Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinum-based chemotherapy is as high as 80%, but in most advanced patients, final relapse and death are caused by acquired drug resistance. The development of resistance to therapy in ovarian cancer is a significant hindrance to therapeutic efficacy. The resistance of ovarian cancer cells to chemotherapeutic mechanisms is rather complex and includes multidrug resistance, DNA damage repair, cell metabolism, oxidative stress, cell cycle regulation, cancer stem cells, immunity, apoptotic pathways, autophagy and abnormal signaling pathways. The present review provided an update of recent developments in our understanding of the mechanisms of ovarian cancer platinum-based chemotherapy resistance, discussed current and emerging approaches for targeting these patients and presented challenges associated with these approaches, with a focus on development and overcoming resistance. Contents1. Introduction 2. Literature review methods 3. Molecular mechanisms of platinum-based chemotherapy resistance in ovarian cancer 4. Conclusions

Multidrug resistance (MDR) and adverse side effects are the major challenges facing cancer chemotherapy. Here, pH/protease dually responsive, sericin-coated mesoporous silica nanoparticles (SMSNs) for lysosomal delivery of doxorubicin (DOX) to overcome MDR and reduce systemic toxicity are reported. Sericin, a natural protein from silkworm cocoons, is coated onto MSNs as a gatekeeper via pH sensitive imine linkages. The sericin shell prevents the premature leakage of encapsulated DOX from MSNs in extracellular environment. Once reaching drugresistant tumors, sericin's cell-adhesive bioactivity enhances cellular uptake of SMSNs that are in turn transported into perinuclear lysosomes, thus avoiding drug efflux mediated by membrane-bound pumps. Lysosomal acidity triggers cleavage of pH sensitive linkage between sericin and MSNs concurrently with lysosomal proteases deconstructing sericin shell. This pH/protease dual responsiveness leads to DOX burst release into cell nuclei, inducing effective cell death, thus reversing MDR. These DOX-loaded SMSNs not only effectively kill drug-resistant cells in vitro, but also significantly reduce the growth of DOX-resistant MCF-7/ADR (breast cancer cells) tumor by 70% in a preclinical animal model without eliciting systemic toxicity frequently encountered in current clinical therapeutic formulations. Thus, the dually responsive SMSNs are an effective, lysosome-tropic, and bio-safe delivery system for chemotherapeutics for combating MDR.

The evolution of microbial community and the fate of ARGs along different full-scale wastewater treatment processes (i.e., Anaerobic-Anoxic-Oxic, Oxidation Ditch, and Cyclic Activated Sludge System) were investigated in this study. We found that the sludges of bioreactors treating similar influent showed the similar microbial communities, independent of the treatment technologies. The horizontal gene transfer (HGT) mainly occurred in aeration tank rather that anaerobic/anoxic tank. More co-occurrence of potential pathogens and ARGs was found in wastewater than in sludge. Microbial biomass was the key driver for the fate of ARGs in wastewater, while mobile genetic elements (MGEs) was the key factor for the fate of ARGs in sludge. Combination of wastewater characteristics, microbial diversity, microbial biomass, and MGEs contributed to the variation of ARGs. Finally, it was found that enhanced nutrients removal process and tertiary treatment would benefit ARGs removal.