Magnesium ion selective two-photon fluorescent probe based on a benzo[h]chromene derivative for in vivo imaging

A novel, two-photon probe for the detection of free Mg2+ ions in living cells and live tissues has been developed. The probe can be excited by 880 nm laser photons, emits strong two-photon excited fluorescence in response to Mg2+ ions, can be easily loaded into the cell and tissue, shows high photostability, and can measure the Mg2+ ion concentration without interference by Ca2+ ions in living cells. The intracellular dissociation constant (Kdi) for Mg2+ determined by the two-photon process is 2.5 mM, which is suitable for dynamic Mg2+ concentration measurement. In addition, the probe is capable of imaging endogenous stores of free Mg2+ at a few hundred micrometers depth in live tissues using two-photon microscopy (TPM).     

A computational study on the interaction of the nitric oxide ions NO+ and NO- with the side groups of the aromatic amino acids

The interaction of the nitric oxide ions NO+ and NO- with benzene (C6H6) and the aromatic R-groups of the amino acids phenylalanine (Phe), tyrosine (Tyr), histidine (His), and tryptophan (Trp) have been examined using the DFT method B3LYP and the conventional electron correlation method MP2. In particular, the structures and complexation energies of the resulting half-sandwich Ar...NO+/- and sandwich [Ar...NO...Ar]+/- complexes have been considered. For the Ar...NO+ complexes, the presence of an electron rich heteroatom within or attached to the ring is found to not preclude the cation...pi bound complex from being the most stable. Furthermore, unlike the anionic complexes, the pi...cation...pi ([Ar...NO...Ar]+) complexes do not correspond to a "doubling" of the parent half-sandwich.     

Nano-sized lithium manganese oxide dispersed on carbon nanotubes for energy storage applications

Nano-sized lithium manganese oxide (LMO) dispersed on carbon nanotubes (CNT) has been synthesized successfully via a microwave-assisted hydrothermal reaction at 200 °C for 30 min using MnO₂-coated CNT and an aqueous LiOH solution. The initial specific capacity is 99.4 mAh/g at a 1.6 C-rate, and is maintained at 99.1 mAh/g even at a 16 C-rate. The initial specific capacity is also maintained up to the 50th cycle to give 97% capacity retention. The LMO/CNT nanocomposite shows excellent power performance and good structural reversibility as an electrode material in energy storage systems, such as lithium-ion batteries and electrochemical capacitors. This synthetic strategy opens a new avenue for the effective and facile synthesis of lithium transition metal oxide/CNT nanocomposite.     

Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I,and the Chemotherapeutic Drug,Temozolomide against Glioblastoma Tumorspheres

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.     

Enhanced Physical and Mechanical Properties of Nitrile-Butadiene Rubber Composites with N-Cetylpyridinium Bromide-Carbon Black

The physical and mechanical properties of nitrile–butadiene rubber (NBR) composites with N-cetylpyridinium bromide-carbon black (CPB-CB) were investigated. Addition of 5 parts per hundred rubber (phr) of CPB-CB into NBR improved the tensile strength by 124%, vulcanization rate by 41%, shore hardness by 15%, and decreased the volumetric wear by 7% compared to those of the base rubber-CB composite.     

Loganin Alleviates Gout Inflammation by Suppressing NLRP3 Inflammasome Activation and Mitochondrial Damage

