Elucidating the Multimodal Anticancer Mechanism of an Organometallic Terpyridine Platinum(II) N-Heterocyclic Carbene Complex against Triple-Negative Breast Cancer In Vitro and In Vivo.

Treatment of triple-negative breast cancer (TNBC) has long been a medical challenge because of the lack of effective therapeutic targets. Targeting lipid, carbohydrate, and nucleotide metabolism pathways has recently been proven as a promising option in view of three heterogeneous metabolic-pathway-based TNBC subtypes. Here, we present a multimodal anticancer platinum(II) complex, named Pt(II)caffeine, with a novel mode of action involving simultaneous mitochondrial damage, inhibition of lipid, carbohydrate, and nucleotide metabolic pathways, and promotion of autophagy. All these biological processes eventually result in a strong suppression of TNBC MDA-MB-231 cell proliferation both in vitro and in vivo. The results indicate that Pt(II)caffeine, influencing cellular metabolism at multiple levels, is a metallodrug with increased potential to overcome the metabolic heterogeneity of TNBC.

Design, synthesis and biological evaluation of novel 4-aminopiperidine derivatives as SMO/ERK dual inhibitors.

The hedgehog (Hh) pathway is tightly related with the formation, metastasis and recurrence of various cancers, which makes it a perfect anticancer target. Smoothened (SMO) is one of its key members. Three drugs targeting the Hh pathway have been successfully used in clinic, and they are all known as SMO inhibitors. However, serious drug resistant problem has limited their clinical application. The interaction of oncogenic ERK pathway with the Hh pathway in multiple ways has been proved as one of the main factors that result in drug resistance. Dual inhibition of the Hh and ERK pathways has displayed synergistic suppression to cancer cells overexpressing both pathways. Herein, we designed and synthesized a series of novel 4-aminopiperidine derivatives as SMO/ERK dual inhibitors, and evaluated their biological activities. The results showed that compounds I-13 displayed strong inhibitory activities towards both SMO and ERK, and it also exhibited significant cytotoxicity against human cholangiocarcinoma RBE cells which overexpress both the Hh and ERK pathways. All the results indicate that compound I-13 is a promising anticancer candidate as a SMO/ERK dual inhibitor.

Simulation of crop growth, time to maturity and yield by an improved sigmoidal model.

Models that accurately estimate maximum crop biomass to obtain a reliable forecast of yield are useful in crop improvement programs and aiding establishment of government policies, including those addressing issues of food security. Here, we present a new sigmoidal growth model (NSG) and compare its performance with the beta sigmoidal growth model (BSG) for capturing the growth trajectories of eight crop species. Results indicated that both the NSG and the BSG fitted all the growth datasets well (R2 > 0.98). However, the NSG performed better than the BSG based on the calculated value of Akaike's information criterion (AIC). The NSG provided a consistent estimate for when maximum biomass occurred; this suggests that the parameters of the BSG may have less biological importance as compared to those in the NSG. In summary, the new sigmoidal growth model is superior to the beta sigmoidal growth model, which can be applied to capture the growth trajectory of various plant species regardless of the initial biomass values at the beginning of a growth period. Findings of this study will be helpful to understand the growth trajectory of different plant species regardless of their initial biomass values at the beginning of a growth period.