Synthesis of C3'-Foused Aryl/Penta-1,4-Dien-3-One/Amine Hybrids as HSP90C-Terminal Inhibitors.

24 C3'-focused hybrids of aryl/penta-1,4-dien-3-one/amine (APDA) were designed and synthesized. Of these hybrids, 2 n demonstrated improved antiproliferative effects on HER2-positive breast cancer cells (SKBr3 and BT474) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) with IC50 values ranging from 7.45 to 10.75 µM, but less toxicity to normal breast cells MCF-10A than the first generation of hybrid 1. Additionally, 2 n retained its ability to inhibit HSP90C-terminus, leading to the degradation of HSP90 client proteins HER2, EGFR, pAKT, AKT, and CDK4, without inducing a heat-shock response. Notably, 2 n also demonstrated improved thermostability compared to 1 and maintained in vitro metabolic stability in simulated intestinal fluid. These findings will provide a scientific basis for developing HSP90C-terminal inhibitors in the future.

miR-517b-3p promotes the progression of portal vein tumor thrombus via activating Wnt/ß-catenin signaling pathway in hepatocellular carcinoma.

AIMS: This study was aimed to investigate the expression patterns and prognostic value of microRNA-517b-3p (miR-517b-3p) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS: The expression of miR-517b-3p in PVTT tissues and cells was estimated using qRT-PCR. Through Kaplan-Meier survival analysis, Cox regression assay and ROC analysis, the significance of miR-517b-3p was explored. In addition, cell experiments were performed to examine the functional role of miR-517b-3p during progression of PVTT. Moreover, the biological process and biological pathway analysis analyses were conducted through GSEA and FunRich. Besides, the protein-protein interaction (PPI) network of the DEGs was established through cBioPortal website. RESULTS: Compared with the controls, the miR-517b-3p was upregulated in both PVTT tissues and cells. The upregulated miR-517b-3p, which served as a potential diagnostic biomarker to distinguish PVTT from PT and controls, was associated with poor overall survival and acted as an independent prognostic factor. The cell proliferation, migration and invasion were proved to be enhanced by overexpression of miR-517b-3p. Furthermore, Wnt/ß-catenin signaling was suppressed by miR-517b-3p knockdown and might be involved in the progression of PVTT. CONCLUSION: miR-517b-3p may promote PVTT cell proliferation, migration and invasion via activation of Wnt/ß-catenin signaling pathway. Meanwhile, miR-517b-3p has overexpression in PVTT samples, and serves as a candidate diagnostic and prognostic biomarker in HCC patients with PVTT.

[A river stretch scale assessment of urban river habitat in the Taihu Lake Basin]. / 基于河段尺度的太湖流域城市河流生境评价.

Under the background of rapid urbanization, the degradation of urban river water environment and ecological function in the Taihu Lake Basin has become increasingly prominent. Consequently, it is particularly important to systematically assess urban river habitat. This study referred to and corrected the British Urban River Survey evaluation system. Based on the characte-ristics of urban rivers in the Taihu Lake Basin, we established the evaluation system of stretch habitat quality index (SHQI) of urban river stretches and analyzed the urban river habitat status and spatial variation in the Taihu Lake Basin. The results showed that the SHQI values of the 50 river stretches ranged between 8 and 21, with 3 river stretches classified as "excellent" habitat level, 6 as "good", 27 as "moderate", 9 as "poor", and 5 as "very poor". The vegetation index in urban river habitats in the Taihu Lake Basin was good, whereas that of the physical habitat and material index were bad. The overall ranking of habitats was Zhenjiang: Huzhou: Hangzhou: Jiaxing: Suzhou: Wuxi: Changzhou. There were significant differences in physical habitats, material indices and pollution indices among different cities. The main stream and the tributary section significantly differed in the material index and pollution index, but not significant for SHQI. The evaluation system constructed in this study reflected the current situation of urban river habitats in the Taihu Lake Basin, and could provide guidance for ecological restoration of urban rivers.

[A multi-phase flow detector system based on gamma-ray].

In the present paper, a gamma-ray based on-line detection system was designed for multi-phase flow measurement, where the complicated fluid property of multi-phase flow can be studied by using the principle of ray transmission. The system is made up of three parts, i. e., the sensing unit, the signal conditioning & processing unit and the computer imaging unit. The sensing unit consists of five 241 Am sources with principal energy of 59.5 keV and five sets of CdZnTe semiconductor detectors by using the Geant 4 simulating software toolkits. The sources and detectors are mounted equally at the cross section of pipeline to detect different phase medium simultaneously. This function of the system guarantees the real-time performance of the on-line detecting. In order to improve the accuracy of the probe, a low noise probe circuit was designed, including a low noise charge-sensitive preamplifier, a low noise amplifier, filter circuit and an eliminated zero-poles circuit. Some of the emitted gamma-ray photons from the radiation sources are detected by the sensing element, where the photo energy is transferred into electrical energy by using CdZnTe semiconductor detectors. The output of the sensing element is sent to the signal conditioning & processing unit, which is amplified and filtered to be a level-discriminated signal. Finally, the output of the signal conditioning & processing unit is sent to the computer imaging unit, in which the 2D images are reconstructed by using a certain reconstruction algorithm. Under the normal temperature, the system performs the test of energy spectrum and then it has better energy resolution about 4.38% for 241 Am 59.5 keV. The result reveals that our system has higher probe accuracy. Using experimental data, the images are reconstructed with Filter back projection (FBP) reconstruction algorithm. Images of high quality are achieved.