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Regulating nonlinear optical (NLO) property of metal−organic frameworks (MOFs) is of pronounced significance for their scientific research and practical application, but the regulation through external stimuli is still a challenging task. Here we prepare and electrically control the nonlinear optical regulation of conductive MOFs Cu-HHTP films with [001]- (Cu-HHTP [001] ) and [100]-orientations (Cu-HHTP [100] ). Z-scan results show that the nonlinear absorption coefficient ( β ) of Cu-HHTP [001] film (7.60 × 10 −6  m/W) is much higher than that of Cu-HHTP [100] film (0.84 × 10 −6  m/W) at 0 V and the β of Cu-HHTP [001] and Cu-HHTP [100] films gradually increase to 3.84 × 10 −5 and 1.71 × 10 −6  m/W at 10 V by increasing the applied voltage, respectively. Due to 2D Cu-HHTP having anisotropy of charge transfer in different orientations, the NLO of MOFs film can be dependent on their growth orientations and improved by tuning the electrical field. This study provides more avenues for the regulation and NLO applications of MOFs. Nonlinear optical properties of metal-organic framework can be tuned for potential optical applications. Here the authors demonstrate an enhancement the nonlinear absorption coefficient of MOF film by applying external electric field.

Induced protein degradation has emerged as an innovative drug discovery approach, complementary to the classical method of suppressing protein function. The androgen receptor signaling pathway has been identified as the primary driving force in the development and progression of lethal castration-resistant prostate cancer. Since androgen receptor degraders function differently from androgen receptor antagonists, they hold the promise to overcome the drug resistance challenges faced by current therapeutics. Proteolysis-targeting chimeras (PROTACs), monomeric degraders, hydrophobic tagging, molecular glues, and autophagic degradation have demonstrated their capability in downregulating intracellular androgen receptor concentrations. The potential of these androgen receptor degraders to treat castration-resistant prostate cancer is substantiated by the advancement of six PROTACs and two monomeric androgen receptor degraders into phase I or II clinical trials. Although the chemical structures, in vitro and in vivo data, and degradation mechanisms of androgen receptor degraders have been reviewed, it is crucial to stay updated on recent advances in this field as novel androgen receptor degraders and new strategies continue to emerge. This review thus provides insight into recent advancements in this paradigm, offering an overview of the progress made since 2020.

A variety of microtubule-stabilizing cytotoxic agents (MSA) with diverse chemical scaffolds have been discovered from marine sponges, microorganisms, and plants. Two MSAs, docetaxel and cabazitaxel, are the exclusive chemotherapeutics that convey a survival benefit in patients with castration-resistant prostate cancer (CRPC). Additional MSAs have been investigated for their potential in treating prostate cancer in both clinical and preclinical settings. Independent of promoting mitotic arrest, MSAs can suppress the nuclear accumulation of androgen receptor (AR), which is the driving force for prostate cancer cell growth and progression. The alternative mechanism not only helps to better understand the clinical efficacy of docetaxel and cabazitaxel for AR-driven CRPC but also provides an avenue to seek better treatments for various forms of prostate cancer. The dual mechanisms of action enable MSAs to suppress AR-null prostate cancer cell proliferation by cell mitosis pathway and to interfere with the AR signaling pathway in AR positive cells. MSA chemotherapeutics, being administered alone or in combination with other therapeutics, may serve as the optimal therapeutic option for patients with either castration-sensitive or castration-resistant prostate cancer. This review provides an overview of the anti-prostate cancer profiles (including preclinical and clinical studies, and clinical use) of diverse MSAs, as well as the mechanism of action.

