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Sulfonium‐ion‐containing polymers exhibit significant potential benefits for various applications. An efficient strategy to synthesize a type of antibacterial sulfonium‐ion‐bearing polypeptoids via a combination of ring‐opening polymerization and a post‐polymerization functionalization with various functional epoxides is presented. A systematic investigation is further performed in order to explore the influence of the overall hydrophobic/hydrophilic balance on the antimicrobial activity and selectivity of the prepared polysulfoniums. Notably, those chlorepoxypropane‐modified polysulfoniums with an optimized amphiphilic balance show higher selectivity toward both Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus, than to red blood cells. The polymers also show great efficiency in inhibiting S. aureus biofilm formations, as well as in further eradicating the mature biofilms. Remarkably, negligible antibacterial resistance and cross‐resistance to commercial antibiotics is shown in these polymers. The polysulfoniums further show their potent in vivo antimicrobial efficacy in a multidrug‐resistant S. aureus infection model that is developed on mouse skin. Similar to the antimicrobial peptides, the polysulfoniums are demonstrated to kill bacteria through membrane disruption. The obtained polypeptoid sulfoniums, with high selectivity and potent antibacterial property, are excellent candidates for antibacterial treatment and open up new possibilities for the preparation of a class of innovative antimicrobials.

Summary. Inhibitors of the platelet glycoprotein (GP)IIb-IIIa receptor (integrin a IIb b 3 ) reduce acute thrombotic events in patients with coronary artery disease. To characterize the mechanism of action of these drugs, we evaluated the effects of different GPIIb-IIIa antagonists on shear-induced platelet aggregation, activation, and the expression of procoagulant activity. Samples of platelet-rich plasma from 16 volunteers were exposed to the shear rate of 10 800 s À1 for 6 min in an optically modi®ed cone-plate viscometer. Abciximab, tiro®ban and epti®batide inhibited aggregation to a similar extent (mean AE SD: 74.1 AE 8.5%, 69.5 AE 13.6%, 65.6 AE 17.0%, respectively), but only abciximab inhibited signi®cantly microparticle release associated with shear-induced platelet activation (64.4 AE 13.6%, P 2.2 Â 10 À7 ; tiro®ban 20.0 AE 23.4%; epti®batide 23.9 AE 17.4%). P-selectin platelet surface translocation was also strongly inhibited by abciximab, weakly by epti®batide, but not by tiro®ban. The addition of anti-a v b 3 to tiro®ban enhanced the inhibiting effects on shear-induced P-selectin translocation and microparticle release. Shearing of plateletrich plasma shortened the re-calci®cation clotting time after addition of kaolin from 106.9 AE 14.3 to 94.2 AE 10.7 s (mean AE SD; P 0.0013). This effect, which is mediated by the appearance of procoagulant phospholipids on the surface of sheared platelets and microparticles, was prevented by abciximab and by the combination of tiro®ban and anti-a v b 3 , but not by tiro®ban alone or epti®batide. The ability to inhibit shearinduced platelet activation, as evidenced by microparticle release and P-selectin surface translocation as well as the expression of procoagulant activity, differentiates the effects of antiGPIIb-IIIa agents, which may explain the distinct antithrombotic ef®cacy of the agents.

This is the first study to demonstrate that ginsenoside Rb1 preconditioning has protective effects on myocardial ischemia and reperfusion injury, partly by mediating the activation of the PI3K pathway and phosphorylation of Akt.

Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (Aβ) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models. We found that NRBF2 interacts with APP in vivo and its expression levels are reduced in hippocampus of 5XFAD AD mice; we further demonstrated that NRBF2 overexpression promotes degradation of APP C-terminal fragments (APP-CTFs), and reduces Aβ and Aβ levels in human mutant APP-overexpressing cells. Conversely, APP-CTFs, Aβ and Aβ levels were increased in Nrbf2 knockdown or nrbf2 knockout cells. Furthermore, NRBF2 positively regulates autophagy in neuronal cells and NRBF2-mediated reduction of APP-CTFs levels is autophagy dependent. Importantly, nrbf2 knockout attenuates the recruitment of APP and APP-CTFs into phagophores and the sorting of APP and APP-CTFs into endosomal intralumenal vesicles, which is accompanied by the accumulation of the APP and APP-CTFs into RAB5-positive early endosomes. Collectively, our results reveal the potential connection between NRBF2 and the AD-associated protein APP by showing that NRBF2 plays an important role in regulating degradation of APP-CTFs through modulating autophagy.