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.     

Amino‐functionalised mesoporous silica microspheres for immobilisation of Candida antarctica lipase B – application towards greener production of 2,5‐furandicarboxylic acid

In the present study, amino‐functionalised mesoporous silica microspheres were utilised as support for the covalent immobilisation of Candida antarctica lipase B (CaLB) for the subsequent production of 2,5‐furandicarboxylic acid (FDCA) from 2,5‐diformylfuran (DFF). Under the optimised operating conditions of pH 6.5, particle/enzyme ratio of 1.25:1.0 and glutaraldehyde concentration of 4 mM, a maximum CaLB immobilisation yield of 82.4% on silica microspheres was obtained in 12.25 h. The immobilised CaLB was used for the synthesis of alkyl esters, which were utilised along with hydrogen peroxide for FDCA synthesis. The biocatalytic conversion of 30 mM DFF dictated a 77–79% FDCA in 48 h at 30°C; where the turnover number and turnover frequency of immobilised CaLB were 6220.73 mol mol⁻¹ and 129.59 h⁻¹, respectively, for ethyl acetate, against 6297.65 mol mol⁻¹ and 131.2 h⁻¹, respectively, for ethyl butyrate. Upon examining the operational stability, the immobilised CaLB exhibited high stability till five cycles of FDCA production.Inspec keywords: mesoporous materials, organic compounds, biotechnology, silicon compounds, renewable materials, catalysis, catalysts, enzymes, thermal stability, biofuelOther keywords: FDCA production, amino‐functionalised mesoporous silica microspheres, greener production, 2,5‐furandicarboxylic acid, covalent immobilisation, 2,5‐diformylfuran, CaLB immobilisation, Candida antarctica lipase B immobilisation, ethyl butyrate, time 48.0 hour, temperature 30.0 degC, time 12.25 hour     

Estimation of magnetohydrodynamic radiative nanofluid flow over a porous non‐linear stretching surface: application in biomedical research

The present study investigates the effects of thermal radiation and chemical reaction on magnetohydrodynamic flow, heat, and mass transfer characteristics of nanofluids such as Cu–water and Ag–water over a non‐linear porous stretching surface in the presence of viscous dissipation and heat generation. Using similarity transformation, the governing boundary layer equations of the problem are transformed into non‐linear ordinary differential equations and solved numerically by the shooting method along with the Runge–Kutta–Fehlberg fourth–fifth‐order integration scheme. The influences of various parameters on velocity, temperature, and concentration profiles of the flow field are analysed and the results are plotted graphically. A backpropagation neural network is applied to predict the skin friction coefficient, Nusselt number, and Sherwood number and these results are presented through graphs. The present numerical results are compared with the existing results and are found to be in good agreement. The results of artificial neural network and the obtained numerical values agree well with an error <5%.Inspec keywords: silver, copper, transforms, nanofluidics, friction, backpropagation, heat radiation, water, external flows, partial differential equations, nonlinear differential equations, boundary layers, Runge‐Kutta methods, mass transfer, flow through porous media, magnetohydrodynamicsOther keywords: magnetohydrodynamic radiative nanofluid flow, nonlinear stretching surface, biomedical research, thermal radiation, chemical reaction, magnetohydrodynamic flow, nonlinear porous stretching surface, viscous dissipation, similarity transformation, governing boundary layer equations, nonlinear ordinary differential equations, shooting method, Runge–Kutta–Fehlberg fourth–fifth‐order integration scheme, flow field, backpropagation neural network, Cu–water nanofluid, Ag–water nanofluid, skin friction coefficient, Nusselt number, Sherwood number, artificial neural network, Ag‐H₂ O, Cu‐H₂ O     

A semantic-aware log generation method for network activities

International Journal of Information Security - Context-aware network logging is becoming more prevalent for enterprise networks, data centers, and forensics. Monitoring agents are strategically...     

Synergic effect of Sn-doped TiO2 nanostructures for enhanced visible light photocatalysis

Journal of Materials Science: Materials in Electronics - In the recent years, metal oxides have attracted more interest for&nbsp;researchers because of their applications in energy and...     

Simultaneous accommodation of Dy3+ at the lattice site of β-Ca3(PO4)2 and t-ZrO2 mixtures: Structural stability,mechanical, optical,and magnetic features

Structurally stable β-Ca₃(PO₄)₂/t-ZrO₂ composite mixtures with the aid of Dy³⁺ stabilizer were accomplished at 1500°C. The precursors comprising Ca²⁺, P⁵⁺, Zr⁴⁺, and Dy³⁺ have been varied to obtain five different combinations. The results revealed the fact that complete phase transformation of calcium-deficient apatite to β-Ca₃(PO₄)₂ occurred only at 1300°C, whereas the evidence of t-ZrO₂ crystallization is obvious at 900°C. The dual occupancy of Dy³⁺ at β-Ca₃(PO₄)₂ and t-ZrO₂ structures was evident; however, Dy³⁺ initially prefers to occupy β-Ca₃(PO₄)₂ lattice until its saturation limit and thereafter accommodates at the lattice site of ZrO₂. The typical absorption and emission behavior of Dy³⁺ were noticed in all the systems and, moreover, the surrounding symmetry of Dy³⁺ domains has been determined from the luminescence study. All the systems ensured paramagnetic response that is generally contributed by the presence of Dy³⁺. A gradual increment in the phase content of t-ZrO₂ in the composite mixtures ensured a significant improvement in the hardness and Young's modulus of the investigated compositions.     

Synthesis and characterization of NiO nanoparticles by sol–gel method

Nickel oxide nanoparticles have been synthesized in the presence of agarose polysaccharide by sol–gel method. The structure, morphology, optical and magnetic properties of the product was examined by X-ray diffraction, transmission electron microscopy, UV–visible spectrophotometer and superconducting quantum interference device magnetometer. The result of thermogravimetric analysis of the precursor product showed that the proper calcination temperature was 400 °C. X-ray diffraction result revealed that the obtained product was nickel oxide with face-centered cubic structure. TEM image demonstrated that the nickel oxide nanoparticles have spherical shape with size around 3 nm. Analysis of FTIR spectra confirmed the composition of product. The optical absorption band gap of the NiO nanoparticles was estimated to be 3.51 eV. Magnetic measurement showed that the nickel oxide nanoparticles exhibit superparamagnetic behavior at 300 K. Moreover, the nanoparticles show ferromagnetic interactions at 4.2 K owing to the existence of uncompensated moments on the surface of the nanoparticles.     

Cache Optimization on Hot‐Point Proxy Caching Using Weighted‐Rank Cache Replacement Policy

The development of proxy caching is essential in the area of video‐on‐demand (VoD) to meet users' expectations. VoD requires high bandwidth and creates high traffic due to the nature of media. Many researchers have developed proxy caching models to reduce bandwidth consumption and traffic. Proxy caching keeps part of a media object to meet the viewing expectations of users without delay and provides interactive playback. If the caching is done continuously, the entire cache space will be exhausted at one stage. Hence, the proxy server must apply cache replacement policies to replace existing objects and allocate the cache space for the incoming objects. Researchers have developed many cache replacement policies by considering several parameters, such as recency, access frequency, cost of retrieval, and size of the object. In this paper, the Weighted‐Rank Cache replacement Policy (WRCP) is proposed. This policy uses such parameters as access frequency, aging, and mean access gap ratio and such functions as size and cost of retrieval. The WRCP applies our previously developed proxy caching model, Hot‐Point Proxy, at four levels of replacement, depending on the cache requirement. Simulation results show that the WRCP outperforms our earlier model, the Dual Cache Replacement Policy.