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In this paper, we establish the global existence and uniqueness of regular solutions to the Cauchy problem for the reduced gravity two-and-a-half layer model with large data in 1-D. In view of the singular structure of this model, we introduce some new variables, combining with the Bresch-Desjardins entropy estimates and the transport properties of $ X_i = u_i+\frac{\partial_xh_i}{h_i} $ to obtain the required uniform a priori estimates. Moreover, the regular solution $ (h_i,u_i) $ satisfies that $ h_i>0 $ for all point $ x\in\mathbb{R} $ but decays to zero in the far field, and we also give the proof for the non-existence of global regular solutions with $ L^\infty(\mathbb{R}) $ decay on $ u_i $. These results are inspired by Cao, Li and Zhu [SIAM J. Math. Anal., 54(2022), pp. 4658-4694], and generalize previous results on global strong solutions with positive lower bounds on the initial data $ h_i^0 $. [ABSTRACT FROM AUTHOR]

Rationale: 212 Pb, a promising in vivo alpha - particle generator of 212 Bi, has aroused much interest as a therapeutic radionuclide. For the development of targeted alpha therapy (TAT), it is important to determine the contribution of targeted effects in irradiated cells, and also of non-targeted effects in non-irradiated bystander cells. Currently, the critical roles of mitochondrial transfer in cellular crosstalk have garnered significant attention. However, the specific involvement of damaged mitochondrial transfer in orchestrating this alpha-particle radiation-induced bystander effect (RIBE) needs to be further explored. Methods: A novel alpha-emitting radiopharmaceutical, 212 Pb-hydrogel nanoparticles (HNPs), was synthesized and subsequently evaluated its theranostics effects. The impact of irradiated cell-conditioned media (ICCM), collected at different times post- 212 Bi irradiation, on bystander cancer cells regarding cell viability was also investigated. Additionally, damaged mitochondria were isolated and cultured with non-irradiated bystander cells to assess their role. Results: 212 Pb-HNPs exhibited efficient therapeutic antitumor effects in vitro , including increased GSH depletion, ROS accumulation, and mitochondrial damage in irradiated tumor cells. In vivo studies demonstrated its imaging potential through SPECT/CT, and RNA sequencing results indicated activation of oxidative stress-related pathways in irradiated tumors. Additionally, ICCM influenced the viability of non-irradiated bystander cells, suggesting a radiation-induced bystander effect by the alpha-particle 212 Bi. Interestingly, damaged mitochondria isolated from ICCM were observed to enter co-cultured non-irradiated bystander cells. Further experiments confirmed that the transfer of damaged mitochondria results in the death of non-irradiated bystander cells. Conclusion: The present study highlights the theranostic potential of the alpha-particle generator 212 Pb and, more importantly, elucidates the role of damaged mitochondrial transfer in alpha-particle RIBE. These findings provide a novel theoretical mechanism for the antitumor effects of alpha-particles and expand the clinical application prospects of TAT., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Cinnamomi cortex (CC), a traditional Chinese herbal medicine, exhibits antidiabetic properties, yet the underlying mechanisms are not fully understood. Our study combined network pharmacology, molecular docking, and experimental validation to elucidate the antidiabetic mechanisms of CC., Methods: Active components of CC and their potential antidiabetic targets were identified through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database. Molecular docking with core targets was performed using Autodock Vina. The efficacy of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the T2DM mouse., Results: Eleven active components and sixty-six potential antidiabetic targets of CC were identified. The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects., Conclusion: CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated inflammation, providing a multi-pathway therapeutic approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)