3) and S100 calcium-binding proteins A8 and A9. Mean concentrations (n = 7) of alpha-defensins were 1.33 +/- 0.47 microg/mL (HNP-1, P < 0.015) and 0.61 +/- 0.23 microg/mL (HNP-2, P < 0.012) for pterygium eyes and 0.17 +/- 0.12 microg/mL (HNP-1) and 0.02 +/- 0.02 microg/mL (HNP-2) for fellow control eyes. Compared with tears from eyes without pterygium or other abnormalities, the level of S100 A8 increased 1.4- to 13.4-fold (average fold change, 4.5) and S100 A9 increased 1.5- to 4.0-fold (average fold change, 2.3) in 4 of 7 patients. CONCLUSIONS: The upregulated expression of human alpha-defensins and S100 A8 and A9 in tear fluids of patients with pterygium indicates that they may be part of the response of the ocular surface to the formation of this fibrovascular tissue or the accompanying inflammation. They may also serve as a useful indicator for predicting recurrent pterygium.

Clinical analysis by microchip capillary electrophoresis.

Clinical analysis often requires rapid, automated, and high-throughput analytical systems. Microchip capillary electrophoresis (CE) has the potential to achieve very rapid analysis (typically seconds), easy integration of multiple analytical steps, and parallel operation. Although it is currently still in an early stage of development, there are already many reports in the literature describing the applications of microchip CE in clinical analysis. At the same time, more fully automated and higher throughput commercial instruments for microchip CE are becoming available and are expected to further enhance the development of applications of microchip CE in routine clinical testing. To put into perspective its potential, we briefly compare microchip CE with conventional CE and review developments in this technique that may be useful in diagnosis of major diseases.