An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer

Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insufficiency of ADT over time leads to castration-resistant PCa (CRPC) in which the AR axis is still active, despite castrate levels of circulating androgens. Despite the approval and use of multiple generations of competitive AR antagonists (antiandrogens), antiandrogen resistance emerges rapidly in CRPC due to several mechanisms, mostly converging in the AR axis. Recent evidence from multiple groups have defined noncompetitive or noncanonical direct binding sites on AR that can be targeted to inhibit the AR axis. This review discusses new developments in the PCa treatment paradigm that includes the next-generation molecules to noncanonical sites, proteolysis targeting chimera (PROTAC), or noncanonical N-terminal domain (NTD)-binding of selective AR degraders (SARDs). A few lead compounds targeting each of these novel noncanonical sites or with SARD activity are discussed. Many of these ligands are still in preclinical development, and a few early clinical leads have emerged, but successful late-stage clinical data are still lacking. The breadth and diversity of targets provide hope that optimized noncanonical inhibitors and/or SARDs will be able to overcome antiandrogen-resistant CRPC.     

Maintenance of postharvest quality and bioactive compounds of fresh‐cut sweet leaf bush (Sauropus androgynus L. Merr.) through hot CaCl2 dips

The effects of hot CaCl₂ dips on postharvest quality and bioactive compounds of fresh‐cut sweet leaf bush were investigated. The vegetable was dipped in 0.5% or 1.0% (w/v) of CaCl₂ solutions at 40 °C for 30 s and the control was the untreated sample. Hot CaCl₂ dips significantly delayed the weight loss, maintained the overall quality and inhibited the wiltness (P < 0.05). Both hot CaCl₂ dips had no effect on the changes in lightness (L*) and delayed the decrease in greenness (‐a*) and total chlorophyll content and the increase in both yellowness (b*) and carotenoid content. Hot CaCl₂ dips enhanced total antioxidants, total phenolics content and both AsA‐POD and G‐POD activities from 38.6, 0.44, 15.2 and 22.4 at day 0 to 55.3, 0.55, 50.5 and 362.4 at day 8, respectively. Moreover, hot CaCl₂ dips also delayed the loss of DPPH free radical scavenging activity, total flavonoid, ascorbic acid and CAT activity when compared to other treatments during storage. This study showed that hot CaCl₂ dip maintains postharvest quality and enhanced bioactive compounds of fresh‐cut sweet leaf bush during storage.     

Effect of silane coupling agent treated bovine bone based carbonated hydroxyapatite on in vitro degradation behavior and bioactivity of PLA composites

In this study, effect of treating bovine bone based carbonated hydroxyapatite (CHA) with silane coupling agent on in vitro degradation and bioactivity of PLA composites were investigated. PLA composite specimens containing CHA and silane-treated CHA were immersed in phosphate-buffered solution at 37 °C for the periods of time up to 8 weeks. The changes in specimen weights and morphologies, pH of PBS solution and PLA molecular weight were examined. The results showed that the strong interfacial bonding between silane-treated CHA and PLA matrix significantly delayed in vitro degradation of the PLA composites. However, the bioactivity of the PLA/silane treated CHA composites, determined by the formation of poorly crystalline calcium phosphate compounds on the specimen surface after immersion in simulated body fluid (SBF), seemed to be lower than that of the PLA/CHA composite.     

Effects of mixing technique and filler content on physical properties of bovine bone‐based CHA/PLA composites

This study presented influence of mixing technique as well as filler content on physical and thermal properties of bovine bone‐based carbonated hydroxyapatite (CHA)/poly(lactic acid) (PLA) composites. CHA/PLA composites at various contents of CHA were prepared by either melt‐mixing or solution‐mixing techniques. Thermal properties, morphologies, and mechanical properties of the CHA/PLA composites including molecular weight deterioration of PLA matrices were investigated. Average molecular weights of PLA in the composites prepared by both techniques decreased with increasing CHA content, whereas their molecular weight distributions (MWDs) increased. Nonetheless, average molecular weights of PLA in melt‐mixed composites were lower than those of solution‐mixed composites. With increasing CHA content, elongation at break, tensile strength, and impact strength of the composites were decreased, whereas the tensile moduli of the composites were increased. In comparison between two mixing techniques, the melt‐mixing distributed and dispersed CHA into PLA matrix more effectively than the solution‐mixing did. Therefore, tensile moduli, tensile strength, and impact strength of the melt mixed composites were higher than those of the solution‐mixed composites of the corresponding CHA content. Moreover, decomposition temperatures and % crystallinity of the melt‐mixed composites were higher than those of the solution‐mixed composites. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Application of ultrasonic incorporated with calcium gluconate maintains physicochemical quality of pink guavas during short-term storage at room temperature

Food Science and Biotechnology - The effectiveness of simultaneous calcium gluconate (0.5% w/v) (Ca-G) and ultrasonication (Ca-G + US) on physicochemical quality of pink guavas under...     

