Temperature is an environmental driver of the COVID-19 outbreak in China. • The incidence of COVID-19 decreases with the increase of temperature. • A modified susceptible-exposedinfectious-recovered model was developed.
The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.
Enzymatic catalysis in living cells enables the in-situ detection of cellular metabolites in single cells, which could contribute to early diagnosis of diseases. In this study, enzyme is packaged in amorphous metal-organic frameworks (MOFs) via a one-pot co-precipitation process under ambient conditions, exhibiting 5–20 times higher apparent activity than when the enzyme is encapsulated in corresponding crystalline MOFs. Molecular simulation and cryo-electron tomography (Cryo-ET) combined with other techniques demonstrate that the mesopores generated in this disordered and fuzzy structure endow the packaged enzyme with high enzyme activity. The highly active glucose oxidase delivered by the amorphous MOF nanoparticles allows the noninvasive and facile measurement of glucose in single living cells, which can be used to distinguish between cancerous and normal cells.
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