Synthesis and biological evaluation of arylpiperazine derivatives as potential anti-prostate cancer agents.

A novel scaffold of arylpiperazine derivatives was discovered as potent androgen receptor (AR) antagonist through rational drug designation based on our pre-work, leading to the discovery of a series of new antiproliferative compounds. Compounds 10, 16, 27, 29 and 31 exhibited relatively strong antagonistic potency against AR and exhibited potent AR binding affinities, while compounds 5, 6, 10, 14, 16, 19, 21, 27 and 31 exhibited strong cytotoxic activities against LNCaP cells (AR-rich) as well as also displayed the higher activities than finasteride toward PC-3 (AR-deficient) and DU145 (AR-deficient). Docking study suggested that the most potent antagonist 16 mainly bind to AR ligand binding pocket (LBP) site through hydrogen bonding interactions. The structure-activity relationship (SAR) of these designed arylpiperazine derivatives was rationally explored and discussed. These results indicated that the novel scaffold compounds demonstrated a step towards the development of novel and improved AR antagonists, and promising candidates for future development were identified.

Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives.

For the development of potential anti-prostate cancer agents, 24 kinds of novel naftopidil-based arylpiperazine derivatives have been synthesized and characterized by spectroscopic methods. Their antitumor activities were evaluated against several classical prostate cancer cell lines including PC-3, LNCaP, and DU145. Among all the compounds, 9, 13, 17, 21 and 27 showed strong cytotoxic activities against DU145 cells (IC50 < 1 µM). Further testing confirmed that compound 17 inhibited the growth of DU145 cells by inducing cell cycle arrest at G0/G1 phase. Besides, antagonistic activities of compounds (9, 13, 17, 21 and 27) towards a1-ARs (α1A, α1B, and α1D) were further evaluated using dual-luciferase reporter assays, and the compounds 13 and 17 exhibited better a1-ARs subtype selectivity. The structure-activity relationship (SAR) of these developed arylpiperazine derivatives was rationally discussed. Taken together, these results suggested that further development of such compounds may be of great interest.

Cancer risk assessment in modern radiotherapy workflow with medical big data.

Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose-response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI.

Diaquabis(quinoxaline-2-carboxylato-kappa2N1,O)copper(II).

In the title compound, [Cu(C9H5N2O2)2(H2O)2], the Cu(II) ion lies on an inversion centre and has an elongated centrosymmetric octahedral environment, equatorially trans-coordinated by two N,O-bidentate quinoxaline-2-carboxylate ligands and axially coordinated by two water O atoms. Symmetry-related molecules are linked by strong O-H...O hydrogen bonds, involving the uncoordinated carboxyl O atom of the carboxylate group and the coordinated water molecules, to form a two-dimensional network. Weak intermolecular C-H...N interactions also stabilize the crystal structure.

[Influence of projection data correction on digital breast tomosynthesis imaging].

OBJECTIVE: To investigate the effect of detector performance during digital breast tomography (DBT) projection data acquisition on reconstructed image quality. METHODS: With reference to the traditional detector data correction method and the specific data acquisition pattern in DBT imaging, we utilized dark field correction, light field and its gain correction for processing the projection data collected by the detector. The reconstructed images were evaluated using iterative reconstruction method based on total generalized variation (TGV). RESULTS: In physical breast phantom experiment, the proposed method resulted in a reduced Heel effect caused by nonuniform photon number. The reconstructed DBT images after correction showed obviously improved image quality especially in the details with a low contrast. CONCLUSION: The dark field correction, light field and its gain correction process for DBT image reconstruction can improve the image quality.

[Sinogram restoration for low-dose cerebral perfusion CT images].

OBJECTIVE: In clinical cerebral perfusion CT examination, repeated scanning the region of interest in the cine mode increases the radiation dose of the patients, while decreasing the radiation dose by lowering the scanning current results in poor image quality and affects the clinical diagnosis. We propose a penalized weighted least-square (PWLS) method for recovering the projection data to improve the quality of low-dose cerebral perfusion CT imaged. This method incorporates the statistical distribution characteristics of brain perfusion CT projection data and uses the statistical properties of the projection data for modeling. The PWLS method was used to recover the data, and the Gauss-Seidel (GS) method was employed for iterative solving. Adaptive weighting is introduced between the original projection data and the projection data after PWLS restoration. The experimental results on the clinical data demonstrated that the PWLS-based sinogram restoration method improved noise reduction and artifact suppression as compared with the conventional noise reduction methods, and better retained the edges and details to generate better cerebral perfusion maps.

[Mechanism of Cr( VI) removal from aqueous solution using biochar promoted by humic acid].

Biochar derived from excess sludge was used for hexavalent chromium [Cr( VI)] removal from water as a sorbent, and impacts of co-existing humic acid on performance of Cr( VI) sorption onto biochar were studied. The experimental results indicated that humic acid facilitated biochar adsorption of Cr(VI), which enhanced capacity of Cr sorption and shortened reaction time reaching equilibrium remarkably. The sorption kinetic process could be described with the pseudo second order model. On the condition of initial pH 4.0, biochar concentration 20 g x L(-1), initial concentration of Cr(VI) in the range of 50-800 mg x L(-1), the Langmuir model fitted adsorption isotherm better than the Freudlich model. The Langmuir Q0 values of biochar with and without existing humic acid were 10.10 mg x g(-1) and 5.56 mg x g(-1), respectively. In the pH range of 2.0-8.0, sorption capacity of all sorbents decreased with increasing initial pH value. Ascending concentration of humic acid in solution promoted sorption capacity of biochar. Fourier transform infrared spectroscopy (FTIR) analysis showed that hydroxyl, carboxyl, ester, aromatic C-H stretch and ring C=C on the biochar were responsible for Cr(VI) sorption. Combined with X-ray photoelectron spectroscopy (XPS) analysis, mechanism of promoting Cr( VI) sorption onto biochar was speculated that humic acid enhanced concentration of Cr( VI) ions aggregating on the surface of biochar and benefited Cr(VI) adsorption coupled with subsequent reduction by biochar functional groups. Meanwhile, humic acid also increased amount of Cr(VI) and Cr(II) removal from aqueous solution.