Kinetic investigations of nonlinear electrostatic excitations in quantum plasmas.

For plasmas in an extremely high-density state, like stellar cores or compressed fuel in inertial fusion facilities, their behavior turns out to be quite different when compared with those plasmas in interstellar space or magnetic confinement devices. To figure out those differences and uncover the kinetic physics in electrostatic excitations, a quantum kinetic code solving Wigner-Poisson equations has been developed. Basic plasmon decay, Landau damping, and two-stream instability of extremely high-density plasmas are investigated by using our newly developed code. Numerical simulations show that in the linear region, the dispersion relations of intrinsic modes can be significantly affected by quantum effects, and such simulation results can be well described by the existing analytical theory. Especially in the nonlinear region, since the space-time scale of collective modes of plasmas is comparable to the electron de Broglie wavelength, their couplings produce some new physics: the energy exchange between the electron and the collective mode results in an abnormal oscillation that does not exist in classical plasmas.

Kinetic studies of exchange-correlation effect on the collective excitations of warm dense plasmas.

The exchange-correlation of electrons, as a fundamental effect in quantum mechanics, plays an important role in the collective motions of electrons in warm dense matter. We derive the quantum kinetic equations based on the time-dependent Kohn-Sham equation. By using a temperature-dependent functional for the exchange correlation, the excitations of electrostatic waves are analyzed under the adiabatic local density approximation (ALDA). We find that the influences of the exchange-correlation effect on the group velocity of electrostatic waves can be as high as 10% when both the density and temperature are low. Moreover, we also compare the results obtained by using ALDA-based kinetic theory, exchange kinetic theory, and quantum hydrodynamics, and discuss the differences among them.

Kinetic study of quantum two-stream instability by Wigner approach.

Classical plasma are typically of low density and/or high temperature. Two of its basic properties are Landau damping and two-stream instabilities. When increasing the plasma density, quantum effects appear and beam-plasma interactions show behavior different from the classical cases. We revisit Landau damping and two-stream instabilities under conditions when quantum hydrodynamic and quantum kinetic theory can be applied, the latter accounting for wave-particle interactions. We find that the instability growth rate behaves as pure two-stream instability without Landau damping when the countering stream velocity exceeds a certain threshold, which differs from the classical case.

Synthesis and in vitro and in vivo biological evaluation of novel derivatives of flexicaulin A as antiproliferative agents.

As our research focuses on anticancer drugs, a series of novel derivatives of flexicaulin A (FA), an ent-kaurene diterpene, condensed with an aromatic ring were synthesized, and their antiproliferative activities against four human cancer cell lines (TE-1, EC109, MCF-7, and MGC-803) were evaluated. The activities of most of the new compounds were better than those of FA. Compound 2y exhibited the best activity with an IC50 value reaching 0.13 µM against oesophageal cancer cells (EC109 cells). The IC50 values for 2y in normal cells (GES-1 cells and HUVECs) were 0.52 µM and 0.49 µM, respectively. Subsequent mechanistic investigations found that compound 2y can inhibit the proliferation of cancer cells and cell cloning. In addition, 2y could reduce the mitochondrial membrane potential, increase the apoptosis rate, and increase the ROS level in EC109 cells. Moreover, 2y can upregulate the expression of ROS/JNK pathway-related proteins (p-ASK1, p-MKK4, p-JNK, and p-Cjun (ser63)) and pro-apoptotic proteins (Bax, Bad, and Bim). In vivo experiments showed that 2y can inhibit tumour growth in nude mice. The mechanism involves an increase in protein expression in the ROS pathway, leading to changes in apoptosis-related proteins. In addition, compound 2y shows low toxicity. These results indicate that compound 2y holds promising potential as an antiproliferative agent.

The design, synthesis and anti-tumor mechanism study of new androgen receptor degrader.

Targeted protein degradation using small molecules is a novel strategy for drug development. In order to solve the problem of drug resistance in the treatment of prostate cancer, proteolysis-targeting chimeras (PROTAC) was introduced into the design of anti-prostate cancer derivatives. In this work, we synthesized two series of selective androgen receptor degraders (SARDs) containing the hydrophobic degrons with different linker, and then investigated the structure-activity relationships of these hybrid compounds. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Among them, compound A9 displayed potent inhibitory activity against LNCaP prostate cancer cell line with IC50 values of 1.75 µM, as well as excellent AR degradation activity. Primary mechanism studies elucidated compound A9 arrested cell cycle at G0/G1 phase and induced a mild apoptotic response in LNCaP cells. Further study indicated that the degradation of AR was mediated through proteasome-mediated process. For all these reasons, compound A9 held promising potential as anti-proliferative agent for the development of highly efficient SARDs for drug-resistance prostate cancer therapies.

Synthesis and in vitro biological evaluation of novel derivatives of Flexicaulin A condensation with amino acid trifluoroacetate.

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 IC50 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.

Synthesis and biological evaluation of novel Jiyuan Oridonin A-1,2,3-triazole-azole derivatives as antiproliferative agents.

As a continuation of our research on developing potent and potentially safe anti-proliferative agents, two series of novel Jiyuan Oridonin A-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their anti-proliferative activity against four selected cancer cell lines (MGC-803, MCF-7, PC-3, Eca-109). Some compounds with better growth inhibitory effects were chosen to carry out further studies in A549 and SMMC-7721. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, the most active agent 8b showed high potency against human cancer cells with IC50 ranging from 0.2 ±â€¯0.0 to 5.0 ±â€¯0.9 µM. Cellular mechanism studies elucidated compound 8b arrests cell cycle at G1 phase and induce a strong apoptotic response in SMMC-7721 cells. Furthermore, 8b could inhibit the colony formation and migration via Wnt signaling pathway in SMMC-7721 cells. For all these reasons, compound 8b holds promising potential as anti-proliferative agent.