Self-Assembly Behavior and Application of Terphenyl-Cored Trimaltosides for Membrane-Protein Studies: Impact of Detergent Hydrophobic Group Geometry on Protein Stability

Amphipathic agents are widely used in various fields including biomedical sciences. Micelle-forming detergents are particularly useful for in vitro membrane-protein characterization. As many conventional detergents are limited in their ability to stabilize membrane proteins, it is necessary to develop novel detergents to facilitate membrane-protein research. In the current study, we developed novel trimaltoside detergents with an alkyl pendant-bearing terphenyl unit as a hydrophobic group, designated terphenyl-cored maltosides (TPMs). We found that the geometry of the detergent hydrophobic group substantially impacts detergent self-assembly behavior, as well as detergent efficacy for membrane-protein stabilization. TPM-Vs, with a bent terphenyl group, were superior to the linear counterparts (TPM-Ls) at stabilizing multiple membrane proteins. The favorable protein stabilization efficacy of these bent TPMs is likely associated with a binding mode with membrane proteins distinct from conventional detergents and facial amphiphiles. When compared to n-dodecyl-β-d -maltoside (DDM), most TPMs were superior or comparable to this gold standard detergent at stabilizing membrane proteins. Notably, TPM-L3 was particularly effective at stabilizing the human β₂ adrenergic receptor (β₂AR), a G-protein coupled receptor, and its complex with G_s protein. Thus, the current study not only provides novel detergent tools that are useful for membrane-protein study, but also suggests a critical role for detergent hydrophobic group geometry in governing detergent efficacy.     

A Near-Infrared-Controllable Artificial Metalloprotease Used for Degrading Amyloid-β Monomers and Aggregates

Proteolysis of amyloid-β (Aβ) is a promising approach against Alzheimer's disease. However, it is not feasible to employ natural hydrolases directly because of their cumbersome preparation and purification, poor stability, and hazardous immunogenicity. Therefore, artificial enzymes have been developed as potential alternatives to natural hydrolases. Since specific cleavage sites of Aβ are usually embedded inside the β-sheet structures that restrict access by artificial enzymes, this strongly hinders their efficiency for practical applications. Herein, we construct a NIR (near-IR) controllable artificial metalloprotease (MoS₂-Co) using a molybdenum disulfide nanosheet (MoS₂) and a cobalt complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Codota). Evidenced by detailed experimental and theoretical studies, the NIR-enhanced MoS₂-Co can circumvent the restriction by simultaneously inhibition of β-sheet formation and destroying β-sheet structures of the preformed Aβ aggregates in living cell. Furthermore, our designed MoS₂-Co is an easy to graft Aβ-target agent that prevents misdirected or undesirable hydrolysis reactions, and has been demonstrated to cross the blood brain barrier. This method can be adapted for hydrolysis of other kinds of amyloids.     

Lewis Acid Transition-Metal-Catalyzed Hydrogen Activation: Structures,Mechanisms, and Reactivities

As a new type of bifunctional catalyst, the Lewis acid transition-metal (LA-TM) catalysts have been widely applied for hydrogen activation. This study presents a mechanistic framework to understand the LA-TM-catalyzed H₂ activation through DFT studies. The mer(trans)-homolytic cleavage, the fac(cis)-homolytic cleavage, the synergetic heterolytic cleavage, and the dissociative heterolytic cleavage should be taken as general mechanisms for the field of LA-TM catalysis. Four typical LA-TM catalysts, the Z-type κ⁴-L₃B-Rh complex tri(azaindolyl)borane-Rh, the X-type κ³-L₂B-Co complex bis-phosphino-boryl (PBP)-Co, the η²-BC-type κ³-L₂B-Pd complex diphosphine-borane (DPB)-Pd, and the Z-type κ²-LB-Pt complex (boryl)iminomethane (BIM)-Pt are selected as representative models to systematically illustrate their mechanistic features and explore the influencing factors on mechanistic variations. Our results indicate that the tri(azaindolyl)borane-Rh catalyst favors the synergetic heterolytic mechanism; the PBP-Co catalyst prefers the mer(trans)-homolytic mechanism; the DPB-Pd catalyst operates through the fac(cis)-homolytic mechanism, whereas the BIM-Pt catalyst tends to undergo the dissociative heterolytic mechanism. The mechanistic variations are determined by the coordination geometry, the LA-TM bonding nature, the electronic structure of the TM center, and the flexibility or steric effect of the LA ligands. The presented mechanistic framework should provide helpful guidelines for LA-TM catalyst design and reaction developments.     

