Coronavirus 3C-like protease (3CL Pro ) is a highly conserved cysteine protease employing a catalytic dyad for its functions. 3CL Pro is essential to the viral life cycle and, therefore, is an attractive target for developing antiviral agents. However, the detailed catalytic mechanism of coronavirus 3CL Pro remains largely unknown. We took an integrated approach of employing X-ray crystallography, mutational studies, enzyme kinetics study, and inhibitors to gain insights into the mechanism. Such experimental work is supplemented by computational studies, including the prereaction state analysis, the ab initio calculation of the critical catalytic step, and the molecular dynamic simulation of the wild-type and mutant enzymes. Taken together, such studies allowed us to identify a residue pair (Glu-His) and a conserved His as critical for binding; a conserved GSCGS motif as important for the start of catalysis, a partial negative charge cluster (PNCC) formed by Arg-Tyr-Asp as essential for catalysis, and a conserved water molecule mediating the remote interaction between PNCC and catalytic dyad. The data collected and our insights into the detailed mechanism have allowed us to achieve a good understanding of the difference in catalytic efficiency between 3CL Pro from SARS and MERS, conduct mutational studies to improve the catalytic activity by 8-fold, optimize existing inhibitors to improve the potency by 4-fold, and identify a potential allosteric site for inhibitor design. All such results reinforce each other to support the overall catalytic mechanism proposed herein.

The one-pot seedless protocol provides a facile approach in the synthesis of gold nanostars (AuNS) that involves only three reagents, gold (III) chloride (HAuCl 4 ), silver nitrate (AgNO 3 ) and ascorbic acid (C 6 H 8 O 6 ). While studies correlating the synthesis parameters of the seedmediated protocol to surface-enhance Raman scattering (SERS) enhancement is well reported, the same understanding of the one-pot seedless protocol is limited. Here, we aim to elucidate how the synthesis parameters of AuNS from the one-pot seedless protocol, the AuNS concentration, surface passivation and aggregation level affect the colloidal SERS enhancement. Using crystal violet (CV) as a Raman probe molecule, we found that the SERS enhancement increases with Au 3+ /C 6 H 8 O 6 molar ratio up to 0.60 and Au 3+ /Ag + molar ratio up to 18. Although the surfactant, cetyltrimethylammonium bromide (CTAB) maintained colloidal stability, it reduced the SERS enhancement. Interestingly, the SERS enhancement did not increase monotonically with AuNS concentration, but decreased when AuNS concentration was beyond 15 pM. The SERS enhancement also increased with the increasing level of salt-induced aggregation of AuNS, but only within a few minutes. While the concept of SERS with colloidal nanostructures is not new, we have shown for the first time, a detailed systematic study of various parameters that affect the SERS enhancement of AuNS synthesized using a one-pot seedless protocol. This study enables us to optimize the SERS enhancement of AuNS at the synthesis level to make them effective colloid-based SERS substrates for potential use in intracellular biosensing.

Schematic of study to optimize the SERS enhancement factor of a low cost and facile gold nanostar (AuNS)-based paper-SERS substrate through optimizing the paper materials, immobilization strategies, and SERS acquisition conditions.

A comparable study of the microstructure and magnetic properties was performed for magnetite films deposited on (100)-oriented MgO and SrTiO3 (STO) substrates. The growth of strained high quality Fe3O4 films was confirmed by x-ray diffraction analysis and Raman spectroscopy measurements. The surface morphology and magnetic properties of the two films were found to be obviously different. Moreover, a stripelike magnetic domain structure was observed in the film on STO. Substrate-induced strain is believed to be responsible for these observations, which significantly affects the magnetic anisotropy and the magnetic coupling at the antiphase boundaries in the films.

Employment of identical oxides for the cathode and anode in a symmetrical solid oxide fuel cell (SSOFC) is beneficial for decreasing the fabrication costs of a robust cell. Ce doping on the A-site in SrFeO3 increased the structural stability in a reducing atmosphere, but ceria was found to exsolve from the perovskite during the cooling process in the air if the doping level reached 20 at. %. The additional doping of 5 at. % Ru in Sr0.8Ce0.2FeO3 on the Fe site could prevent the ceria segregation in air and induce the surface decomposition under fuel conditions for the formation of nanoscale SrO, CeO2 and Ru 0 . The SSOFC with Ce/Ru co-doped SrFeO3 on a Sr-and Mg-doped LaGaO3 (LSGM) electrolyte showed a small Rp value (0.12  cm 2 ) when H2 and the ambient air were used as fuel and oxidant, respectively. The peak power densities of 846 mW cm -2 and 310 mW cm -2 were achieved at 800 o C using H2 and C3H8 as fuel, respectively. The excellent coke resistance of the anode could be related to the simultaneous in situ exsolution of CeO2, SrO and Ru 0 nanoparticles.