Assembly of Amyloid β Peptides in the Presence of Fibril Seeds: One-Pot Coarse-Grained Molecular Dynamics Simulations

The identification of a secondary nucleation pathway in the early aggregation of amyloid peptides suggests that the generation of toxic oligomers involves both monomers and preformed fibril seeds. To elucidate the underlying molecular mechanism, a set of one-pot coarse-grained molecular dynamics simulations was performed to investigate the self-assembly of amyloid β peptides in the presence of fibril seeds. It was observed that fibril seeds alone randomly assemble into an elongated protofibril, whereas monomers alone form an elongated globular oligomer with various morphologies. In the mixture of monomers and fibril seeds, both the self-assembly of monomers into small oligomers and the association of monomers and oligomers on the surface of fibril seeds are primarily driven by hydrophobic interactions. The cooperativity of conformational selection and competition leads to different binding propensity of two hydrophobic surfaces of fibril seeds. The molecular architecture of the final aggregate shows that the fibril seeds establish the elongated framework, and oligomers cover them. Oligomers exposed to the solvent are less compact and unstable and can be disassociated from the fibril seeds, providing an origin for oligomers generated from the secondary nucleation pathway

Exploring the Mechanism of Fluorescence Quenching and Aggregation-Induced Emission of a Phenylethylene Derivative by QM (CASSCF and TDDFT) and ONIOM (QM:MM) Calculations

We report a QM (including TD-DFT and CASSCF) and ONIOM (QM:MM) study on the fluorescence quenching in methanol solution and fluorescence enhancement in crystal for a styrene derivative, namely 4-diethylamino-2 benzylidene malonic acid dimethyl ester (BIM) that possesses push–pull structure and AIE properties. The results showed that in methanol solution the weakening of ethylenic CC bond after photoexcitation initiates a barrierless relaxation via one-bond rotation around it, until the reactive molecule reaches a low-energy intermediate with strong charge-transfer character, then a S₁/S₀ conical intersection optimized near the charge-transfer intermediate is responsible for the fluorescence quenching in the dilute solution. The existences of charge-transfer intermediate as well as the conical intersection in the vicinity, which has not been observed in other symmetric (or less polar) phenylethylene-based luminophores, are the major features of BIM in solution. While in crystalline phase, the excited-state deactivation channels via torsional motions, either via one-bond rotation or via hula-twist mechanism, are restricted by steric hindrance and electrostatic repulsion from surrounding molecules, and thus fluorescence is enhanced

Physicochemical properties of JS@GO nanofluid and its potential in enhanced oil recovery

Employing nanofluid flooding as an advanced enhanced oil recovery (EOR) technique has emerged as a groundbreaking approach for the extraction of residual hydrocarbons from increasingly depleted reservoirs. The innovative utilization of nanocomposites, specifically Janus SiO2 (JS) particles amalgamated with graphene oxide (GO), constitutes the focus of this research. We elucidate how this novel JS@GO nanocomposite enhances oil displacement through its exemplary interfacial activity, substantiated by various empirical evaluations such as contact angle and interfacial tension tests. Moreover, core flooding experiments corroborate the nanocomposite’s superior efficiency in augmenting oil recovery vis-a-vis traditional methodologies, which was due to the improvement of both emulsifying ability and amphiphilicity. The results of this research underscore the considerable promise the JS@GO nanofluid holds for future EOR applications, providing a compelling alternative for revitalizing oil production from heretofore unyielding reservoirs. Nanofluid flooding is recognized as an innovative EOR technique for residual oil. A novel JS@GO nanocomposite was successfully synthesized for EOR application. Interfacial activity of JS@GO was assessed using contact angle and IFT tests. Core flooding experiments underscore JS@GO nanofluid’s superior oil recovery capability. </p

Highly Crystalline Forms of Valsartan with Superior Physicochemical Stability

Single crystal structures of blockbuster antihypertensive drug Valsartan are revealed the first time in this report. Two new highly crystalline forms, named form E and an ethanol solvate form F, were discovered and fully characterized by PXRD, Raman, IR, TG, DSC, and DVS. Conformational flexibility and single crystal structures are discussed in detail. Physicochemical properties, such as hygroscopicity, chemical stability, crystallinity, and dissolution behaviors, are compared with the marketed solid-state form (amorphous state). The results show that the newly discovered highly crystalline form E presents a remarkably different dissolution behavior and superior chemical stability

