Entropy weight method (EWM) is a commonly used weighting method that measures value dispersion in decision-making. The greater the degree of dispersion, the greater the degree of differentiation, and more information can be derived. Meanwhile, higher weight should be given to the index, and vice versa. This study shows that the rationality of the EWM in decision-making is questionable. One example is water source site selection, which is generated by Monte Carlo Simulation. First, too many zero values result in the standardization result of the EWM being prone to distortion. Subsequently, this outcome will lead to immense index weight with low actual differentiation degree. Second, in multi-index decision-making involving classification, the classification degree can accurately reflect the information amount of the index. However, the EWM only considers the numerical discrimination degree of the index and ignores rank discrimination. These two shortcomings indicate that the EWM cannot correctly reflect the importance of the index weight, thus resulting in distorted decision-making results.

DNA flap endonuclease 1 (FEN1) plays critical roles in maintaining genome stability and integrity by participating in both DNA replication and repair. Suppression of FEN1 in cells leads to the retardation of DNA replication and accumulation of unrepaired DNA intermediates, resulting in DNA double strand breaks (DSBs) and apoptosis. Therefore, targeting FEN1 could serve as a potent strategy for cancer therapy. In this study, we demonstrated that FEN1 is overexpressed in breast cancers and is essential for rapid proliferation of cancer cells. We showed that manipulating FEN1 levels in cells alters the response of cancer cells to chemotherapeutic drugs. Furthermore, we identified a small molecular compound, SC13 that specifically inhibits FEN1 activity, thereby interfering with DNA replication and repair in vitro and in cells. SC13 suppresses cancer cell proliferation and induces chromosome instability and cytotoxicity in cells. Importantly, SC13 sensitizes cancer cells to DNA damage-inducing therapeutic modalities and impedes cancer progression in a mouse model. These findings could establish a paradigm for the treatment of breast cancer and other cancers as well.

New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized. The comprehensive understanding of the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC(50) values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC(50) values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC(50) value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.