Discovery of cyanoguanidine derivatives as biased μ-opioid receptor agonists.

Opioid agonists, including morphine and its derivatives, have historically been utilized in conventional pain relief therapies. However, the morphine-like side effects associated with these compounds have constrained their broader application in clinical environments. Fortunately, novel compounds that selectively activate μ-opioid receptors (MOR) without activating the β-arrestin2 pathway, such as PZM21 and TRV130, demonstrate the potential to mitigate side effects while maintaining analgesic efficacy.

Design, synthesis and mechanism studies of novel dual PARP1/BRD4 inhibitors against pancreatic cancer.

Inducing the deficiency of homologous recombination (HR) repair is an effective strategy to broaden the indication of PARP inhibitors in pancreatic cancer treatment. Repression of BRD4 has been reported to significantly elevate HR deficiency and sensitize cancer cells to PARP1/2 inhibitors. Inspired by the concept of synthetic lethality, we designed, synthetized and optimized a dual PARP1/BRD4 inhibitor III-7, with a completely new structure and high selectivity against both targets.

FDI-6 inhibits the expression and function of FOXM1 to sensitize BRCA-proficient triple-negative breast cancer cells to Olaparib by regulating cell cycle progression and DNA damage repair.

Inducing homologous-recombination (HR) deficiency is an effective strategy to broaden the indications of PARP inhibitors in the treatment of triple-negative breast cancer (TNBC). Herein, we find that repression of the oncogenic transcription factor FOXM1 using FOXM1 shRNA or FOXM1 inhibitor FDI-6 can sensitize BRCA-proficient TNBC to PARP inhibitor Olaparib in vitro and in vivo. Mechanistic studies show that Olaparib causes adaptive resistance by arresting the cell cycle at S and G/M phases for HR repair, increasing the expression of CDK6, CCND1, CDK1, CCNA1, CCNB1, and CDC25B to promote cell cycle progression, and inducing the overexpression of FOXM1, PARP1/2, BRCA1/2, and Rad51 to activate precise repair of damaged DNA.

Discovery of Potent and Novel Dual PARP/BRD4 Inhibitors for Efficient Treatment of Pancreatic Cancer.

Targeting poly(ADP-ribose) polymerase1/2 (PARP1/2) is a promising strategy for the treatment of pancreatic cancer with breast cancer susceptibility gene (BRCA) mutation. Inducing the deficiency of homologous recombination (HR) repair is an effective way to broaden the indication of PARP1/2 inhibitor for more patients with pancreatic cancer. Bromodomain-containing protein 4 (BRD4) repression has been reported to elevate HR deficiency.

Discovery of novel limonin derivatives as potent anti-inflammatory and analgesic agents.

Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds.

[Study on the damage of SiO2 thin films on LiNbO3 crystal in optical parametric oscillator by XRD spectrometry].

In an attempt to elucidate the damage in high transmission thin films on LiNbO3 crystal in optical parametric oscillator, the authors employed XRD spectrometry to investigate the spectrum of laser-induced damage in thin film as well as the morphology of the damage. The authors observed that the damage of thin film was characterized by the depressions/craters in the surface of the films, which were surrounded by a deposition layer with the deceasing thickness from the center of the craters. The XRD measurements indicate that the film was crystallized.

Terawatt femtosecond laser storage cavity with cholesteric liquid crystals for an x-ray source based on Compton scattering.

In laser Compton scattering systems, the limitation to higher average brightness is the low repetition rate of high-power lasers. We propose and demonstrate for the first time, as far as we know, a simple method by which x-ray yield could be enhanced nearly 2 orders of magnitude per second. The method, utilizing cholesteric liquid crystals as the entrance mirror of the laser storage cavity, can be used not only for storing femtosecond laser pulses with a peak power of several terawatts, but also to make high coupling efficiency and energy utilization efficiency accessible.

[The study on supercontinuum generation of femtosecond pulse propagating in fused silica].

Starting from Nonlinear Schrodinger's equation and using the split-step Fourier method, the authors studied the characters of the supercontinuum generation of femtosecond laser pulse propagating in fused silica, and many physical factors were included such as propagation distance, input pulse peak power, diffraction effect, dispersion effect andnonlinear effect etc. The results show that when the femtosecond pulse propagated inside the fused silica, the process of supercontinuum generation could be divided into two main stages: the pulse compression stage, which was induced by the self-focus and other third nonlinear effects of the fused silica; and the pulse split stage, which was caused by the self-phase modulation and the group velocity dispersion of the fused silica. When the femtosecond pulse propagated inside the fused silica with high input peak power, the 3rd-order nonlinear effect of material induced pulse compression and then the subpulses were produced, so that new frequency components were introduced.

[Study of supercontinuum in nanofiber].

Using split-step Fourier transform method, the authors performed the simulation on supercontinuum generation (SCG) of femtosecond laser in nanofiber. The effects of diameter of the nanofiber, peak power and input pulse duration on the supercontinuum generation were analyzed. The results show that the higher the peak power of the input pulse, the easier the supercontinuum generation could be observed; the narrower the input pulse, the wider the light spectrum width.