Supramolecular Hydrolase Mimics in Equilibrium and Kinetically Trapped States.

The folding of proteins into intricate three-dimensional structures to achieve biological functions, such as catalysis, is governed by both kinetic and thermodynamic controls. The quest to design artificial enzymes using minimalist peptides seeks to emulate supramolecular structures existing in a catalytically active state. Drawing inspiration from the nuanced process of protein folding, our study explores the enzyme-like activity of amphiphilic peptide nanosystems in both equilibrium and non-equilibrium states, featuring the formation of supramolecular nanofibrils and nanosheets. In contrast to thermodynamically stable nanosheets, the kinetically trapped nanofibrils exhibit dynamic characteristics (e.g., rapid molecular exchange and relatively weak intermolecular packing), resulting in a higher hydrolase-mimicking activity. We emphasize that a supramolecular microenvironment characterized by an optimal local polarity, microviscosity, and ß-sheet hydrogen bonding is conducive to both substrate binding and ester bond hydrolysis. Our work underscores the pivotal role of both thermodynamic and kinetic control in impacting biomimetic catalysis and sheds a light on the development of artificial enzymes.

The role of halogens in Au-S bond cleavage for energy-differentiated catalysis at the single-bond limit.

The transformation from one compound to another involves the breaking and formation of chemical bonds at the single-bond level, especially during catalytic reactions that are of great significance in broad fields such as energy conversion, environmental science, life science and chemical synthesis. The study of the reaction process at the single-bond limit is the key to understanding the catalytic reaction mechanism and further rationally designing catalysts. Here, we develop a method to monitor the catalytic process from the perspective of the single-bond energy using high-resolution scanning tunneling microscopy single-molecule junctions. Experimental and theoretical studies consistently reveal that the attack of a halogen atom on an Au atom can reduce the breaking energy of Au-S bonds, thereby accelerating the bond cleavage reaction and shortening the plateau length during the single-molecule junction breaking. Furthermore, the distinction in catalytic activity between different halogen atoms can be compared as well. This study establishes the intrinsic relationship among the reaction activation energy, the chemical bond breaking energy and the single-molecule junction breaking process, strengthening our mastery of catalytic reactions towards precise chemistry.

Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells.

Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.

Metal organic complexes as an artificial solid-electrolyte interface with Zn-ion transfer promotion for long-life zinc metal batteries.

Metal organic complexes as an artificial solid-electrolyte interface (MOC-SEI) have been generated via in situ coordinative polymerization between Zn2+ and organic ligand molecules. Compared to conventional anodes, the MOC-SEI coated anode significantly prolongs the lifespan from 100 h to 1450 h for the Zn||Zn symmetrical cells and increases the reversible capacity up to 160 mA h g-1 after 1100 cycles for the Zn||V2O5 full-cells.

Synthetic Neutralizing Peptides Inhibit the Host Cell Binding of Spike Protein and Block Infection of SARS-CoV-2.

Antiviral treatments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been extensively pursued to conquer the pandemic. To inhibit the viral entry to the host cell, we designed and obtained three peptide sequences via quartz crystal microbalance measurement screening, which showed high affinity at nanomole to the S1 subunit of the spike protein and wild-type SARS-CoV-2 pseudovirus. Circular dichroism spectroscopy measurements revealed significant conformation changes of the S1 protein upon encounter with the three peptides. The peptides were able to effectively block the infection of a pseudovirus to 50% by inhibiting the host cell lines binding with the S1 protein, evidenced by the results from Western blotting and pseudovirus luciferase assay. Moreover, the combination of the three peptides could increase the inhibitory rate to 75%. In conclusion, the three chemically synthetic neutralizing peptides and their combinations hold promising potential as effective therapeutics in the prevention and treatment of COVID-19.