Like the anti-angiogenic strategy, anti-vascular mimicry is considered as a novel targeting strategy for glioma. In the present study, we used NGR as a targeting ligand and prepared NGR-modified liposomes containing combretastatin A4 (NGR-SSL-CA4) in order to evaluate their potential targeting of glioma tumor cells and vasculogenic mimicry (VM) formed by glioma cells as well as their anti-VM activity in mice with glioma tumor cells. NGR-SSL-CA4 was prepared by a thin-film hydration method. The in vitro targeting of U87-MG (human glioma tumor cells) by NGR-modified liposomes was evaluated. The in vivo targeting activity of NGR-modified liposomes was tested in U87-MG orthotopic tumor-bearing nude mice. The anti-VM activity of NGR-SSL-CA4 was also investigated in vitro and in vivo. The targeting activity of the NGR-modified liposomes was demonstrated by in vitro flow cytometry and in vivo biodistribution. The in vitro anti-VM activity of NGR-SSL-CA4 was indicated in a series of cell migration and VM channel experiments. NGR-SSL-CA4 produced very marked anti-tumor and anti-VM activity in U87-MG orthotopic tumor-bearing mice in vivo. Overall, the NGR-SSL-CA4 has great potential in the multi-targeting therapy of glioma involving U87-MG cells, and the VM formed by U87-MG cells as well as endothelial cells producing anti-U87-MG cells, and anti-VM formed by U87-MG cells as well as anti-endothelial cell activity.

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This study investigates a nocturnal mesoscale convective system (MCS) observed during the Plains Elevated Convection At Night (PECAN) field campaign. A series of wavelike features were observed ahead of this MCS with extensive convective initiation (CI) taking place in the wake of one of these disturbances. Simulations with the WRF-ARW Model were utilized to understand the dynamics of these disturbances and their impact on the MCS. In these simulations, an “elevated bore” formed within an inversion layer aloft in response to the layer being lifted by air flowing up and over the cold pool. As the bore propagated ahead of the MCS, the lifting created an environment more conducive to deep convection allowing the MCS to discretely propagate due to CI in the bore’s wake. The Scorer parameter was somewhat favorable for trapping of this wave energy, although aspects of the environment evolved to be consistent with the expectations for an n = 2 mode deep tropospheric gravity wave. A bore within an inversion layer aloft is reminiscent of disturbances predicted by two-layer hydraulic theory, contrasting with recent studies that suggest bores are frequently initiated by the interaction between the flow within stable nocturnal boundary layer and convectively generated cold pools. Idealized simulations that expand upon this two-layer approach with orography and a well-mixed layer below the inversion suggest that elevated bores provide a possible mechanism for daytime squall lines to remove the capping inversion often found over the Great Plains, particularly in synoptically disturbed environments where vertical shear could create a favorable trapping of wave energy.

Bores have been shown to play a role in the initiation and maintenance of mesoscale convective systems (MCSs), particularly during the night after the boundary layer stabilizes. To date, the generation, evolution, and structure of bores over China has received little attention. This study utilizes observations and simulations with the WRF-ARW model to investigate the generation and evolution of an atmospheric bore observed over Yangtze-Huai Plains of China. The bore was associated with a nocturnal MCS that first formed over elevated terrain. The bore was observed ahead of the MCS with a maximum lateral extension of~100 km. The feature lasted for over 90 mins and propagated at a speed of~13 m/s, slightly faster than the MCS. In the simulation, the bore evolved from the separating "head" of the convectively generated gravity current. The bore then continued to propagate ahead of the MCS, even after the dissipation of the feeder current, and took on the appearance of an undular bore. The bore lifted a layer of convectively unstable air above the nocturnal surface inversion, initiating new convection ahead of the MCS to help maintain the MCS. The Scorer parameter ahead of the bore revealed a low-level wind profile with curvature of the vertical profile of horizontal wind, favoring the trapping of wave energy and the persistence of the bore. These results are generally consistent with the role of bores in the maintenance of nocturnal MCSs and emphasize the need for future studies into the relationship between bores and nocturnal MCSs over China.

In order to investigate the key characteristics of mesoscale convective systems (MCSs) initiated over the Tibetan Plateau (TP) in recent years and the main differences in circulation and environmental factors between different types of MCSs, an automatic MCS identification and tracking method was applied based on the data from China’s Fengyun satellite and precipitation estimates. In total, 8820 MCSs were found to have been initiated over the TP during the summers from 2013 to 2019, and a total of 9.3% of them were able to move eastward out of the TP (EO). The number of MCSs showed a monthly variation, with a maximum in July and a minimum in June, while most EOs occurred in June. Compared with other types of MCSs, EOs usually had a lower cloud-top temperature, a greater rainfall intensity, a longer life duration, more rapid development, larger areas of rainfall and convective clouds, longer tracks and a wider influence range, indicating that EOs are more vigorous than the other types of MCSs. The movement of MCSs is mainly due to the mid- to high-level dynamic conditions, and moisture is an essential factor in their development and maintenance.

Hypoxia is an important microenvironmental pressure present in the majority of solid tumors and, so, tumor hypoxia might be considered an attractive target for tumor therapy. One strategy for targeting hypoxia is to develop bioreductive prodrugs. In the present research, we synthesized a bioreductive paclitaxel prodrug, 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX). The stability of NPPA-PTX in PBS and rat plasma was investigated. The anti-tumor activity of NPPA-PTX was also evaluated in vitro and in vivo. The results of our stability study indicated that NPPA-PTX was stable in PBS and rat plasma as well as in the blood circulation. The in vitro and in vivo anti-tumor activity of NPPA-PTX was confirmed in both KB cells and MDA-MB-231 cells. Our results also indicated that NPPA-PTX could completely convert to active PTX in tumor tissues and produced the anti-tumor activity in both KB and MDA-MB-231 tumor-bearing nude mice. We suggest that the dissociated PTX which converted from NPPA-PTX in tumor tissues played a key role in producing anti-tumor activity. Considering all our results, we suggest that NPPA-PTX is a novel bioreductive PTX prodrug which could undergo further evaluation.