Carbon-Free, Binder-Free MnO₂@Mn Catalyst for Oxygen Reduction Reaction

Reasonable design and feasible preparation of low-cost and stable oxygen reduction reaction (ORR) catalysts with excellent performance play a key role in the development of fuel cells and metal–air batteries. A 3D porous superimposed nanosheet catalyst composed of metal manganese covered with MnO2 nanofilms (P-NS-MnO2@Mn) was designed and synthesized by rotating disk electrodes (RDEs) through one-step electrodeposition. The catalyst contains no carbon material. Therefore, the oxidation and corrosion of the carbon material during use can be avoided, resulting in excellent stability. The structural and composition characterizations indicate that the nanosheets with sharp edges exist on the surface of the wall surrounding the macropore (diameter ∼ 5.07 μm) and they connect tightly. Both the nanosheets and the wall of the macropore are composed of metal manganese covered completely with MnO2 film with a thickness of less than 5 nm. The half-wave potential of the synthesized P-NS-MnO2@Mn catalyst is 0.86 V. Besides, the catalyst exhibits good stability with almost no decay after a 30 h chronoamperometric test. Finite element analysis (FEA) simulation reveals the high local electric field intensity surrounding the sharp edges of the nanosheets. Density functional theory (DFT) calculations reveal that the novel nanosheet structure composed of MnO2 nanofilms covered on the surface of the Mn matrix accelerates the electronic transfer of the MnO2 nanofilms during the ORR process. The high local electric field intensity near the sharp edge of the nanosheets effectively promotes the orbital hybridization and strengthens the adsorbing Mn–O bond between the active site Mn in the nanosheets and the intermediate OOH* during the ORR process. This study provides a new strategy for preparing transition metal oxide catalysts and a novel idea about the key factors affecting the catalytic activity of transition metal oxides for the ORR

How Do Proteins Unfold upon Adsorption on Nanoparticle Surfaces?

Owing to their many outstanding features, such as small size, large surface area, and cell penetration ability, nanoparticles have been increasingly used in medicine and biomaterials as drug carriers and diagnostic or therapeutic agents. However, our understanding of the interactions of biological entities, especially proteins, with nanoparticles is far behind the explosive development of nanotechnology. In typical protein–nanoparticle interactions, two processes (i.e., surface binding and conformational changes in proteins) are intermingled with each other and have not yet been quantitatively described. Here, by using a stopped-flow fast mixing technique, we were able to shed light on the kinetics of the adsorption-induced protein unfolding on nanoparticle surfaces in detail. We observed a biphasic denaturation behavior of protein GB1 on latex nanoparticle surfaces. Such kinetics can be adequately described by a fast equilibrium adsorption followed by a slow reversible unfolding of GB1. On the basis of this model, we quantitatively measured all rate constants that are involved in this process, from which the free-energy profile is constructed. This allows us to evaluate the effects of environmental factors, such as pH and ionic strength, on both the adsorption and the conformational change in GB1 on the latex nanoparticle surface. These studies provide a general physical picture of the adsorption-induced unfolding of proteins on nanoparticle surfaces and a quantitative description of the energetics of each transition. We anticipate that it will greatly advance our current understanding of protein–nanoparticle interactions and will be helpful for the rational control of such interactions in biomedical applications

sj-doc-1-aim-10.1177_09645284211056657 – Supplemental material for Exploring the perceptions of the educational environment in online acupuncture learning during the COVID-19 pandemic

Supplemental material, sj-doc-1-aim-10.1177_09645284211056657 for Exploring the perceptions of the educational environment in online acupuncture learning during the COVID-19 pandemic by Huijuan Mao, Linang Wang, Meng Qin, Jianzi Wei and Sheng Liu in Acupuncture in Medicine</p

Mechanistic Insights into the Stabilization of srcSH3 by PEGylation

Protein PEGylation (attaching PEG chains to proteins) has been widely used in pharmaceuticals and nanotechnology. Although it is widely known that PEGylation can increase the thermodynamic stability of proteins, the underlying mechanism remains elusive. In this Article, we studied the effect of PEGylation on the thermodynamic and kinetic stability of a protein, SH3. We show that the thermodynamic stability of SH3 is enhanced upon PEGylation, mainly due to the slowing of the unfolding rate. Moreover, PEGylation can decrease the solvent-accessible surface area of SH3, leading to an increase of the m-value (the change in free energy with respect to denaturant concentration, which is a measure of the transition cooperativity between corresponding states). Such an effect also causes an enhancement of the thermodynamic stability. We quantitatively measured how the physical properties of PEG, such as the molecular weight and the number of PEGylation sites, affect the stabilization effect. We found that the stabilization effect is largely dependent on the number of PEGylation sites but only has a weak correlation with the molecular weight of the attached PEG. These experimental findings inspire us to derive a physical model based on excluded volume effect, which can satisfactorily describe all experimental observations. This model allows quantitatively calculating the free energy change upon PEGylation based on the change of water excluded zone on the protein surface. Although it is still unknown whether such a mechanism can be extended to other proteins, our work represents a key step toward the understanding of the nature of protein stabilization upon PEGylation

Photo-Cross-Linking Approach to Engineering Small Tyrosine-Containing Peptide Hydrogels with Enhanced Mechanical Stability

Peptide-based supramolecular hydrogels have been extensively explored in biomaterials owing to their unique bioactive, stimulus-responsive, and biocompatible features. However, peptide-based hydrogels often have low mechanical stability with storage moduli of 10–1000 Pa. They are susceptible to mechanical destruction and solvent erosion, greatly hindering their practical application. Here, we present a photo-cross-linking strategy to enhance the mechanical stability of a peptide-based hydrogel by 104-fold with a storage modulus of ∼100 kPa, which is one of the highest reported so far for hydrogels made of small peptide molecules. This method is based on the ruthenium-complex-catalyzed conversion of tyrosine to dityrosine upon light irradiation. The reinforcement of the hydrogel through photo-cross-linking can be achieved within 2 min thanks to the fast reaction kinetics. The enhancement of the mechanical stability was due to the formation of a densely entangled fibrous network of peptide dimers through a dityrosine linkage. We showed that in order to implement this method successfully, the peptide sequence should be rationally designed to avoid the cross talk between self-assembly and cross-linking. This method is convenient and versatile for the enhancement of the mechanical stability of tyrosine-containing peptide-based hydrogels. We anticipate that the photo-cross-linked supramolecular hydrogels with much improved mechanical stability will find broad applications in tissue engineering and drug controlled release

sj-tif-1-aim-10.1177_09645284211056657 – Supplemental material for Exploring the perceptions of the educational environment in online acupuncture learning during the COVID-19 pandemic

Supplemental material, sj-tif-1-aim-10.1177_09645284211056657 for Exploring the perceptions of the educational environment in online acupuncture learning during the COVID-19 pandemic by Huijuan Mao, Linang Wang, Meng Qin, Jianzi Wei and Sheng Liu in Acupuncture in Medicine</p

Dimerization of Cell-Adhesion Molecules Can Increase Their Binding Strength

Cell-adhesion molecules (CAMs) often exist as homodimers under physiological conditions. However, owing to steric hindrance, simultaneous binding of two ligands to the homodimers at the same location can hardly be satisfied, and the molecular mechanism underlying this natural design is still unknown. Here, we present a theoretical model to understand the rupture behavior of cell-adhesion bonds formed by multiple binding ligands with a single receptor. We found that the dissociation forces for the cell-adhesion bond could be greatly enhanced in comparison with the monomer case through a ligand rebinding and exchange mechanism. We also confirmed this prediction by measuring dimeric cRGD (cyclic Arg-Gly-Asp) unbinding from integrin (α_vβ₃) using atomic force microscopy-based single-molecule force spectroscopy. Our finding addresses the mechanism of increasing the binding strength of cell-adhesion bonds through dimerization at the single-molecule level, representing a key step toward the understanding of complicated cell-adhesion behaviors. Moreover, our results also highlight a wealth of opportunities to design mechanically stronger bioconjunctions for drug delivery, biolabeling, and surface modification

Hydrodynamic Force Depends Not Only on the Viscosity of Solution but Also on the Molecular Weights of Viscogens

Many cellular processes, such as the diffusion of biomacromolecules, the movement of molecular motors, and the conformational dynamics of proteins, are subjected to hydrodynamic forces because of the high viscosities of cellular environments. However, it is still unknown how hydrodynamic forces are related to the physical properties of different viscogens. Here, using the atomic force microscope-based force spectroscopy technique, we directly measured the hydrodynamic forces acting on a moving cantilever in various viscogen solutions. We found that the hydrodynamic force is not only dependent on the viscosity but also related to the molecular weight of viscogens. Counterintuitively, at the same macroscopic viscosity, the hydrodynamic force rises with the increasing molecular weight of viscogens, although the local microscopic viscosity of the solution decreases. This finding provides insights into the origin of hydrodynamic forces in biomolecule solutions and could inspire many force-spectroscopy-based techniques to measure the molecular weight and conformational changes of biomacromolecules in biological settings directly

Graphical table of contents.

An optimized formulation containing Albendazole-bile derivative (ABZ-BA) was developed, which significantly improved the pharmacokinetics and the anti-AE efficacy, after a 30-day, once-daily oral administration. (TIF)</p

A Versatile “Multiple Fishhooks” Approach for the Study of Ligand–Receptor Interactions Using Single-Molecule Atomic Force Microscopy

Despite the powerfulness of atomic force microscopy (AFM)-based single-molecule force spectroscopy in the study of ligand–receptor interactions, complicated cantilever functionalization and data interpretation have often been a great hurdle for its widespread application. Here, we present a much simplified experimental scheme by using a “multiple fishhooks” approach. In this strategy, multiple ligands are labeled on a single polymer chain, which forms complexes with receptors anchored on the substrate surface. Therefore, multiple single-bond rupture events can be captured in the same force–extension curves, similar to the widely used polyprotein approach. This method also allows nonsingle-molecule events and nonspecific interactions between cantilever and surface to be readily excluded from real data pool and greatly increases the quality and quantity of single-molecule data. The biggest advantage of our approach over the previously reported one is the choice of a naturally occurring polysaccharide, hyaluronan, the conformation of which in solution can be fine-tuned by pH, as the polymer backbone of the “multiple fishhooks” handle. Furthermore, our approach greatly simplifies the chemical synthesis of the polymer handle, allowing bioactive molecules to be easily one-step labeled on the handles in aqueous solution. We validate this strategy using the widely studied streptavidin–biotin system, and our single-molecule AFM results are in good agreement with previously reported ones. We anticipate that this novel strategy can be used as a versatile tool to study other complex and challenging ligand–receptor interactions