Virtually all biomaterials are susceptible to biofilm formation and, as a consequence, device-associated infection. The concept of an immobilized liquid surface, termed slippery liquid-infused porous surfaces (SLIPS), represents a new framework for creating a stable, dynamic, omniphobic surface that displays ultralow adhesion and limits bacterial biofilm formation. A widely used biomaterial in clinical care, expanded polytetrafluoroethylene (ePTFE), infused with various perfluorocarbon liquids generated SLIPS surfaces that exhibited a 99% reduction in S. aureus adhesion with preservation of macrophage viability, phagocytosis, and bactericidal function. Notably, SLIPS modification of ePTFE prevents device infection after S. aureus challenge in vivo, while eliciting a significantly attenuated innate immune response. SLIPS-modified implants also decrease macrophage inflammatory cytokine expression in vitro, which likely contributed to the presence of a thinner fibrous capsule in the absence of bacterial challenge. SLIPS is an easily implementable technology that provides a promising approach to substantially reduce the risk of device infection and associated patient morbidity, as well as health care costs.

The main protease (M pro ) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV M pro exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV M pro dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV M pro C-terminal domain alone (residues 187 to 306; M pro -C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The M pro -C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV M pro also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the M pro -C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV M pro . Our study results help to clarify previously published controversial claims about the role of the N-finger in SARSCoV M pro dimerization. Apparently, without the N-finger, SARS-CoV M pro can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV M pro is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.

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ABSTRACT

SARS coronavirus main protease (M pro ) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. We have reported that both the M pro C-terminal domain alone (M pro -C) and the N-finger deletion mutant of M pro (M pro -D7) exist as a stable dimer and a stable monomer (Zhong et al., J Virol 2008; 82:4227-4234). Here, we report structures of both M pro -C monomer and dimer. The structure of the M pro -C monomer is almost identical to that of the C-terminal domain in the crystal structure of M pro . Interestingly, the M pro -C dimer structure is characterized by 3D domain-swapping, in which the first helices of the two protomers are interchanged and each is enwrapped by four other helices from the other protomer. Each folding subunit of the M pro -C domain-swapped dimer still has the same general fold as that of the M pro -C monomer. This special dimerization elucidates the structural basis for the observation that there is no exchange between monomeric and dimeric forms of M pro -C and M pro -D7.

Monomer design plays an important role in the development of polymers with desired thermal properties and chemical recyclability. Here we prepared a class of sevenmembered ring carbonates containing trans-cyclohexyl fused rings. These monomers showed excellent activity for ring-opening polymerization (ROP) with turnover frequency (TOF) up to 6 × 10 5 h −1 and catalyst loading down to 50 ppm, which yielded highmolecular-weight polycarbonates (M n up to 673 kg/mol) with great thermostability (T d > 300 °C). Ultimately, the resulting polycarbonates can completely depolymerize into their corresponding cyclic dimers that can repolymerize to synthesize the starting polymers in moderate yields, demonstrating a potential route to achieve chemical recycling. Postfunctionalization of the unsaturated polycarbonate was conducted through cross-linking reaction and "click" reaction under UV irradiation.

Objective Syndecan-1 (Sdc-1) is a member of a family of cell surface proteoglycans that has been reported to participate in the regulation of events relevant to tissue repair and chronic injury responses, including cell-substrate interactions, matrix remodeling and cell migration. In this study, we report the functional significance of Sdc-1 in polarized macrophage populations and their role in adhesion and motility events relevant to resolution of the inflammatory program. Approach and Results Macrophage Sdc-1 expression is associated with differentiated M2 macrophages with high intrinsic motility and Sdc-1 deficiency is characterized by impaired migration and enhanced adhesion. Leukocyte infiltration and emigration were examined in a thioglycollate-induced model of peritonitis in Sdc-1+/+ and Sdc-1−/− mice. Although the infiltration of inflammatory cells was similar in both cohorts, a significant delay in the lymphatic clearance of Sdc-1−/− macrophages was observed. Moreover, we observed enhanced inflammation and greater burden of atherosclerotic plaque in ApoE−/−Sdc-1−/− mice maintained on a Western diet. Conclusions These results demonstrate that defective motility in Sdc-1−/− macrophages promotes a persistent inflammatory state with relevance to the pathogenesis of atherosclerosis.