Gout is a type of inflammatory arthritis caused by the deposition of monosodium uric acid (MSU) crystals in tissues. The etiology of gout is directly linked to the NLRP3 inflammasome, since MSU crystals are NLRP3 inflammasome activators. Therefore, we decided to search for a small-molecule inhibitor of the NLRP3 inflammasome for the prevention of gout inflammation. We found that loganin suppressed MSU crystals-induced caspase-1 (p20) and interleukin (IL)-1β production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks formation in mouse primary macrophages, showing its ability to inhibit the NLRP3 inflammasome. In an air pouch inflammation model, oral administration of loganin to mice prevented MSU crystals-induced production of mature IL-1β and IL-18 in air pouch exudates, resulting in decreased neutrophil recruitment. Furthermore, oral administration of loganin suppressed MSU crystals-induced gout inflammation in a mouse foot gout model, which was accompanied by the inhibition of the NLRP3 inflammasome. Loganin blocked de novo synthesis of mitochondrial DNA in air pouches and foot tissues injected with MSU crystals. Consistently, loganin prevented MSU crystals-induced mitochondrial damage in macrophages, as it increased mitochondrial membrane potential and decreased the amount of mitochondrial reactive oxygen species. These data demonstrate that loganin suppresses NLRP3 inflammasome activation by inhibiting mitochondrial stress. These results suggest a novel pharmacological strategy to prevent gout inflammation by blocking NLRP3 inflammasome activation and mitochondrial dysfunction.     

Substituent Effects on the Vibrational Properties of the CN Stretch Mode of Aromatic Nitriles: IR Probes Useful for Time-resolved IR Spectroscopy

Developing ideal IR probes is essential to understand the structure and dynamics of biomolecules with time-resolved IR spectroscopies and imaging techniques. Especially, nitrile (CN) group has recently been proposed to serve as IR probes of the local environment of proteins. Herein, we investigated the effect of a substituent on the vibrational properties of the benzonitrile. The electron-donating and withdrawing character of p-substituent on benzonitrile are expected to modulate the vibrational frequency, molar extinction coefficient, and vibrational lifetime of CN probe. FT-IR revealed the positive correlation between electron-donating character and the molar extinction coefficient of CN stretch mode. Infrared pump-probe (IR-PP) measurements showed that the vibrational lifetime of CN stretch mode exhibits a relatively weak correlation with the electron-donating strength. Among the investigated samples, 4-dimethylamino benzonitrile with the strongest electron-donating strength shows enhanced absorption and extended vibrational lifetime. Utilizing substituent effects will be a practical strategy to improve the performance of the IR probe.     

Accelerated hydrolysis of esters catalyzed by receptors, II. Degradation of RNA by polyvinylpyrrolidone

The nonenzymatic hydrolysis of RNA by polyvinylpyrrolidone (PVP) has been investigated. A bell-shaped kinetics was observed when the first order rate constant of the reaction was ploted as a function of PVP concentration, which means the kinetic feature of PVP as a degradative receptor distinct from those of degradative enzymes (e.g., ribonuclease).     

A novel synthesis of benzo[c]phenanthridine skeleton and biological evaluation of isoquinoline derivatives.

Benzo[c]phenanthridine skeleton was synthesized from easily available starting N-methyl-o-toluamide 2 and o-methylbenzonitrile 5 in 7 steps. Radical cyclization of styrene 10 afforded 6,11-dimethyl-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one 13. Most 3-arylisoquinolines have displayed strong activities against human tumor cell lines. Especially, indenoisoquinolinone 13 exhibited excellent cytotoxicity (IC50 = 0.002 microgram/ml; HCT 15).     

Tuning Local Coordination Environments of Manganese Single-Atom Nanozymes with Multi-Enzyme Properties for Selective Colorimetric Biosensing

Single-atom nanozymes (SAzymes) are promising in next-generation nanozymes, nevertheless, how to rationally modulate the microenvironment of SAzymes with controllable multi-enzyme properties is still challenging. Herein, we systematically investigate the relationship between atomic configuration and multi-enzymatic performances. The constructed Mn_SA−N₃-coordinated SAzymes (Mn_SA−N₃−C) exhibits much more remarkable oxidase-, peroxidase-, and glutathione oxidase-like activities than that of Mn_SA−N₄−C. Based on experimental and theoretical results, these multi-enzyme-like behaviors are highly dependent on the coordination number of single atomic Mn sites by local charge polarization. As a consequence, a series of colorimetric biosensing platforms based on Mn_SA−N₃−C SAzymes is successfully built for specific recognition of biological molecules. These findings provide atomic-level insight into the microenvironment of nanozymes, promoting rational design of other demanding biocatalysts.