Preparation and Properties of Egg White Dual Cross-Linked Hydrogel with Potential Application for Bone Tissue Engineering.

In this study, an egg white dual cross-linked hydrogel was developed based on the principle that the external stimulus can denature proteins and cause them to aggregate, forming hydrogel. The sodium hydroxide was used to induce gelation of the egg white protein, subsequently introducing calcium ions to cross-link with protein chains, thereby producing a dual cross-linked hydrogel. The characteristics of the dual cross-linked hydrogels-including the secondary structure, stability, microstructure, swelling performance, texture properties, and biosafety-were investigated to determine the effects of calcium ion on the egg white hydrogel (EWG) and evaluate the potential application in the field of tissue engineering. Results showed that calcium ions could change the ß-sheet content of the protein in EWG after soaking it in different concentrations of CaCl2 solution, leading to changes in the hydrogen bonds and the secondary structure of polypeptide chains. It was confirmed that calcium ions promoted the secondary cross-linking of the protein chain, which facilitated polypeptide folding and aggregation, resulting in enhanced stability of the egg white dual cross-linked hydrogel. Furthermore, the swelling capacity of the EWG decreased with increasing concentration of calcium ions, and the texture properties including hardness, cohesiveness and springiness of the hydrogels were improved. In addition, the calcium cross-linked EWG hydrogels exhibited biocompatibility and cell-surface adhesion in vitro. Hence, this work develops a versatile strategy to fabricate dual cross-linked protein hydrogel with biosafety and cell-surface adhesion, and both the strategy and calcium-egg white cross-linked hydrogels have potential for use in bone tissue engineering.

Multiscale U-Net with Spatial Positional Attention for Retinal Vessel Segmentation.

Retinal vessel segmentation is essential for the detection and diagnosis of eye diseases. However, it is difficult to accurately identify the vessel boundary due to the large variations of scale in the retinal vessels and the low contrast between the vessel and the background. Deep learning has a good effect on retinal vessel segmentation since it can capture representative and distinguishing features for retinal vessels. An improved U-Net algorithm for retinal vessel segmentation is proposed in this paper. To better identify vessel boundaries, the traditional convolutional operation CNN is replaced by a global convolutional network and boundary refinement in the coding part. To better divide the blood vessel and background, the improved position attention module and channel attention module are introduced in the jumping connection part. Multiscale input and multiscale dense feature pyramid cascade modules are used to better obtain feature information. In the decoding part, convolutional long and short memory networks and deep dilated convolution are used to extract features. In public datasets, DRIVE and CHASE_DB1, the accuracy reached 96.99% and 97.51%. The average performance of the proposed algorithm is better than that of existing algorithms.

Synthesis, cytotoxic activity, and 2D- and 3D-QSAR studies of 19-carboxyl-modified novel isosteviol derivatives as potential anticancer agents.

Two series of novel acylthiosemicarbazide and oxadiazole fused-isosteviol derivatives were synthesized based on the 19-carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines (HCT-116, HGC-27, and JEKO-1) using an MTT assay. Lead compounds from the acylthiosemicarbazides (4) showed IC50 values in the lower micromolar range. For example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory activities against the three cell lines with IC50 values of 0.95-3.36 µm. Furthermore, 2D-HQSAR and 3D-topomer CoMFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.

Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents.

A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50 value of 2.987±0.098µM, which was better than that (3.906±0.261µM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r2=0.848, q2=0.544 and R2pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.

Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents.

A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 µM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule.

Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents.

Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 µM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 µM, respectively).

Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents.

Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 µM) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.

Stereoselective synthesis of bioactive isosteviol derivatives as alpha-glucosidase inhibitors.

Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors.