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The oscillation property (OP) is a fundamental and important qualitative property for the vibrations of single span one-dimensional continuums such as strings, bars, torsion bars, and Euler beams. Any properly discretized continuum model should keep the OP. In literatures, the OP of discrete beam models is discussed essentially by means of matrix factorization. The discussion is model-specific and boundary-conditionspecific. Besides, matrix factorization is difficult in handling finite element (FE) models of beams. In this paper, according to a sufficient condition for the OP, a new approach to discuss the property is proposed. The local criteria on discrete displacements rather than global matrix factorizations are given to verify the OP. Based on the proposed approach, known results such as the OP for the 2-node FE beams via the Heilinger-Reissener principle (HR-FE beams) as well as the 5-point finite difference (FD) beams are verified. New results on the OP for the 2-node PE-FE beams and the FE Timoshenko beams with small slenderness are given. Through a simple manipulation, the qualitative property of discrete multibearing beams can also be discussed by the proposed approach. [ABSTRACT FROM AUTHOR]

Jiyuan Oridonin A (JOA) is a naturally occurring ent -kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA , the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC 50 value of 0.39 ± 0.09 μM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12 -induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA , which would contribute to its further development as an antitumor agent. [Display omitted] • Two series of novel fluorescent derivatives of JOA were designed and evaluated for toxicity. • Compound B12 displayed the strongest inhibitory activity (IC 50 = 0.39 ± 0.09 μM) and selectivity against HGC-27 cells. • B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. • Primary mechanism study indicated that B12 -induced apoptosis was related to the mitochondrial pathway. [ABSTRACT FROM AUTHOR]

Two series of proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were identified. Compound A16 displayed the most potent inhibition against LNCaP and showed excellent AR degradation efficacy at 30 μM. [Display omitted] • Two series of novel PROTACs and androgen receptor degradation efficacy have been discovered. • The best compound A16 displayed excellent binding affinity and AR degradation activity. • Molecular docking analysis illustrates the possible dual mechanism actions of these compounds with AR and E3 ligase. As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR +) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs. [ABSTRACT FROM AUTHOR]

As our research focus on anticancer drugs, two series of novel derivatives of Flexicaulin A (FA), an ent -kaurene diterpene, condensation with amino acid trifluoroacetate were synthesized, and their anti-proliferative activity against four human cancer cell lines (TE-1, MCF-7, A549 and MGC-803) were evaluated. Compared with FA, the anticancer activity and solubility of most derivatives were significantly improved. Among them, compound 6d had the best activity, and its IC 50 value against Esophageal cancer cells (TE-1) was up to 0.75 μM. Subsequent cellular mechanism studies showed that compound 6d could inhibit the proliferation of cancer cells, the formation of cell colonies, and increase the level of ROS on TE-1 cells. In addition, 6d could up-regulate the expressions of SAPK/JNK pathway-associated proteins (p-ASK1, p-MKK4 and p-JNK) and pro-apoptotic proteins (Bak, Bad and Noxa), remarkably increase the ratio of Bax to Bcl-2 and activate Cleaved Caspase-3/9/PARP. These results indicate that compound 6d induces apoptosis through the ROS/JNK/Bcl-2 pathway and holds promising potential as an anti-proliferative agent. The schematic diagram shown the possible pathway for 6d induced apoptosis on TE-1 cells. Image 1 • Two series of novel derivatives of Flexicaulin A were discovered as potential anti-proliferative agent. • Most of the derivatives showed improved solubility and enhanced anti-proliferative activity. • Compound 6d exerted the best anti-proliferative activity against TE-1 cells. • Compound 6d could inhibit the formation of cell colonies and increase the level of ROS on TE-1 cells. • Compound 6d could induce cell apoptosis of TE-1 cells through the ROS/JNK/Bcl-2 pathway. [ABSTRACT FROM AUTHOR]