Mechanic Insight into Aggregation of Lysozyme by Ultrasensitive Differential Scanning Calorimetry and Sedimentation Velocity

Folding and aggregation of proteins profoundly influence their functions. We have investigated the effects of thermal history, concentration and pH on the denaturation and refolding of lysozyme by using ultrasensitive differential scanning calorimetry (US-DSC) and sedimentation velocity (SV) via analytical ultracentrifugation (AUC). The former is sensitive to small energy change whereas the latter can differentiate the oligomers such as dimer and trimer from individual protein molecules. Our studies reveal that the degree of denaturation irreversibility increases as heating times increases. The denaturation temperature (<i>T</i>_d) and enthalpy change (Δ<i>H</i>) are influenced by heating rate since the denaturation is not in equilibrium during the heating. We can obtain <i>T</i>_d and Δ<i>H</i> in equilibrium by extrapolation of heating rate to zero. In a dilute solution, no aggregation but unfolding happens in the denaturation. However, when the concentration is above a critical value (∼15.0 mg/mL), lysozyme molecules readily form trimers or other oligomers. Lysozyme molecules unfold into stretched chains at pH > 6.0, which would further forms large aggregates. The formation of aggregates makes the refolding of lysozyme impossible

Participant characteristics and the distributions of anxiety symptoms by categorical variable.

<p>Participant characteristics and the distributions of anxiety symptoms by categorical variable.</p

The mediating model: relationships between occupational stress and anxiety symptoms.

<p>β–coefficient above the line: without the mediation; β–coefficient below the line: with the mediation. * p<0.05, *** p<0.001.</p

Means, standard deviations (SD) and correlations of all variables.

<p>*p<0.05, **p<0.01 (two-tailed).</p><p>Means, standard deviations (SD) and correlations of all variables.</p

Hierarchical linear regression analysis results.

<p>*p<0.05, ** p<0.01, *** p<0.001 (two-tailed).</p><p>Hierarchical linear regression analysis results.</p

Mechanistic Insights into Amplification of Specific Ion Effect in Water–Nonaqueous Solvent Mixtures

Ethylene glycol (EG) and hydrogen peroxide (H₂O₂) can act as both hydrogen-bond donors and acceptors in the formation of solvent complexes with water molecules. In the present work, we have systematically investigated the ion-specific lower critical solution temperature (LCST) behavior of poly­(<i>N</i>-isopropylacrylamide) (PNIPAM) in H₂O–EG and H₂O–H₂O₂ mixtures. The results obtained from turbidity measurements show that the specific anion effect is amplified with the increasing molar fraction of EG (<i>x</i>_EG) but is independent of the molar fraction of H₂O₂ (<i>x</i>_H₂O₂). The studies of Raman spectra and differential scanning calorimetry indicate that the discrepancy in amplification of specific anion effect between H₂O–EG and H₂O–H₂O₂ mixtures is due to the difference in the anion–solvent complex interactions rather than the anion–polymer or solvent–polymer interactions. On the other hand, the specific cation effect can also be amplified with the increasing <i>x</i>_EG but changes only slightly with the <i>x</i>_H₂O₂. The discrepancy in amplification of specific cation effect between the two types of solvent mixtures is attributed to the difference in the solvent–polymer interactions

Multistep Thermosensitivity of Poly(<i>N</i>-<i>n</i>-propylacrylamide)-<i>block</i>-poly(<i>N</i>-isopropylacrylamide)-<i>block</i>-poly(<i>N</i>,<i>N</i>-ethylmethylacrylamide) Triblock Terpolymers in Aqueous Solutions As Studied by Static and Dynamic Light Scattering

Poly(N-n-propylacrylamide)-block-poly(N-isopropylacrylamide)-block-poly(N,N-ethylmethylacrylamide) (PnPA-b-PiPA-b-PEMA) triblock terpolymers of low polydispersity have been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization via sequential monomer addition. The temperature-induced formation and dissociation of terpolymer micelles in aqueous solutions in a heating−cooling cycle were investigated by a combination of static and dynamic laser light scattering. In the heating process, the folding of PnPA at ca. 25 °C led to the formation of polymeric micelles with a collapsed hydrophobic PnPA core and a hydrophilic swollen PiPA−PEMA shell. Further increase of the temperature to ca. 32 and 53 °C led to the successive dehydration of PiPA and PEMA on the periphery, respectively. Our results revealed that when PEMA on the periphery of the micelle is too short to stabilize the hydrophobic core, individual micelles tend to aggregate into large micellar clusters, corresponding to the intrachain contraction and interchain association of the PiPA chains. In the cooling process, the complete dissolution temperature was lower than the association temperature in the heating process. At a given temperature, the aggregates in the cooling process had a higher mass than those in the heating process, clearly indicating a hysteresis

Facile and High-Efficiency Chemical Presodiation Strategy on the SnS₂/rGO Composite Anode for Stable Sodium-Ion Batteries

SnS2/reduced graphite oxide (rGO) composite materials show great potential as high-performance anode candidates in sodium-ion batteries (SIBs) owing to their high specific capacities and power densities. However, the repeated formation/decomposition of the solid electrolyte interface (SEI) layer around composite anodes usually consumes additional sodium cations, resulting in poor Coulombic efficiency and decreasing specific capacity upon cycling. Therefore, in order to compensate for the large irreversible sodium loss of the SnS2/rGO anode, this study has proposed a facile strategy by implementing organic solutions of sodium-biphenyl/tetrahydrofuran (Na-Bp/THF) and sodium-naphthylamine/dimethoxyethane (Na-Naph/DME) as chemical presodiation reagents. Particularly, the storage stability of Na-Bp/THF and Na-Naph/DME in ambient air accompanied by their presodiation behavior on the SnS2/rGO anode has been investigated, and both reagents exhibited desirable ambient air-tolerant storage stability with favorable sodium supplement effects even after 20 days of storage. More importantly, the initial Coulombic efficiency (ICE) of SnS2/rGO electrodes could be controllably increased by immersing in a presodiation reagent for different durations. Consequently, with a facile chemical presodiation strategy of immersion in Na-Bp/THF solution for only 3 min in ambient air, the presodiated SnS2/rGO anode has exhibited an outstanding electrochemical performance with a high ICE of 95.6% as well as an ultrahigh specific capacity of 879.2 mAh g–1 after 300 cycles (83.5% of its initial capacity), highly superior to the pristine SnS2/rGO anode. This efficient and scalable presodiation strategy provides a new avenue for the prevailing application of other anode candidates in high-energy SIBs

Discovery of Imigliptin, a Novel Selective DPP‑4 Inhibitor for the Treatment of Type 2 Diabetes

We report our discovery of a novel series of potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from a lead identified by scaffold-hopping approach, our discovery and development efforts were focused on exploring structure–activity relationships, optimizing pharmacokinetic profile, improving <i>in vitro</i> and <i>in vivo</i> efficacy, and evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial