Binding of synthetic nanobodies to the SARS-CoV-2 receptor-binding domain: the importance of salt bridges.

In this study, five different SARS-CoV-2 receptor-binding domain (RBD) models were created based on the crystal structures of RBD complexes with two synthetic nanobodies (Sb16 and Sb45). Microsecond all-atom MD simulations revealed that Sb16 and Sb45 substantially stabilized the flexible RBD loop (residues GLU471-SER494) due to the salt bridges and hydrogen bonding interactions between RBD and the synthetic nanobodies. However, the calculation of binding free energy displayed that Sb45 had a higher binding affinity to RBD than Sb16, in agreement with the experimental result. This is because Sb45 has stronger electrostatic attraction to RBD as compared to Sb16. In particular, the salt bridge GLU484-ARG33 in Sb45-RBD is stronger than the GLU484-LYS32 in Sb16-RBD. Furthermore, by comparing the binding affinity of Sb16 for two RBD mutants (E484K and K417N), we found that E484K mutation substantially reduced the binding affinity to Sb16, and K417N mutation had no significant effect, qualitatively in agreement with experimental studies. According to the binding free energy calculation, the strong electrostatic repulsion between LYS32 and LYS484 caused by E484K mutation destroys the salt bridge between LYS32 and GLU484 in the RBD wild type (WT). In contrast, the binding of the K417N mutant to Sb16 effectively maintains the salt bridge between LYS32 and GLU484. Therefore, our research suggests that the salt bridges between RBD and synthetic nanobodies are crucial for binding synthetic nanobodies to RBD, and a SARS-CoV-2 variant can escape neutralization from nanobodies by creating electrostatic repulsion between them.

Designing flower-like MOFs-derived N-doped carbon nanotubes encapsulated magnetic NiCo composites with multi-heterointerfaces for efficient electromagnetic wave absorption.

In order to acquire exceptional electromagnetic wave absorption properties, the microstructure design and component modification of composites are essential. Metal-organic frameworks (MOFs), due to the unique metal-organic crystalline coordination, tunable morphology, high surface area, and well-defined pores, have been regarded as promising electromagnetic wave absorption materials precursors. However, the inadequate contact abilities between adjacent MOFs nanoparticles endow it with undesirable electromagnetic wave dissipation capacity at a low filler loading, which is a great challenge to break size effect of nanoparticles to achieve efficient absorption. Herein, NiCo-MOFs derived N-doped carbon nanotubes encapsulated with NiCo nanoparticles anchored on flowers-like composites (denoted as NCNT/NiCo/C) were successfully prepared through facile hydrothermal method followed by thermal chemical vapor deposition with melamine-assisted catalyst. By controlling the Ni/Co ratio in precursor, the tunable morphology and microstructure of MOFs are achieved. Most importantly, the derived N-doped carbon nanotubes tightly connect the adjacent nanosheets to construct the special 3D interconnected conductive network, which effectively accelerates the charge transfer and improves the conduction loss. And notably, the NCNT/NiCo/C composite delivers excellent electromagnetic wave absorption performance with minimum reflection loss of -66.1 dB and wide effective absorption bandwidth up to 4.64 GHz when the Ni/Co ratio is 1:1. This work provides a novel method for the preparation of morphology controllable MOFs-derived composites and realizes high-performance electromagnetic wave absorption properties.

Corrosion-controlled surface engineering improves the adhesion of materials for stable free-standing electrodes.

Directly anchoring active materials on porous conductive substrates is considered an effective strategy to obtain a high-activity electrode since the direct contact between active materials and substrates benefits charge transfer, and the presence of porous structures provides more active sites. However, due to the presence of strong stress and weak adhesion, active materials loaded on the substrate are very easy to peel off during assembly and use, which can greatly shorten the lifetime of use. Herein, an ultrasonic corrosion strategy is proposed to regulate the surface of a metal substrate. We find that ultrasonic oxygen corrosion and interfacial water control play key roles in fabricating the complex electrode, which can help the surface of Cu foam to form special lamellar cross-linked CuO nanoarchitectures with strong adhesion and then overcome the defect of the deposited NiCo layered double hydroxides (NC LDH) on the stress and adhesion. The expected electrode shows more than 70% improvement in cycling stability at an ultra-high current density of 20 A g-1, relative to the active material layer of the electrode with strong stress and weak adhesion. Meanwhile, benefiting from its lamellar cross-linked nanoarchitectures having large specific surface area and many nano-pores, it presents a high specific capacitance of 3010.8F g-1 at 1 A g-1 and a good rate capability of 59.3% at 50 A g-1. It is foreseen that this finding provides a novel, universal strategy for managing the surface and interface of the metal substrate, thereby obtaining a reliable, stable electrode.

Adsorption of Organic Molecules and Surfactants on Graphene: A Coarse-Grained Study.

The research studies on the adsorption of surfactants on graphene help us to know how to use surfactants to exfoliate graphene from graphite or functionalize the graphene surface. Among them, molecular dynamics (MD) simulation has been widely used to investigate the adsorption of organic molecules and surfactants on graphene. In particular, coarse-grained (CG) MD simulation greatly improves the computational efficiency by simplifying the complexity of the studied systems, allowing us to explore the structure and dynamics of complex systems on larger spatial scales and longer time scales. However, an accurate prediction of the adsorption of surfactants on graphene is required by optimizing the interaction between surfactants and graphene, which is often overlooked by some CG models. In this work, we found that an accurate prediction of the adsorption enthalpies of organic molecules on graphene can be achieved by optimizing the interactions between organic molecules and benzene. Meanwhile, we simulated the adsorption of a surfactant on single-layer and double-layer graphene nanosheets, respectively. Our results revealed that increasing the temperature would favor the interactions between hydrophilic groups of surfactants. In addition, we discovered that the surfactant prefers to be adsorbed on the inner surfaces of double-layer graphene compared with the outer surfaces, and this is owing to the dehydration in the middle of double-layer graphene, which is beneficial to the hydrophilic interactions between surfactant molecules inside the double-layer graphene.

An ultra-effective pathway for fully removing the oxygen components of graphene oxide by a flame-assisted microwave process.

Here we report an ultra-effective and reliable pathway to reduce GO into graphene by an about 4 seconds flame-assisted microwave process. A holey graphene with a C/O atom ratio of 31.1, a pore volume of 6.0 cm3 g-1, and a specific surface area of 1050.0 m2 g-1 was synthesized.

Effect of Cholesterol and 6-Ketocholestanol on Membrane Dipole Potential and Sterol Flip-Flop Motion in Bilayer Membranes.

A variety of experimental and theoretical approaches have been employed to investigate the sterol flip-flop motion in lipid bilayer membranes. However, the sterol effect on the dipole potential of lipid bilayer membranes is less well studied and the influence of dipole potential on sterol flip-flop motion in lipid bilayer membranes is less well understood. In our previous works, we have demonstrated the performance of our coarse-grained (CG) model in the computation of the dipole potential. In this work, five 30 µs CG simulations of dimyristoylphosphatidylcholine (DMPC) bilayers were carried out at different sterol concentrations (in a range from 10 to 50% mole fraction). Then, a comparison was made between the effects of cholesterol (CHOL) and 6-ketocholestanol (6-KC) on the dipole potential of DMPC lipid bilayers as well as the sterol flip-flop motion. Our CG simulations show that the membrane dipole potential is impacted more significantly by 6-KC than by CHOL. This finding is consistent with recent experimental studies. Meanwhile, our work suggests that the sterol-sterol interactions (in particular, electrostatic interactions) should be critical to the formation of sterol-sterol clusters, which would hinder the sterol flip-flop motion inside the lipid bilayers. This is in support of the recent experimental study on the sterol transportation in lipid bilayer membranes.

Immunotherapy of tumor with vaccine based on basic fibroblast growth factor-activated fibroblasts.

PURPOSE: Cancer-associated fibroblasts play a key role in tumor progression. It is conceivable that the breaking of immune tolerance of "self-antigens" associated with tumor cells and tumor stromal is an attractive approach for tumor immunotherapy. To test this concept, we used basic fibroblast growth factor (bFGF) to activate normal fibroblasts and used these activated fibroblasts as one vaccine against tumor. METHODS: Normal fibroblasts were treated with bFGF; their expressions of a-SMA and FAP were assessed by Western blot. We immunized mice with bFGF-activated fibroblasts. Auto-antibodies were assessed by flow cytometric and Western blot analysis. The deposition of auto-antibodies within the tumor tissues was assessed. The inhibition of proliferation of tumor cells and fibroblasts by purified immunoglobulins was investigated. The anti-tumor effects of purified immunoglobulins and lymphocytes of immunized mice were assessed. RESULTS: The bFGF-activated fibroblasts were effective in affording protection from tumor onset, growth, and prolonging survival of tumor-bearing mice. The immunized sera exhibited positive staining for fibroblasts and tumor cells in FCAS and Western blot analysis. The purified immunoglobulins of immunized serum could inhibit the proliferation of tumor cells and fibroblasts in vitro and had the anti-tumor activity in vivo. There was the deposition of auto-antibodies within the tumor tissues. Adoptive transfer of lymphocytes of immunized mice revealed that cellular immune response is also involved. The anti-tumor activity could be abrogated by the depletion of CD4(+), CD8(+) T lymphocytes and NK cells. CONCLUSIONS: In summary, bFGF-activated fibroblasts could induce an autoimmune response which was simultaneously against both cancer-associated fibroblasts and tumor cells in a cross-reaction.