Selective inhibition of the intrinsic coagulation pathway is a promising strategy for developing safer anticoagulants that do not cause serious bleeding. Intrinsic tenase, the final and rate-limiting enzyme complex in the intrinsic coagulation pathway, is an attractive but less explored target for anticoagulants due to the lack of a pure selective inhibitor. Fucosylated glycosaminoglycan (FG), which has a distinct but complicated and ill-defined structure, is a potent natural anticoagulant with nonselective and adverse activities. Herein we present a range of oligosaccharides prepared via the deacetylationdeaminative cleavage of FG. Analysis of these purified oligosaccharides reveals the precise structure of FG. Among these fragments, nonasaccharide is the minimum fragment that retains the potent selective inhibition of the intrinsic tenase while avoiding the adverse effects of native FG. In vivo, the nonasaccharide shows 97% inhibition of venous thrombus at a dose of 10 mg/kg in rats and has no obvious bleeding risk. This nonasaccharide may therefore serve as a novel promising anticoagulant.T hrombotic disease is seriously harmful to human health and is one of the major causes of death in modern society (1). Despite their long-term and widespread use as anticoagulants, heparin, low-molecular-weight heparin (LMWH), and coumarins still have a major unresolved issue: the risk of serious bleeding during therapy (1-3). It is generally recognized that the risk of bleeding associated with these agents is related to the nonselectivity of their anticoagulant activity. Therefore, selective inhibitors of human factor Xa (FXa) and thrombin (FIIa), such as dabigatran, rivaroxaban, and apixaban, which have predictable pharmacokinetics, have recently been developed; however, these agents have not effectively reduced the risk of bleeding in clinical applications (4-7).Components of the intrinsic coagulation pathway are promising targets for antithrombotic therapy because they are important for thrombosis but are not required for hemostasis (1,8). The development of new anticoagulant agents that inhibit components of the intrinsic pathway and that have a lower risk of causing bleeding has thus become a research focus (9-11). Factor IXa (FIXa), a serine protease, and factor VIIIa (FVIIIa), a protein cofactor, form a Ca 2+ -and phospholipid surface-dependent complex referred to as the intrinsic tenase complex, which efficiently converts zymogen factor X (FX) to FXa (1,12,13). Because the intrinsic tenase is the final and rate-limiting enzyme complex in the intrinsic pathway, the development of inhibitors of this enzyme complex is important for meeting clinical demands (1). However, limited progress has been achieved due to the unavailability of selective inhibitors with welldefined structures.Fucosylated glycosaminoglycan (FG; 1 in Fig. 1), which is a complex acidic polysaccharide isolated from sea cucumber, has recently attracted considerable attention because of its various bioactivities (14). Notably, FG has potent anticoagula...

In lithium-ion secondary batteries research, binders have received the least attention, although the electrochemical performance of Li-ion batteries such as specific capacity and cycle life cannot be achieved if the adhesion strengths between electrode particles and between electrode films and current collectors are insufficient to endure charge-discharge cycling. In this paper, the roles of binders in the mechanical integrity of electrodes for lithium-ion batteries were studied by coupled microscratch and digital image correlation (DIC) techniques. A microscratch based composite model was developed to decouple the carbon particle/particle cohesion strength from the electrode-film/copper-current-collector adhesion strength. The dependences of microscratch coefficient of friction and the critical delamination load on the PVDF binder content suggest that the strength of different interfaces is ranked as follows: Cu/PVDF < carbon-particle/PVDF < PVDF/PVDF. The particle/particle cohesion strength increases while electrode-film/current-collector adhesion strength decreases with increasing PVDF binder content (up to 20% of binder). The electrolyte soaking-and-drying process leads to an increase in particle/particle cohesion but a decrease in electrode-film/copper-current-collector adhesion. Finally, the methodology developed here can provide new guidelines for binder selection and electrode design and lay a constitutive foundation for modeling the mechanical properties and performance of the porous electrodes in lithium-ion batteries.

No abstract