Phase-amplitude coupling of Go/Nogo task-related neuronal oscillation decreases for humans with insufficient sleep.

Phase-amplitude coupling (PAC) across frequency might be associated with the long-range synchronization of brain networks, facilitating the spatiotemporal integration of multiple cell assemblies for information transmission during inhibitory control. However, sleep problems may affect these cortical information transmissions based on cross-frequency PAC, especially when humans work in environments of social isolation. This study aimed to evaluate changes in the theta-beta/gamma PAC of task-related electroencephalography (EEG) for humans with insufficient sleep. Here, we monitored the EEG signals of 60 healthy volunteers and 18 soldiers in the normal environment, performing a Go/Nogo task. Soldiers also participated in the same test in isolated cabins. These measures demonstrated theta-beta PACs between the frontal and central-parietal, and robust theta-gamma PACs between the frontal and occipital cortex. Unfortunately, these PACs significantly decreased when humans experienced insufficient sleep, which was positively correlated with the behavioral performance of inhibitory control. The evaluation of theta-beta/gamma PAC of Go/Nogo task-related EEG is necessary to help understand the different influences of sleep problems in humans.

Association of plasma neutrophil gelatinase-associated lipocalin and thoracic aorta calcification in maintenance hemodialysis patients with and without diabetes.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. METHODS: Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. RESULTS: Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value(R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex (R = 0.550, P = 0.015), adjusting for age, sex and CHD (R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb (R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) (R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca (R = 0.644, P < 0.001), Ca and ACR (R = 0.534, P = 0.013) in Spearman coefficient analysis. CONCLUSION: There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.

Screening, simulation, and optimization design of small molecule inhibitors of the SARS-CoV-2 spike glycoprotein.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency of international concern. The spike glycoprotein (S protein) of SARS-CoV-2 is a key target of antiviral drugs. Focusing on the existing S protein structure, molecular docking was used in this study to calculate the binding energy and interaction sites between 14 antiviral molecules with different structures and the SARS-CoV-2 S protein, and the potential drug candidates targeting the SARS-CoV-2 S protein were analyzed. Tizoxanide, dolutegravir, bictegravir, and arbidol were found to have high binding energies, and they effectively bind key sites of the S1 and S2 subunits, inhibiting the virus by causing conformational changes in S1 and S2 during the fusion of the S protein with host cells. Based on the interactions among the drug molecules, the S protein and the amino acid environment around the binding sites, rational structure-based optimization was performed using the molecular connection method and bioisosterism strategy to obtain Ti-2, BD-2, and Ar-3, which have much stronger binding ability to the S protein than the original molecules. This study provides valuable clues for identifying S protein inhibitor binding sites and the mechanism of the anti-SARS-CoV-2 effect as well as useful inspiration and help for the discovery and optimization of small molecule S protein inhibitors.

Conformers, properties, and docking mechanism of the anticancer drug docetaxel: DFT and molecular dynamics studies.

The conformational structures and properties of the anticancer drug docetaxel (DTX) are studied theoretically. A total of 3888 trial structures were initially generated by all combinations of internal single-bond rotamers and screened with the B3LYP/3-21G* method. A total of 31 unique conformers were further optimized at the B3LYP/6-311G* method. Their relative energies, dipole moments, rotational constants, and harmonic vibrational frequencies were predicted. Single-point relative energies were then determined at the M06-L/6-311G(2df,p) level. The UV spectrum of the lowest-lying DTX conformer in methanol was investigated with the TD-CAM-B3LYP/6-311 + G(2df,p) method. The 31 unique DTX structures are mainly docked at three different sites within ß-tubulin. Based on the results of molecular docking and double-float MD simulations, the lowest-lying DTX conformer consistently exhibits good docking performance with ß-tubulin. We identified the residues LYS299, ARG215, GLN294, LEU275, THR216, GLU290, PRO274, and THR276 on ß-tubulin as active sites forming a binding pocket responsible for locking DTX within ß-tubulin to make the combination more stable. The RMSD values show that the predicted complexes are favorable, and the SASA analysis shows that the hydrophilic properties of DTX are better than paclitaxel. © 2018 Wiley Periodicals, Inc.