No abstract

Effective management of rainstorm risk is essential for reducing regional rainstorm disaster risks and losses. In this paper, we discussed the influencing factors of urban rainstorm disaster (URSD) risk from four aspects and then constructed the index system of URSD risk assessment which includes 16 influencing factors. Furtherly, important indexes were extracted as the input of deep belief nets (DBN) model after analyzing the types and risk characteristics of URSD. As well as a coupling risk assessment model of URSD based on random forest and deep belief nets (RF-DBN) was established due to the capacity of highdimensional data processing of RF and robustness of DBN. To test the validity of this risk assessment model, it was applied to evaluate the rainstorm disaster risk in 11 districts of Nanjing, China, from May to September during 2009 and 2017. Finally, the risk grade map of rainstorm disaster in Nanjing was drawn and the corresponding countermeasures for the regulation and control of URSD were put forward. The results show that the rainstorm risk in Nanjing is generally high during the period of rainy season and the risk of rainstorm disaster has egional features during the flood season.

Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non–small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial–mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance. We developed two novel series of CD73 antibody, Ab001/Ab002 and humanized version Hu001/Hu002, which demonstrated high CD73 binding affinity, potent enzyme inhibition, and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Hu001/Hu002 inhibited growth of RAS-mutant NSCLC tumors in mice via enhanced antibody-dependent cell-mediated cytotoxicity and multifaceted remodeling of the tumor immune environment, reflecting diminished levels of tumor-associated macrophages, myeloid-derived suppressor cells, and tumor vasculature. A novel MMAE-conjugated CD73-ADC (Hu001–MMAE) elicited potent cytotoxicity against CD73-high expressing tumor cells (IC50<0.1 nmol/L) and suppressed in vivo growth of multiple NSCLC and glioma tumors, including the RAS-mutant models [minimum effective dose <1 mg/kg]. Treatment with CD73–ADC triggered a robust intratumoral accumulation of proinflammatory macrophages and activated dendritic cells (DC), which were not observed with naked CD73 antibody or standard chemotherapy. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer.

Two new quinone enantiomers (−) and (+)-merrilliaquinone (1a, 1b) were isolated from Illicium merrillianum, 1b exhibited a selective cytotoxicity between human hepatoma cell lines and normal human hepatic cells, while 1a didn't have such activity.

We constructed a small library of indole terpenoid mimics using a hybridizing strategy to link various indole and α,β-unsaturated enone building blocks together. Prepared compounds were evaluated for the cytotoxicity against a panel of cancer cell lines. An indolyl ketone called JP18 was identified as a cell cycle regulator, and the underlying mechanism was investigated.