Blood-Brain Barrier-Penetrating and Lesion-Targeting Nanoplatforms Inspired by the Pathophysiological Features for Synergistic Ischemic Stroke Therapy.

Ischemic stroke is a dreadful vascular disorder that poses enormous threats to the public health. Due to its complicated pathophysiological features, current treatment options after ischemic stroke attack remains unsatisfactory. Insufficient drug delivery to ischemic lesions impeded by the blood-brain barrier (BBB) largely limits the therapeutic efficacy of most anti-stroke agents. Herein, inspired by the rapid BBB penetrability of 4T1 tumor cells upon their brain metastasis and natural roles of platelet in targeting injured vasculatures, a bio-derived nanojacket is developed by fusing 4T1 tumor cell membrane with platelet membrane, which further clothes on the surface of paeonol and polymetformin-loaded liposome to obtain biomimetic nanoplatforms (PP@PCL) for ischemic stroke treatment. The designed PP@PCL could remarkably alleviate ischemia-reperfusion injury by efficiently targeting ischemic lesion, preventing neuroinflammation, scavenging excess reactive oxygen species (ROS), reprogramming microglia phenotypes, and promoting angiogenesis due to the synergistic therapeutic mechanisms that anchor the pathophysiological characteristics of ischemic stroke. As a result, PP@PCL exerts desirable therapeutic efficacy in injured PC12 neuronal cells and rat model of ischemic stroke, which significantly attenuates neuronal apoptosis, reduces infarct volume, and recovers neurological functions, bringing new insights into exploiting promising treatment strategies for cerebral ischemic stroke management.

Post-pollination barriers contribute to coexistence of partially pollinator-sharing Arisaema species (Araceae).

Reproductive isolation plays an important role in maintaining the species integrity of sympatric close relatives. For sympatric Arisaema species, interspecific gene flow is expected to be effectively prevented by pre-pollination barriers, particularly strong pollinator isolation mediated by fungus gnats. However, due to the lack of quantitative studies combining multiple pre- and post-pollination barriers, it is not known whether pre-pollination isolation is complete, and whether post-pollination barriers also contribute to reproductive isolation among some Arisaema species. In this study, we quantified the individual strengths and absolute contributions of four pre- and post-pollination barriers (phenological isolation, pollinator isolation, hybrid fruit formation, and hybrid seed formation) among three sympatric Arisaema species (A. bockii, A. lobatum, and A. erubescens). Although phenological isolation and pollinator isolation reduced the frequencies of interspecific pollen transfer among these species, the partial overlap of flowering times and pollinator assemblages resulted in incomplete pre-pollination isolation. Post-pollination barriers also contributed to reproductive isolation at the hybrid fruit and seed formation stages. We propose that, although pre-pollination barriers are expected to contribute more to total isolation than post-pollination barriers in Arisaema, pre-pollination barriers may not completely prevent interspecific pollen transfer among some Arisaema species. Post-pollination barriers, which are generally ignored, may also have contributed significantly to reproductive isolation in Arisaema.