Egypt-Japan University of Science and Technology

This paper presents an experimental validation of a decentralized Model Predictive Control (MPC) framework for cooperative object transportation utilizing a multi-robot system consisting of two mobile robots. Each robot is a differential-drive robot that independently solves local constrained optimization problems while ensuring global coordination through joint-space coupling. The formulation explicitly captures nonlinear kinematics, revolute-prismatic joint dynamics, inter-robot constraints, and dynamic obstacle avoidance within a real-time optimization setting. Adaptive weighting of cost terms is employed to balance trajectory tracking and formation objectives under varying task demands. The framework is deployed on a physical testbed integrating vision-based pose estimation, sensor fusion via a Kalman filter, and a ROS2 control infrastructure. Experiments across point-to-point, curvilinear, and obstacle-rich scenarios show accurate trajectory tracking, strict constraint satisfaction, and robustness to environmental uncertainties. These results substantiate decentralized constrained MPC with adaptive weights as a practical and scalable solution for real-time multi-robot cooperative transport along arbitrary reference paths.

New pyrazole/pyrimidine derivatives endowed with azobenzenes were synthesized using microwave and traditional methods. Our compounds were assessed for cytotoxicity against HepG2, MCF-7, HCT-116 and A549 cell lines as dual inhibitors of EGFRT790M and VEGFR-2. A docking study was carried out to show the binding affinities and orientations of our derivatives in the active sites of VEGFR-2 and EGFRT790M. The data of the docking study were highly correlated with the biological data. The HCT116 and A549 cell lines were extremely affected by our derivatives. Derivative 12 showed the greatest activity against A549, HepG2, MCF-7 and HCT116 cells, with IC50 = 5.12, 6.77, 5.85 and 5.25 µM, respectively. It showed higher cytotoxicity than erlotinib (IC50 = 5.49, 7.73, 8.20 and 13.91 µM, respectively) and lower cytotoxicity than sorafenib (IC50 = 4.04, 4.00, 5.58 and 5.05 µM, respectively) against the tested cell lines. The cytotoxicity of the highly active derivatives 5, 6, 8, 9, 10 and 12 against the MCF-10 healthy cell lines was evaluated. The assessed derivatives showed low cytotoxicity against MCF-10 cells, with IC50 = 50.90–55.50 µM. Additionally, all derivatives were assessed as dual VEGFR-2 and EGFRT790M inhibitors. Compounds 12, 8 and 10 displayed very good inhibitions toward VEGFR-2, with IC50 = 0.90, 0.95 and 1.00 µM, respectively. Similarly, structures 12, 8, 10, 5 and 9 showed strong EGFRT790M inhibitions, with IC50 = 0.25, 0.30, 0.33, 0.35 and 0.40 µM, respectively. In addition, in silico ADMET predictions were calculated for the highly active derivatives 8, 10 and 12 and correlated to Lipinski's rule of five using erlotinib and sorafenib as standard ligands. The results presented our derivatives as promising candidates for advanced manipulations to get more potent anticancer agents with advanced VEGFR-2 and EGFRT790M inhibitions.

Both let-7a and miR-34a have been repeatedly studied as pivotal suppressors for Hepatocellular carcinoma; however, their combined regulations remain to be fully elucidated. In the present study, we performed a comprehensive in silico analysis for let-7a and miR-34a using a wealth of updated tools: miRWalk, Genetrail and miRnet. In addition, our study is the first to quantify both miRs and their three predicted yet not experimentally validated oncogenic targets: FNDC3B, IGF2 and SOX4. This was assessed in HepG2 cell model following treatment by PEGP-vector expressing the miRs by MTT assay, florescence microscopy, qPCR and immune-florescence. Our bioinformatics analysis revealed a pool of common predicted hepatocarcinogenic targets shared by both let-7a and miR-34a. Importantly, three targets were identified as co-regulated through multiple canonical binding sites for each miR, and these had not been experimentally validated before. Furthermore, functional enrichment of these putative targets demonstrated their significant involvement in major and emerging HCC hallmarks, such as reprogramming of energy metabolism and evading immune destruction. These findings support our concept of simultaneous co-regulation of these oncogenes through the signaling networks and GO terms associated with both miRs. Consistently, our experimental results verified the significant overexpression of both miRs in HepG2 cells, leading to reduced tumor cell proliferation and decreased levels of the three oncogenic transcripts. Interestingly, miR-34a exhibited a superior suppression effect, reaching 38.7%, and SOX4 was identified as the most significantly downregulated target at both transcriptional and translational levels. Our findings provide new insights into the interconnected anti-HCC effects of let-7a and miR-34a and highlight the potential of applying their combined use to achieve the best therapeutic outcomes for this invasive tumor.