Multiple and complex mechanisms involving mobile genetic elements in class 1 and class 2 integrons and antibiotic resistance have been developed in the evolution of Shigella strains.

Increased hemichannel opening induced by oxygen glucose deprivation (OGD) was reported in the hippocampal pyramidal neuron. It was suggested that the pannexin1 hemichannel opening could mediate ionic flux dysregulation, anoxic depolarization, and energy-depleting efflux of glucose and ATP for ischemic neurons. However, the regulatory mechanisms of pannexin1 hemichannel opening have been poorly understood. Here we showed that excessive generation of nitric oxide (NO) during ischemia could induce the calcein leakage from neurons, which was markedly reduced by NO synthase inhibitor. The calcein leakage from neurons during OGD was also attenuated by the application of N-ethylmaleimide (NEM), an SH-alkylating agent, and dithiothreitol (DTT), a reducer of oxidized sulfhydryl groups. However, the soluble guanylyl cyclase (sGC) inhibitor had a minor effect on the calcein leakage during OGD. Furthermore, the elevated intracellular but not extracellular levels of glutathione could also inhibit the calcein leakage during OGD. Similar results were observed in metabolic inhibition (MI), which is another ischemic-like condition. Finally, immunocytochemical and immunoblotting analysis revealed that, after 1 hr of OGD stimulation, the distribution and expression of pannexin1 showed no significant difference compared with control. However, the pannexin1 mRNA expression was elevated after 1 hr of OGD and a sustained increase was maintained during reperfusion. These results implied that the reactive oxygen species (ROS), especially NO, might be involved in the enhanced pannexin1 hemichannel opening and that the S-nitrosylation but not the NO/cGMP pathway played a more important role in this event.

A thorough understanding of the spatiotemporal dynamics of blood supply and tissue viability is of great importance in stroke researches. In the current study, vascular and cellular responses to focal ischemia were monitored with optical coherence tomography on chronic rat photothrombotic stroke model. The 3D mapping of blood perfusion and cellular scattering were achieved by analyzing the temporal dynamics and depth attenuation of intrinsic backscattered light respectively. Optical coherence tomography revealed that vessels of different types presented various spatial and temporal dynamics during the photothrombotic occlusion and the later recovery period. The large distal middle cerebral arteries presented a spontaneous recanalization and the small pial microvessels presented a reperfusion along with newly appeared vessels from the peripheral into the core area. The cortical capillary perfusion presented a weak recovery. Compared to the male group, the female rats showed a faster vascular recovery after photothrombotic. Moreover, the dynamic changes of the cellular scattering signal showed a high spatial and temporal correlation with the cortical capillary perfusion. Combined with well-designed photothrombotic stroke model and chronic optical window, optical coherence tomography imaging offers a unique approach to improve the understanding of stroke procedure and evaluate the treatment outcomes.

Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (−21.63±0.91 mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN 3 /deoxyglucose or low temperature). The endocytosis inhibitors (methyl-β-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine) dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2α-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2α and elevated level of activating transcription factor 4). CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase-4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal) significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our findings provide important new insights into QDs toxicity and reveal potential cardiovascular risks for the future applications of QDs.