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Lei Lyu,1,* Lu-qi Huang,2,* Tao Huang,1 Wei Xiang,1 Jing-dong Yuan,1 Chuan-hua Zhang1 1Department of Urology, Wuhan No 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Neurology, Wuhan No 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: Gambogic acid (GA) is the main active ingredient of resin gamboges and possesses anti-cancer activity toward various human cancer cells. However, clinical application of GA has been limited by its poor aqueous solubility and dose-limiting toxicities. Cell-penetrating peptides (CPPs) are widely used to deliver anti-cancer drugs into cancer cells and to enhance the water solubility of drugs.Purpose: The object of this study was to synthesize peptide-drug conjugates in which the cell-penetrating peptide TAT (trans-activator of transcription) was conjugated to GA and evaluated the anti-cancer activity of this GA-CPP conjugate (GA-TAT) in EJ bladder cancer cells.Methods: GA is built onto the TAT, and the GA-TAT conjugates are cleaved from the solid support and purified via HPLC. The equilibrium solubility of GA-TAT was measured using the shake-flask method. The effects of GA-TAT on EJ cell viability and proliferation were determined by MTT assay, Edu assay and colony formation assay, respectively. After treated with 1.0 μM GA-TAT for 24 h, the apoptosis rate of EJ cells were detected by Acridine orange/ethidium bromide (AO/EB) assay and flow cytometry assay. The proteins of caspase-3 (processing), caspase-9 (processing), Bcl-2 and Bax were analyzed by Western blotting, and the intracellular reactive oxygen species (ROS) production was evaluated by a reactive oxygen species assay.Results: In contrast to free GA, the solubility of GA-TAT in water was significantly improved. Meanwhile, GA-TAT significantly

This monograph provides an analysis of the People's Republic of China's evaluation of multilateralism and its place in Chinese foreign relations in the Asia-Pacific region. In contrast to conventional scholarly wisdom, the author, Dr. Jing-dong Yuan, contends that China is not opposed to multilateral approaches. In fact, Dr. Yuan asserts that China has adopted an approach he dubs "conditional multilateralism." According to Dr. Yuan, China now recognizes that multilateral engagement is unavoidable and indeed can be useful in advancing China's interests. China's embrace of multilateralism, however, varies depending upon the particular forum and specific issue. Furthermore, Dr. Yuan contends China remains leery of entering into arrangements that might constrain its independence and flexibility. This change in China's attitude toward multilateralism is a significant one that has important implications for U.S. national security strategy and for U.S. interests in the Asia-Pacific. The Strategic Studies Institute is pleased to offer this study as a contribution to ongoing analyses and debates over the future roles China will play in the international security environment.