Enzalutamide is the first second-generation nonsteroidal androgen receptor (AR) antagonist with a strong binding affinity to AR. Most significantly, enzalutamide can prolong not only overall survival time and metastatic free survival time for patients with lethal castration-resistant prostate cancer (CRPC), but also castration-resistant free survival time for patients with castration-sensitive prostate cancer (CSPC). Enzalutamide has thus been approved by the US Food and Drug Administration (FDA) for the treatment of both metastatic (in 2012) and non-metastatic (in 2018) CRPC, as well as CSPC (2019). This is an inspiring drug discovery story created by an amazing interdisciplinary collaboration. Equally important, the successful clinical use of enzalutamide proves the notion that the second-generation AR antagonists can serve as hormonal therapeutics for three forms of advanced prostate cancer. This has been further verified by the recent FDA approval of the other two second-generation AR antagonists, apalutamide and darolutamide, for the treatment of prostate cancer. This review focuses on the rational design and discovery of these three second-generation AR antagonists, and then highlights their syntheses, clinical studies, and use. Strategies to overcome the resistance to the second-generation AR antagonists are also reviewed.

Melatonin ( -acetyl-5-methoxytryptamine) plays important role in multiple plant developmental processes and stress responses. We investigated the possible mediatory role of melatonin in growth, photosynthesis, and the response to cold stress in rice by using three different experiments: soaking seed; immersing roots, and spraying to leaves with 0, 20, or 100 μM melatonin. After 6 days of cold stress, the growth of rice seedlings was significantly inhibited, but this inhibition was alleviated by exogenous melatonin. Furthermore, exogenous melatonin pretreatment alleviated the accumulation of reactive oxygen species, malondialdehyde and cell death induced by cold stress. Melatonin pretreatment also relieved the stress-induced inhibitions to photosynthesis and photosystem II activities. Further investigations showed that, antioxidant enzyme activities and non-enzymatic antioxidant levels were increased by melatonin pretreatments. The treatment methods of seed soaking and root immersion were more effective in improving cold stress resistance than the spraying method. The results also indicated the dose-dependent response of melatonin on rice physiological, biochemical, and photosynthetic parameters.

For the intelligence of metamaterials, the -sensing mechanism and programmable reaction units are two important components for self-recognition and -determination. However, their realization still face great challenges. Here, we propose a smart sensing metasurface to achieve self-defined functions in the framework of digital coding metamaterials. A sensing unit that can simultaneously process the sensing channel and realize phase-programmable capability is designed by integrating radio frequency (RF) power detector and PIN diodes. Four sensing units distributed on the metasurface aperture can detect the microwave incidences in the - and -polarizations, while the other elements can modulate the reflected phase patterns under the control of a field programmable gate array (FPGA). To validate the performance, three schemes containing six coding patterns are presented and simulated, after which two of them are measured, showing good agreements with designs. We envision that this work may motivate studies on smart metamaterials with high-level recognition and manipulation.

Prostate cancer remains a significant global health concern, prompting ongoing exploration of novel therapeutic agents. Licochalcone A, a natural product in the chalcone family isolated from licorice root, is characterized by its enone structure and demonstrates antiproliferative activity in the micromolar range across various cell lines, including prostate cancer. Building on our prior success in enhancing curcumin’s antiproliferative potency by replacing the substituted phenol with a 1-alkyl-1H-imizadol-2-yl moiety, we applied a similar approach to design a new class of licochalcone A-inspired chalcones. The synthesis of these target chalcones involved key [3,3]-sigmatropic rearrangement of aryl prenyl ethers and Claisen–Schmidt condensations, yielding three derivative series. These compounds were evaluated for antiproliferative activity in both androgen receptor (AR)-positive and AR-null prostate cancer cell models using WST-1 cell proliferation assay. Systematic evaluation of licochalcone A across four prostate cancer cell lines indicated a modest advantage over enzalutamide, an FDA-approved AR antagonist, in suppressing 22Rv1 cell proliferation. Interestingly, three ester derivatives by replacing the phenol next to the carbonyl with an alkoxide demonstrated similar antiproliferative potency to licochalcone A in both AR-positive and AR-negative prostate cancer cell lines. This suggests that the phenol moiety on licochalcone A may be a promising site for chemical manipulations to enhance anti-prostate cancer activity. Among the synthesized chalcones, nine derivatives showed improved selectivity for AR-positive LNCaP and 22RV1 cells relative to AR-negative PC-3 and DU145 cells, surpassing licochalcone A in selectivity. Additionally, the antiproliferative potency was highly dependent on the R group attached to the imidazole. Most of the derivatives showed antiproliferative potency against androgen receptor-positive LNCaP and 22Rv1 cells, comparable to that of enzalutamide and licochalcone A. These findings suggest that optimization of licochalcone A-inspired chalcones as potential anti-prostate cancer agents warrants further investigation.

