Luteolin induces ferroptosis in prostate cancer cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

BACKGROUND: As the second most common cancer in men and the leading cause of cancer-related death, prostate cancer (PCa) could potentially be treated by inducing ferroptosis. In this study, we aimed to investigate whether luteolin could induce ferroptosis in PCa cells through the transcription Factor EB (TFEB). METHODS: Different concentrations of luteolin were applied to treat normal prostate epithelial cells RWPE-1 and PCa cell lines DU145, PC-3, VCaP, and LNcaP. Ferrostatin-1 (Fer-1), Necrostain-1 (Nec-1), 3-methyladenine (3-MA), chloroquine (CQ), and the apoptosis inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK) were added to treat DU145 and PC-3 cells. Additionally, we knocked down TFEB and performed in vitro cell experiments. Finally, tumor-forming experiments in nude mice were conducted to verify luteolin mechanism in PCa after knocking down TFEB. RESULTS: There was no significant difference in RWPE-1 at 12, 24, and 48 h after treatment with 60 µM luteolin. However, a significant difference was observed between DU145 and PC-3 cells. Luteolin exhibited a promoting effect on PCa cell death. After treatment with luteolin, cell viability, and Ki67 expression were decreased, and AnV-PI-positive dead cells were increased. Fer-1, Nec-1, 3-MA, and Z-VAD-FMK reversed luteolin effects on DU145 and PC-3 cell viability, proliferation, and AnV-PI-positive dead cells. Among them, Fer-1 and 3-MA were more effective. Luteolin-induced increased autophagy and ferroptosis in DU145 and PC-3 cells. Moreover, luteolin promoted ferroptosis by inducing increased autophagy in DU145 and PC-3 cells. However, knockdown of TFEB reversed the ability of luteolin to induce lysosome degradation of ferritin. In addition, luteolin promoted PCa ferroptosis by inducing ferritinophagy in vivo. CONCLUSIONS: Luteolin-induced ferroptosis in PCa cells by promoting TFEB nuclear translocation and increasing ferritinophagy.

Quantized spiral-phase-modulation based deep learning for real-time defocusing distance prediction.

Whole slide imaging (WSI) has become an essential tool in pathological diagnosis, owing to its convenience on remote and collaborative review. However, how to bring the sample at the optimal position in the axial direction and image without defocusing artefacts is still a challenge, as traditional methods are either not universal or time-consuming. Until recently, deep learning has been shown to be effective in the autofocusing task in predicting defocusing distance. Here, we apply quantized spiral phase modulation on the Fourier domain of the captured images before feeding them into a light-weight neural network. It can significantly reduce the average predicting error to be lower than any previous work on an open dataset. Also, the high predicting speed strongly supports it can be applied on an edge device for real-time tasks with limited computational source and memory footprint.

Quercetin in Tonglong Qibi decoction ameliorates testosterone-induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress.

Benign prostatic hyperplasia (BPH) is a common urological disease in older males. Existing pharmacotherapy shows several side effects, and the exploration of new therapeutic strategies is of high significance. Tonglong Qibi (TQ) decoction was proved to ameliorate BPH, while the underlying mechanisms are still unclear. In the current study, we explored the anti-BPH effects of TQ in vivo and identified its main therapeutic component and the underlying mechanisms in vitro. We demonstrated that TQ mitigated BPH in rats and showed no toxicity to the liver and reproductive system. Network pharmacology identified quercetin as the main component in TQ treating BPH. Quercetin reduced proliferation, oxidative stress, and increased Nrf2 expression in hyperplastic prostate epithelial cells. These findings indicate that quercetin in TQ alleviates BPH via inhibiting oxidative stress and activating the Nrf2 signalling pathway.

Nonreciprocal parity-time phase in magnetized waveguides.

In a single magneto-optical (MO) waveguide, the dispersion of guided bulk wave is reciprocal in the Voigt configuration. Here we show that the parity-time (P T) phase in two coupled MO waveguides can be nonreciprocal if the waveguides are properly biased. The nonreciprocal P T phase is closely related to the asymmetric field profile induced by the MO effect that modifies the coupling strength between adjacent waveguides. We show that it is feasible to switch between broken and conserved P T phases by simply reversing the magnetic bias or the propagating direction of wave. Theoretical analysis and numerical calculation prove our theory. This investigation highlights a flexible method in manipulating the field dynamics of waveguide arrays by using the novel properties of P T phase especially the exceptional points.

Exceptional singular resonance in gain mediated metamaterials.

We study the scattering of optical field by a hybridized metamaterial with properly imprinted gain. We predict that an occasionally real-eigen valued singularity in the interaction matrix of the coupled dark-bright meta-molecule would produce a high-Q resonance. This effect is demonstrated in full-wave three-dimensional finite element optical simulation. Field is efficiently amplified at this resonance. Further investigation shows that the resonance is associated with an exceptional point. The difference of this exceptional singularity from other high-Q resonances such as the spectral singularities in the scattering or transfer matrixes of parity-time symmetric systems and the bound states in the continuum is discussed. The non-Hermitian nature of the exceptional singularity promises some nonlinear applications.

Parity-time symmetry in periodically curved optical waveguides.

The coupling strength between two parity-time (PT) symmetric resonators determines whether the PT phase is broken or not. Here we investigate the scenario that two optical waveguides are spatially curved so that they switch periodically between unbroken and broken PT phases. We show that the existence of locally broken PT phase does not necessarily render a broken phase to waves propagating inside. Criteria are proposed to characterize the collective dynamics of wave near the Brillouin zone (BZ) edge, toward the cases of a totally broken phase, a partially broken phase, or a totally unbroken phase. We also discuss the characteristics of two special kinds of exceptional points (EPs) at the BZ edge, and show that their field patterns are displaced by half a period with each other. Full-wave numerical simulation proves our analysis. Potential applications especially these associated with EPs are discussed. This study helps us to understand how the locally PT-symmetric related eigenstate influences the globally collective dynamics of wave in spatially periodic configuration.