Enzalutamide Sensitizes Castration-Resistant Prostate Cancer to Copper-Mediated Cell Death.

Despite the initial efficacy of enzalutamide in castration-resistant prostate cancer (CRPC), inevitable resistance remains a significant challenge. Here, the synergistic induction of copper-dependent cell death (cuproptosis) in CRPC cells is reported by enzalutamide and copper ionophores (elesclomol/disulfiram). Mechanistically, enzalutamide treatment increases mitochondrial dependence in CRPC cells, rendering them susceptible to cuproptosis, as evidenced by specific reversal with the copper chelator tetrathiomolybdate. This susceptibility is characterized by hallmarks of cuproptosis, including lipoylated protein aggregation and iron-sulfur cluster protein instability. Interestingly, the mitochondrial matrix reductase, FDX1, specifically correlates with elesclomol sensitivity, suggesting a potential mechanistic divergence between the two copper ionophores. Notably, this synergistic effect extends beyond in vitro models, demonstrating efficacy in 22Rv1 xenografts, mouse Pten p53 knockout organoids. Importantly, enzalutamide significantly enhances copper ionophore-mediated cytotoxicity in enzalutamide-resistant cells. Collectively, these findings indicate that enzalutamide and copper ionophores synergistically induce cuproptosis, offering a promising therapeutic avenue for CRPC, potentially including enzalutamide-resistant cases.

A meta-analysis of postoperative wound complications at the surgical site in prostate cancer patients undergoing robotic surgery.

This meta-analysis critically evaluates the role of robotic surgery in reducing postoperative wound complications in prostate cancer patients, comparing it with traditional open and laparoscopic approaches. Our extensive literature search resulted in 9 studies comprising 2063 patients. The results highlighted a significant reduction in the incidence of wound complications, with an 84% heterogeneity index and a standardized mean difference (SMD) of 0.49 (95% Confidence Intervals: 0.42 to 0.58, p < 0.01) in favour of robotic surgery. Additionally, a notable decrease in wound infection rates was observed, marked by a 94% heterogeneity index and a SMD of 0.26 (95% CIs: 0.19 to 0.35, p < 0.01). A considerable reduction in wound dehiscence events was also noted, particularly in a subset of studies, reflecting a 70% heterogeneity index and a SMD of 0.23 (95% CIs: 0.12 to 0.45, p < 0.01). These findings suggest that robotic surgery may offer significant advantages in managing wound-related outcomes in prostate cancer surgeries. However, the variability among the studies warrants cautious interpretation of the results and underscores the need for more targeted research in this area.

Differences in selenium concentration and bioavailability between paddy and dryland soils of China: A study based on literature collection and field sampling.

Lack systematic understanding of differences in environmental behavior of selenium between paddy and dryland soils affects Se biofortification and leads to human Se-related health risks. Therefore, this study investigated differences in Se concentration and bioavailability between paddy and dryland soils using data collected from literatures and field sampling. Our analysis showed paddy soil Se concentration in Se-rich area of China was significantly lower than that in dryland soil. Selenium biological concentration factor of rice grain (BCFgrain) in Se-rich area was lower than that in non-Se-rich area attributed to higher percentage of selenite in available Se. Concentration and percentage of available Se were in dryland soil lower than those in paddy soil and this affected BCFgrain of maize, whereas BCFgrain of rice was further influenced by its Se transport capacity. The ranges of Se concentration in Se-rich paddy (0.14-3.63 mg kg-1) and dryland (0.45-1.17 mg kg-1) soils were derived using a linear regression model. The current soil Se concentration evaluation standard was only suitable for dryland but overestimated Se-deficiency and Se-toxicity levels in paddy field. The present study provides theoretical foundations for understanding Se concentrations and bioavailability in soils and selecting efficient and safe approach on cultivated land use.

Electrochemical immunosensor based on hyperbranched structure for carcinoembryonic antigen detection.

Sensitive determination of carcinoembryonic antigen (CEA) is very important in clinical research and diagnosis. Herein we report the design and synthesis of a new kind of immunosensor based on the benefits of hyperbranched structure. The hyperbranched polyester was grafted to the surface of indium tin oxides glass (ITO) electrode, and the grafting processes were characterized by attentuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). After CEA and horse radish peroxidase (HRP)-labeled antibody-conjugated AuNPs (HRP-Ab2-AuNPs) bioconjugates were immobilized on the surface of the hyperbranched structure-modified electrode, the optimized conditions of the above electrode were investigated. Moreover, the analytical performance of the proposed immunosensor showed a high sensitivity, a linear range from 0.01 to 80ng/mL with a low detection limit of 2.36pg/mL, and good selectivity for CEA. The designed immunoassay system holds great potential for ultrasensitive electrochemical biosensing of other analytes.

Preparation of hemocompatible cellulosic paper based on P(DMAPS)-functionalized surface.

The surface-modification of paper substrates with functional layers is gaining increasing interest, both from academic and industrial research. In this case, the cellulosic paper (CP) surface was functionalized with zwitterionic poly-(3-dimethyl(methacryloyloxyethyl) ammoniumpropane sulfonate) (CP-g-P(DMAPS) via surface-initiated atom transfer radical polymerization (ATRP) technique for enhancing blood compatibility. An obvious increase in graft yield of the functional P(DMAPS) with polymerization time was observed. The new CP-g-P(DMAPS) produced was investigated for its hemocompatibility. The hemocompatibility studied including platelet and whole blood ceels adhesion tests, hemolysis assay, morphological changes of red blood cells (RBCs), coagulation time tests, and complement activation, platelet activation at the molecular level. Most assays had remarkable differences in the presence of the new zwitterionic CP, indicated the importance of the zwitterion for hemocompatibility of CP.

Fabrication of nonbiofouling metal stent and in vitro studies on its hemocompatibility.

In recent years, there has been increasing interest for the surface modification of biomaterials in order to improve their surface properties. The bare metal stents surface based on 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate polymers has shown an excellent antifouling and blood compatibility by using surface-initiated atom transfer radical polymerization. Surface structure, morphology, wettability, and element content were characterized by scanning electronic microscope, static water contact angles measurement, X-ray photoelectron spectroscopy measurement, respectively. The results showed zwitterionic brushes were successfully fabricated on bare metal stents. The blood compatibility of bare metal stents before and after modification was evaluated by platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, coagulation time tests, plasma recalcification time assay, complement activation, and platelet activation at molecular level. Moreover, the cytotoxicity was also to be characterized. All assays showed after the modification with zwitterionic brush the metal stents displayed a property of excellent blood compatibility and low cytotoxicity.