In order to obtain high-quality kiwifruits with health-promoting characteristics, physicochemical properties, phenolic profiles, antioxidant capacities, and inhibitory effects on digestive enzymes (pancreatic lipase and α-glucosidase), of fourteen different types of kiwifruit obtained from China were systematically investigated and compared. Noticeable variations in the fruits’ physicochemical properties and phenolic profiles were observed among them. The total phenolic content of Actinidia chinensis cv. Hongshi, A. chinensis cv. Jinshi, and A. chinensis cv. Jinlong were 16.52 ± 0.26 mg GAE/g DW (dry weight), 13.38 ± 0.20 mg GAE/g DW, and 11.02 ± 0.05 mg GAE/g DW, respectively, which were much higher than those of the other tested kiwifruits. According to high performance liquid chromatography (HPLC) analysis, phenolic compounds, including procyanidin B1, procyanidin B2, (−)-epicatechin, chlorogenic acid, gallic acid, and quercetin-3-rhamnoside, were found to be the major compounds in kiwifruits, while procyanidin B1, procyanidin B2, and chlorogenic acid were the most abundant phenolic compounds. Furthermore, all the tested kiwifruits exerted remarkable antioxidant capacities and inhibitory effects on pancreatic lipase and α-glucosidase. Indeed, A. chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong exhibited much better antioxidant capacities and inhibitory effects on digestive enzymes than those of the other tested kiwifruits. Particularly, A. polygama showed the highest inhibitory activity on α-glucosidase. Therefore, Actinidia chinensis cv. Hongshi, Actinidia chinensis cv. Jinshi, and Actinidia chinensis cv. Jinlong, as well as A. polygama could be important dietary sources of natural antioxidants and natural inhibitors against pancreatic lipase and α-glucosidase, which is helpful for meeting the growing demand for high-quality kiwifruits with health-promoting characteristics in China.

Screening ligands directly binding to an ensemble of intrinsically disordered proteins (IDP) to discover potential hits or leads for new drugs is an emerging but challenging area as IDPs lack well-defined and ordered 3D-protein structures. To explore a new IDP-based rational drug discovery strategy, a differential binding score (DIBS) is defined. The basis of DIBS is to quantitatively determine the binding preference of a ligand to an ensemble of conformations specified by IDP versus such preferences to an ensemble of random coil conformations of the same protein. Ensemble docking procedures performed on repeated sampling of conformations, and the results tested for statistical significance determine the preferential ligand binding sites of the IDP. The results of this approach closely reproduce the experimental data from recent literature on the binding of the ligand epigallocatechin gallate (EGCG) to the intrinsically disordered N -terminal domain of the tumor suppressor p53. Combining established approaches in developing a new method to screen ligands against IDPs could be valuable as a screening tool for IDP-based drug discovery.

Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential N-terminal AR antagonist, this study aims to explore the structure–activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation. Dehydroabietylamine, abietic acid, dehydroabietic acid, and their derivatives were selected, since they have a similar core structure as QW07. Twenty diterpenoids were prepared for the evaluation of their antiproliferative potency on AR-positive prostate cancer cell models (LNCaP and 22Rv1) using AR-null cell models (PC-3 and DU145) as comparisons. Our data indicated that six tricyclic diterpenoids possess greater potency than enzalutamide (FDA-approved AR antagonist) towards LNCaP and 22Rv1 AR-positive cells, and four diterpenoids are more potent than enzalutamide against 22Rv1 AR-positive cells. The optimal derivative possesses greater potency (IC50 = 0.27 µM) and selectivity than QW07 towards AR-positive 22Rv1 cells.