Hydrogen-Bond Cyclization Programming of Ultrasensitive Esters and Its Application in Gene Delivery

The ester bond as a universal linker has recently been applied in gene delivery systems owing to its efficient gene release by electrostatic repulsion after its cleavage. However, the ester bond is nonlabile and is difficult to cleave in cells. This work reports a method in which a secondary amine was introduced to the β-position of the ester bond to generate a hydrogen-bond cyclization (HBC) structure that can make the ester bond hydrolysis ultrafast. A series of molecules comprising ultrasensitive esters that can be activated by H₂O₂ were synthesized, and it was found that those able to form an HBC structure showed complete ester hydrolysis within 5 h in both water and phosphate-buffered saline solution, which was several times faster than other methods reported. Then, a series of amphiphilic poly(amidoamine) dendrimers were constructed, comprising the ultrasensitive ester groups for gene delivery; it was found that they could effectively release genes under quite a low concentration of H₂O₂ (<200 μm ) and transport them into the nucleus within 2 h in Hela cells with high safety. Their gene transfection efficiencies were higher than that of PEI_25k. The results demonstrated that the hydrogen-bond-induced ultrasensitive esters could be powerfully applied to construct gene delivery systems.     

Non-isothermal thermogravimetric analysis of pyrolysis kinetics of four oil shales using Sestak–Berggren method

Journal of Thermal Analysis and Calorimetry - In this study, the non-isothermal pyrolysis method was used to investigate the pyrolysis characteristics of oil shale from four areas: namely Nongan,...     

Impact Force Identification on Carbon Fibre–Epoxy Honeycomb Composite Panel Based on Local Convex Curve Criterion

Experimental Mechanics - Identification of impact force is essential for various engineering applications, such as performance evaluation, design optimisation, noise suppression, and vibration...     

Rhodium-Catalyzed Remote C(sp3)−H Borylation of Silyl Enol Ethers

A rhodium-catalyzed remote C(sp³)−H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional-group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n-borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n-diols and aminoalcohols.     

Electrical properties of Ca3-xSmxCo4O9+δceramics prepared under magnetic field

We fabricate Sm-doped Ca3Co4O9+δ(CCO)bulk materials in magnetic field during both processes of chemical synthesis and cold pressing.The structure and electrical performance of the samples are investigated.With the increasing Sm concentration,the electrical conductivity 1/ρ decreases and the Seebeck coefficientαincreases.As a result,the power factor(PF=α^2/ρ)is raised slightly.After applying magnetic field,the extent of texture,grain size and density of all the bulk materials are improved obviously,thereby an enhanced electrical conductivity can be gained.Additionally,the degeneracy of Co^4+ state in the CoO2 layer of CCO is also increased as the magnetic field is used in the preparing process,which results in an enhancedα.The Ca2.85Sm0.15Co4O9+δ prepared in magnetic field shows the largest power factor(0.20 mW·m^-1·K^-2 at 1073 K).     

Camptothecin@HMSNs/thermosensitive hydrogel composite for applications in preventing local breast cancer recurrence

The CPT was loaded into the HMSNs with the high loading capacity. Then the CPT@HMSNs were loaded into the PLEL thermosensitive hydrogels for local therapy to prevent the recurrence of breast cancer after the tumor was resected.