Impairment of delayed recall as a predictor of amnestic mild cognitive impairment development in normal older adults: a 7-year of longitudinal cohort study in Shanghai.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered a prodromal phase of Alzheimer's disease (AD). However, little is known about the neuropsychological characteristic at pre-MCI stage. This study aimed to investigate which neuropsychological tests could significantly predict aMCI from a seven-year longitudinal cohort study. METHODS: The present study included 123 individuals with baseline cognitive normal (NC) diagnosis and a 7-year follow-up visit. All the subjects were from the China Longitudinal Aging Study (CLAS) study. Participants were divided into two groups, non-converter and converter based on whether progression to aMCI at follow-up. All participants underwent standardized comprehensive neuropsychological tests, including the mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), auditory verbal learning test (AVLT), the digital span test, the verbal fluency test, the visual recognition test, the WAIS picture completion task, and WAIS block design. Logistic regression analysis was used to evaluate the predictive power of baseline cognitive performance for the transformation of amnestic mild cognitive impairment. Receiver operating characteristic (ROC) curve was used to test the most sensitive test for distinguishing different groups. RESULTS: Between the non-converter group and converter group, there were significant differences in the baseline scores of AVLT-delayed recall (AVLT-DR) (8.70 ± 3.61 vs. 6.81 ± 2.96, p = 0.001) and WAIS block design (29.86 ± 7.07 vs. 26.53 ± 8.29, p = 0.041). After controlling for gender, age, and education level, converter group showed lower baseline AVLT-DR than non-converter group, while no significant difference was found in WAIS block design. Furthermore, converter group had lower AVLT-DR score after controlling for somatic disease. The area under the curve of regression equation model was 0.738 (95%CI:0.635-0.840), with a sensitivity 83.9%, specificity of 63.6%. CONCLUSIONS: Our results proved the value of delayed recall of AVLT in predicting conversion to aMCI. Early and careful checking of the cognitive function among older people should be emphasized.

Lattice Deformation of Tb0.29Dy0.71Fe1.95 Alloy during Magnetization.

In Tb-Dy-Fe alloy systems, Tb0.29Dy0.71Fe1.95 alloy shows giant magnetostrictive properties under low magnetic fields, thus having great potential for transducer and sensor applications. In this work, the lattice parameters of Tb0.29Dy0.71Fe1.95 compounds as a function of a magnetic field were investigated using in situ X-ray diffraction under an applied magnetic field. The results showed that the c-axis elongation of the rhombohedral unit cell was the dominant contributor to magnetostriction at a low magnetic field (0-500 Oe). As the magnetic field intensity increased from 500 Oe to 1500 Oe, although the magnetostrictive coefficient continued to increase, the lattice constant did not change, which indicated that the elongated c-axis of the rhombohedral unit cell rotated in the direction of the magnetic field. This rotation mainly contributed to the magnetostriction phenomenon at magnetic fields of above 500 Oe. The structural origin of the magnetostriction performance of these materials was attributed to the increase in rhombohedral lattice parameters and the rotation of the extension axis of the rhombohedral lattice.

Variations in the Crystal Lattice of Tb-Dy-Fe Magnetostrictive Materials: The Lattice Constant Disturbance.

In Tb-Dy-Fe alloy systems, Tb0.29Dy0.71Fe1.95 alloy shows giant magnetostrictive properties under low magnetic fields, thus having great potential for transducers, microsensors, and other applications. The C15 cubic crystal structure of Tb-Dy-Fe has long been thought to be the source of giant magnetostriction. It is surprising that such a highly symmetrical crystal structure exhibits such a large magnetostrictive strain. In this work, the lattice parameters of Tb0.29Dy0.71Fe1.95 magnetostrictive materials were studied by processing atomic-resolution images. The selected area diffraction patterns show a face-centered cubic structure, but the fast Fourier transform diagram shows that the cubic structure has obvious distortion. The lattice parameters obtained by geometric phase analysis (GPA) and Gaussian model-based fitting and calculation show that the lattice constants a, b, and c are not strictly equal, and small disturbance of the lattice constants occurs based on the cubic structure. The actual crystal structure of the Tb-Dy-Fe material is a slightly disturbed cubic structure. This variation in the crystal lattice is mainly caused by the inhomogeneous composition and may be related to the giant magnetostrictive properties of Tb-Dy-Fe alloy.

Discovery of a Potent and Orally Bioavailable Hypoxia-Inducible Factor 2α (HIF-2α) Agonist and Its Synergistic Therapy with Prolyl Hydroxylase Inhibitors for the Treatment of Renal Anemia.

Activation of hypoxia-inducible factor 2 (HIF-2) has emerged as a potent renal anemia treatment strategy. Here, the benzisothiazole derivative 26 was discovered as a novel HIF-2α agonist, which first demonstrated nanomolar activity (EC50 = 490 nM, Emax = 349.2%) in the luciferase reporter gene assay. Molecular dynamics simulations indicated that 26 could allosterically enhance HIF-2 dimerization. Furthermore, compound 26 had a good pharmacokinetic profile (the oral bioavailability in rats was 41.38%) and an in vivo safety profile (the LD50 in mice was greater than 708 mg·kg-1). In the in vivo efficacy assays, the combination of 26 and the prolyl hydroxylase inhibitor, AKB-6548, was confirmed for the first time to synergistically increase the plasma erythropoietin level in mice (from 260 to 2296 pg·mL-1) and alleviate zebrafish anemia induced by doxorubicin. These results provide new insights for HIF-2α agonists and the treatment of renal anemia.