4‐Acetamidophenyl acrylate copolymers with acrylonitrile and N‐vinyl‐2‐pyrrolidone: Synthesis,characterization, and reactivity ratios

4‐Acetamidophenyl acrylate (APA) was synthesized and characterized by IR, ¹H and ¹³C NMR spectroscopies. Homo‐ and copolymers of APA with acrylonitrile (AN) and N‐vinyl‐2‐pyrrolidone (NVP) were prepared by a free radical polymerization. All the copolymer compositions have been determined by ¹H NMR technique, and the reactivity ratios of the monomer pairs have been evaluated using the linearization methods Fineman–Ross, Kelen–Tudos, and extended Kelen–Tudos. Nonlinear error‐in‐variable model (EVM) method was used to compare the reactivity ratios. The reactivity ratios for copoly(APA–AN) system were APA(r₁) = 0.70 and AN(r₂) = 0.333, and for copoly(APA–NVP) system the values were APA(r₁) = 4.99 and NVP(r₂) = 0.019. Thermal stability and molecular weights of the copolymers are reported. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1919–1927, 2006     

Ultraviolet-C irradiation maintaining texture and total sugars content of ready to cook baby corn during commercial storage

Food Science and Biotechnology - The aim of this study was to investigate the effects of ultraviolet-C (UV-C) irradiation on the changes in total sugars concentration and texture of ready to cook...     

The Effect of the Electrohydrodynamic on the Two-Phase Flow Pressure Drop of R-134a during Evaporation inside Horizontal Smooth and Micro-Fin Tubes

This article concerns the pressure drop caused by using the electrohydrodynamic (EHD) technique during evaporation of pure R-134a inside smooth and micro-fin tubes. The test section is a counter-flow concentric tube-in-tube heat exchanger where R-134a flows inside the inner tube and hot water flows in the annulus. A smooth tube and micro-fin tube having an inner diameter of 8.12 mm and 8.92 mm, respectively, are used as an inner tube. The length of the inner tube is 2.50 m. The outer tube is a smooth copper tube having an inner diameter of 21.2 mm. The electrode, which is a cylindrical stainless steel wire having diameter of 1.47 mm, is placed in the center of the inner tube. The electrical field is established by connecting a DC high voltage power supply of 2.5 kV to the electrode while the inner tube is grounded. Experiments are conducted at saturation temperatures of 10–20°C, mass fluxes of 200–600 kg/m²s, and heat fluxes of 10–20 kW/m². The experimental results indicate that the application of EHD introduces a small pressure drop penalty. New correlations for the pressure drop are proposed for practical applications.     

An application of machine learning regression to feature selection: a study of logistics performance and economic attribute

Neural Computing and Applications - This study demonstrates how to profit from up-to-date dynamic economic big data, which contributes to selecting economic attributes that indicate logistics...     

Correlations for evaporation heat transfer coefficient and two-phase friction factor for R-134a flowing through horizontal corrugated tubes

Correlations for the evaporation heat transfer coefficient and two-phase friction factor of R-134a flowing through horizontal corrugated tubes are proposed. In the present study, the test section is a horizontal counter-flow concentric tube-in-tube heat exchanger with R-134a flowing in the inner tube and hot water flowing in the annulus. Smooth tube and corrugated tubes with inner diameters of 8.7 mm and lengths of 2000 mm are used as the inner tube. The corrugation pitches are 5.08, 6.35, and 8.46 mm and the corrugation depths are 1, 1.25, and 1.5 mm, respectively. The outer tube is made from smooth copper tube with an inner diameter of 21.2 mm. The correlations presented are formed by using approximately 200 data points for five different corrugated tube geometries and are then proposed in terms of Nusselt number, equivalent Reynolds number, Prandtl number, corrugation pitch and depth, and inside diameter.