Design, synthesis and the structure-activity relationship of agonists targeting on the ALDH2 catalytic tunnel.

ALDH2, a key enzyme in the alcohol metabolism process, detoxifies several kinds of toxic small molecular aldehydes, which induce severe organ damages. The development of novel Alda-1 type ALDH2 activators was mostly relied on HTS but not rational design so far. To clarify the structure-activity relationship (SAR) of the skeleton of Alda-1 analogs by synthesis of the least number of analogs, we prepared 31 Alda-1 analogs and 3 isoflavone derivatives and evaluated for their ALDH2-activating activity. Among these, the ALDH2-activating activity of mono-halogen-substituted (Cl and Br) N-piperonylbenzamides 3b and 3 k, and non-aromatic amides 8a-8c, were 1.5-2.1 folds higher than that of Alda-1 at 20 µM. The relationship between binding affinity in computer aided molecular docking model and the ALDH2-activating activity assays were clarified as follows: for Alda-1 analogs, with the formation of halogen bonds, the enzyme-activating activity was found to follow a specific regression curve within the range between -5 kcal/mol and -4 kcal/mol. For isoflavone derivatives, the basic moiety on the B ring enhance the activating activity. These results provide a new direction of utilizing computer-aided modeling to design novel ALDH2 agonists in the future.

Enhanced electrical properties of amorphous In-Sn-Zn oxides through heterostructuring with Bi2Se3 topological insulators.

Amorphous indium tin zinc oxide (a-ITZO)/Bi2Se3 nanoplatelets (NPs) were fabricated using a two-step procedure. First, Bi2Se3 NPs were synthesized through thermal chemical vapor deposition at 600 °C on a glass substrate, and then a-ITZO was deposited on the surface of the Bi2Se3 NPs via magnetron sputtering at room-temperature. The crystal structures of the a-ITZO/Bi2Se3 NPs were determined via X-ray diffraction spectroscopy and high-resolution transmission electron microscopy. The elemental vibration modes and binding energies were measured using Raman spectroscopy and X-ray photoelectron spectroscopy. The morphologies were examined using field-emission scanning electron microscopy. The electrical properties of the a-ITZO/Bi2Se3 NPs were evaluated using Hall effect measurements. The bulk carrier concentration of a-ITZO was not affected by the heterostructure with Bi2Se3. In the case of the Bi2Se3 heterostructure, the carrier mobility and conductivity of a-ITZO were increased by 263.6% and 281.4%, respectively, whereas the resistivity of a-ITZO was reduced by 73.57%. This indicates that Bi2Se3 significantly improves the electrical properties of a-ITZO through its heterostructure, expanding its potential applications in electronic and thermoelectric devices.

A branched 2-O sulfated 1,3-/1,4-galactoglucan from Antrodia cinnamomea exhibits moderate antiproliferative and anti-inflammatory activities.

A sulfated galactoglucan (3-SS) was discovered in Antrodia cinnamomea with antiproliferative and anti-inflammatory activities. Chemical identification of 3-SS resulted in the determination of a partial repeat unit as a 2-O sulfated 1,3-/1,4-linked galactoglucan with a two-residual 1,6-O-ß-Glc branch on the 3-O position of a Glc. by monosaccharide analysis and 1D and 2D NMR spectroscopy. The anti-inflammation effects of 3-SS on RAW264.7 macrophage cells, such as IL-6 inhibition, restoration of LPS-induced IκB protein degradation, and inhibited LPS-induced TGFRII protein degradation, were confirmed to occur via AKT, ERK1/2, and p-38. In addition, 3-SS impaired the proliferation of H1975 lung cancer cells through EGFR/ERK/slug signaling. This is the first finding of 2-O sulfated 1,3-/1,4-galactoglucan with 1,6-ß-Glc branches with dual functions of anti-inflammatory and antiproliferative activities.

Zinc oxide nanostructures enhanced photoluminescence by carbon-black nanoparticles in Moiré heterostructures.

ZnO/carbon-black heterostructures were synthesized using a sol-gel method and crystallized by annealing at 500 °C under 2 × 10-2 Torr for 10 min. The crystal structures and binding vibration modes were determined by XRD, HRTEM, and Raman spectrometry. Their surface morphologies were observed by FESEM. The Moiré pattern that is observed in the HRTEM images confirms that the carbon-black nanoparticles were covered by the ZnO crystals. Measurements of optical absorptance revealed that the optical band gap of the ZnO/carbon-black heterostructures increased from 2.33 to 2.98 eV as the carbon-black nanoparticle content increases from 0 to 8.33 × 10-3 mol owing to the Burstein-Moss effect. The photoluminescence intensities at the near-band edge and of the violet, and blue light were increased by factors about 68.3, 62.8, and 56.8, respectively, when the carbon-black contents is of the 2.03 × 10-3 mol. This work reveals that the proper carbon-black nanoparticle content involved increases the PL intensities of the ZnO crystals in the short wavelength regime, supporting their potential application in the light-emitting devices.