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Multi-drug resistance (MDR) is one of the leading causes of the anticancer failures. Besides the blockage of the MDR pathways, the development of more potent drugs is with urgent needs, but has been postponed mainly due to an imbalance between safety and efficacy. The recent development of the bioorthogonal prodrug activation strategy has shown immense potential to balance safety and efficacy, while recent studies only focused on few drug entities such as doxorubicin and monomethyl auristatin E, leaving the vast collection of toxins undetermined. Here we have enumerated typical molecular entities ranging from food and drug administration (FDA) approved drugs to a heated antibody drug conjugates (ADC) warhead and a trichothecene toxin to demonstrate that the bioorthogonal caging and specific activation could serve as a general design to increase the therapeutic index of bioactive molecules. These prodrugs can be efficiently activated on-demand by the bioorthogonal activators whose distribution was regulated by the cancer cell specific enzymatic non-covalent synthesis of supramolecular self-assemblies. The prodrug activation not only enhanced the synergistic therapeutic effect within a broad range of dose ratios but also allowed the convenient switching of drug identities to successfully combat MDR tumor in vivo. In general, this strategy might serve as a general platform, which can be readily applicable to enlarge the therapeutic window for various bioactive molecules. We envision that the spatiotemporal controlled bioorthogonal prodrug activation would facilitate the discovery of anticancer drugs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study identified the prevalence of depression and tested the influence of acculturation and family dynamics on depressive symptoms, among a community sample of older Chinese Americans., Method: Data came from a survey of 385 Chinese Americans aged 55 and older (Mage = 72.4 years, SD = 8.7) living in a large metropolitan area in the American Southwest. The survey was administered in 2013 through face-to-face interviews. Depressive symptoms were assessed with the 12-item Center for Epidemiological Studies Depression scale., Results: Approximately 19.5% of the sample reported mild depressive symptoms and an additional 8.5% reported moderate depressive symptoms. Three-step hierarchical regression analyses indicated that smaller family support network size and more family conflict were risk factors for depressive symptoms. The effect of acculturation was not significantly associated with depressive symptoms after controlling for family dynamics., Discussion: Family support and conflict play a prominent role in explaining depressive symptoms among Chinese American older adults. The effect of acculturation is minimal when older adults have supportive families and good health. Interventions or services aimed at promoting family harmony for members of this population should be considered.