Several laboratories have reported that overexpression of the multidrug resistance (MDR) protein is associated with intracellular alkalinization, and several investigators have reported that cells induced to undergo programmed cell death (apoptosis) acidify quite significantly. Because it is difficult to fully explain the resistance to apoptosis-inducing chemotherapeutic drugs that is exhibited by MDR tumor cells solely via altered drug transport alone [Hoffman et al. (1996) J. Gen. Physiol. 108, 295-313], we have investigated whether overexpression of the hu MDR 1 protein alters progression of the apoptotic cascade. LR73 fibroblasts induced to undergo apoptosis either via treatment with the chemotherapeutic drug colchicine or by serum withdrawal exhibit cellular volume changes, intracellular acidification, nuclear condensation, and chromosomal digestion ("ladder formation"), characteristic of apoptosis, in a temporally well-defined pattern. However, multidrug resistant LR73/20E or LR73/27 hu MDR 1 transfectants recently created in our laboratory without selection on chemotherapeutic drug are significantly delayed in the onset of apoptosis as defined by the above criteria, regardless of whether apoptosis is induced by colchicine treatment or by serum withdrawal. Thus, the delay cannot simply be due to the well-known ability of MDR protein overexpression to lower chemotherapeutic drug accumulation in MDR cells. LR73/27V500 "selectants", exhibiting similar levels of MDR protein overexpression but higher multidrug resistance due to selection with the chemotherapeutic drug vincristine, exhibit a slightly longer delay in the progression of apoptosis. Normal apoptotic cascade kinetics are partially restored by pre-treatment of the MDR cells with the MDR protein inhibitor verapamil. Untransfected LR73 cells not expressing MDR protein but elevated in pHi via manipulation of CO2/HCO3- as described [Hoffman et al. (1996) J. Gen. Physiol. 108, 295-313] are inhibited in DNA ladder formation, similar to LR73/hu MDR 1 transfectants. These results uncover an additional mechanism whereby MDR protein overexpression may promote the survival of tumor cells and further support the notion that in some systems intracellular acidification may be either causal or permissive for proper progression of the apoptotic cascade.

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Hierarchical hollow microspheres with nickel sulfide (NiS) nanorods as the in situ formed building blocks have been fabricated via a novel precursor hydrothermal method in alkaline solution of Na 2 S. In addition, hierarchical hollow microspheres with NiS nanoparticles as the in situ formed building blocks have also been successfully controlled-synthesized through the adjustment of experimental parameters. The NiS powders have been characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, selected area electron diffraction and high-resolution transmission electron microscopy. The reported controlled experiments allow us to propose the formation mechanism of nanorod-based NiS hierarchical hollow spheres, which involves sulfuration of Ni(OH) 2 precursors and their sequential Ostwald ripening process. When the two kinds of NiS hierarchical hollow spheres prepared herein are used as cathode materials for lithium-ion batteries, nanorod-based hierarchical hollow microspheres exhibit enhanced electrochemical properties as compared with nanoparticle-based hierarchical hollow microspheres. Electrochemical measurements have also shown that the initial discharge capacity of nanorod-based hierarchical hollow microspheres is 587.8 mAh$g À1 , which is close to the theoretical capacity of NiS (590 mAh$g À1 ). The results described in the present work may open up another way for the design of novel nanostructured materials for various applications.

Iron nanoparticles are highly desirable for their potential applications in magnetic and catalytic industry. However, their shape-controlled fabrication is still an important challenge. Here we successfully synthesized icosahedral face-centered cubic (fcc) Fe nanoparticles with size of 5-13 nm by a specifically designed thermodynamic governed synthetic route, which is facile but highly efficient and reproducible. With the aberration-corrected transmission electron microscopy (TEM), the unique icosahedral structure's pseudo-2-fold, 3-fold, and pseudo-5-fold axes were directly observed for the first time and verified by computer simulation, which reveals that nanoparticles' orientations have a large impact on HRTEM images at ultrahigh resolution. It is expected that as-synthesized Fe nanoparticles with sharp corners and edges would be beneficial for tailoring chemical and physical properties at the nanoscale.