The precise molecular mechanism underlying arsenic trioxide (As 2 O 3 )-induced apoptosis is a subject of extensive study. Here, we show that clinically relevant doses of As 2 O 3 can induce typical apoptosis in IM-9, a multiple myeloma cell line, in a Bcl-2 inhibitable manner. We confirmed that As 2 O 3 directly induced cytochrome c (cyto c) release from isolated mouse liver mitochondria via the mitochondrial permeability transition pore, and we further identified the voltage-dependent anion channel (VDAC) as a biological target of As 2 O 3 responsible for eliciting cyto c release in apoptosis. First, pretreatment of the isolated mitochondria with an anti-VDAC antibody specifically prevented As 2 O 3 -induced cyto c release. Second, in proteoliposome experiments, VDAC by itself was sufficient to mediate As 2 O 3 -induced cyto c release, which could be specifically inhibited by Bcl-X L . Third, As 2 O 3 induced mitochondria membrane potential (DWm) reduction and cyto c release only in the VDAC-expressing, but not in the VDAC-deficient yeast strain. Finally, we found that As 2 O 3 induced the increased expression and homodimerization of VDAC in IM-9 cells, but not in Bcl-2 overexpressing cells, suggesting that VDAC homodimerization could potentially determine its gating capacity to cyto c, and Bcl-2 blockage of VDAC homodimerization represents a novel mechanism for its inhibition of apoptosis.

Mitochondria play central roles in cellular metabolism and apoptosis and are a major source of reactive oxygen species (ROS). We investigated the role of ROS and mitochondria in radiation-induced apoptosis in multiple myeloma cells. Two distinct levels of ROS were generated following irradiation: a small increase observed early, and a pronounced late increase, associated with depletion of reduced glutathione (GSH) and collapse of mitochondrial membrane potential (Dw m ). Exogenous ROS and caspase-3 induced Dw m drop and cytochrome c release from mitochondria, which could be prevented by molecular (dominant-negative caspase-9) and pharmacologic (zVAD-fmk) caspase inhibitors and overexpression of Bcl-2. Exogenous ROS also induced mitochondrial permeability transition (PT) pore opening and cytochrome c release in isolated mitochondria, which could be blocked by inhibition of PT with cyclosporin A. These results indicate that the late ROS production is associated with increased PT pore opening and decreased Dw m , and GSH, events associated with caspase activation and cytochrome c release.

The broad utility as an environmentally friendly and colorful coating of cellulose nanocrystal (CNC) was limited by its instability of coloration, brittleness, and lack of adhesion to a hydrophobic surface. In the present work, a neutral polymer, poly(ethylene glycol) (PEG) was introduced into CNC coatings through evaporation-induced self-assembly (EISA) on polymer matrices. The structure-color and mechanical properties of the composite coating or coating film were characterized by UV-vis spectroscopy, polarized light microscopy (PLM), scanning electron microscopy (SEM), wide-angle X-ray diffraction (WXRD), and tensile tests. Results showed that the reflective wavelength of the iridescent CNCs could be finely tuned by incorporation of PEG with varied loadings from 2.5 to 50 wt %, although the high loading content of PEG would produce some side effects because of the severe microphase separation. Second, PEG played an effective plasticizer to improve the ductility or flexibility of the CNC coating or coating film. Furthermore, as a compatibilizer, PEG could effectively and tremendously enhance the adhesion strength between CNCs and neutral polymer matrices without destroying the chiral nematic mesophases of CNCs. Environmentally friendly CNC/PEG composites with tunable iridescence, good flexibility, and high bonding strength to hydrophobic polymer matrices are expected to be promising candidates in the modern green paint industry.

A new Co(II)-based MOF, {[Co(tzpa)(OH)(HO)]·DMF} (1) (Htzpa = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid), was constructed by employing a tetrazolyl-carboxyl ligand Htzpa. 1 possesses 1D tubular channels that are decorated by μ-OH groups, uncoordinated carboxylate O atoms, and open metal centers generated by the removal of coordinated water molecules, leading to high CO adsorption capacity and significantly selective capture for CO over CH and CO in the temperature range of 298-333 K. Moreover, 1 shows the chemical stability in acidic and basic aqueous solutions. Grand canonical Monte Carlo simulations identified multiple CO-philic sites in 1. In addition, the activated 1 as the heterogeneous Lewis and Brønsted acid bifunctional catalyst facilitates the chemical fixation of CO coupling with epoxides into cyclic carbonates under ambient conditions.