Highly Crystalline Forms of Valsartan with Superior Physicochemical Stability

Single crystal structures of blockbuster antihypertensive drug Valsartan are revealed the first time in this report. Two new highly crystalline forms, named form E and an ethanol solvate form F, were discovered and fully characterized by PXRD, Raman, IR, TG, DSC, and DVS. Conformational flexibility and single crystal structures are discussed in detail. Physicochemical properties, such as hygroscopicity, chemical stability, crystallinity, and dissolution behaviors, are compared with the marketed solid-state form (amorphous state). The results show that the newly discovered highly crystalline form E presents a remarkably different dissolution behavior and superior chemical stability

Effect of dexamethasone (DEX, 100 μM for 36 h) treatment on mTOR, p70S6K, and IGF-I expression in C2C12 cells.

<p>p-mTOR protein levels (A), p-p70S6K (B), and IGF-I mRNA level (C). The values are presented as the means ± SEM (n = 6). ^a,b Means with different letters differ significantly (<i>P <</i> 0.05).</p

MOF-Derived Noble Metal Free Catalysts for Electrochemical Water Splitting

Noble metal free electrocatalysts for water splitting are key to low-cost, sustainable hydrogen production. In this work, we demonstrate that metal–organic frameworks (MOFs) can be controllably converted into catalysts for the oxygen evolution reaction (OER) or the hydrogen evolution reaction (HER). The OER catalyst is composed of FeNi alloy nanoparticles encapsulated in N-doped carbon nanotubes, which is obtained by thermal decomposition of a trimetallic (Zn²⁺, Fe²⁺, and Ni²⁺) zeolitic imidazolate framework (ZIF). It reaches 10 mA cm^–2 at the overpotential of 300 mV with a low Tafel slope of 47.7 mV dec^–1. The HER catalyst consists of Ni nanoparticles coated with a thin layer of N-doped carbon. It is obtained by thermal decomposition of a Ni-MOF in NH₃. It shows low overpotential of only 77 mV at 20 mA cm^–2 with low Tafel slope of 68 mV dec^–1. The above noble metal free OER and HER electrocatalysts are applied in an alkaline electrolyzer driven by a commercial polycrystalline solar cell. It achieves electrolysis efficiency of 64.4% at 65 mA cm^–2 under sun irradiation of 50 mW cm^–2. This practical application shows the promising prospect of low-cost and high-efficiency sustainable hydrogen production from combination of solar cells with high-performance noble metal free electrocatalysts

Effect of dexamethasone (DEX) on myostatin expression.

<p>Myostatin protein levels (A) and mRNA levels (B) in C2C12 cells treated with dexamethasone (DEX, 100 μM) for 12 h, 24 h, 36 h and 48 h. The values are presented as the means ± SEM (n = 6). ^a,b Means with different letters differ significantly (<i>P <</i> 0.05).</p

Effect of dexamethasone (DEX) treatment on the expression of ubiquitin-proteasome-related factors involved with protein catabolism.

<p>The total FoxO1 protein (A), phospho-FoxO1/3a (Thr 24/32) (B), FoxO1 and FoxO3 mRNA levels (C), MuRF1 protein (D), MuRF1 mRNA (E), atrogin-1 protein (F), and atrogin-1 mRNA (G) in C2C12 cells treated with DEX (100 μM) for 36 h. The values are presented as the means ± SEM (n = 6). ^a,b Means with different letters differ significantly (<i>P <</i> 0.05).</p

Effect of follistatin on protein synthesis and activation of mTOR/p70S6K pathway in C2C12 cells treated with dexamethasone (DEX, 100 μM for 36 h).

<p>The changes in protein synthesis rate (A) and phospho-mTOR (Ser 2448) (B) and phospho-p70S6K (C) levels in C2C12 cells after treatment with DEX (100 μM) and follistatin (800 ng/ml) for 36 h. The values are presented as the means ± SEM (n = 6). ^a,b Means with different letters differ significantly (<i>P <</i> 0.05).</p