[Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro].

Objective: To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrPSc). Methods: The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrPSc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrPSc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results: CCK8 cell viability assay results demonstrated that treatment with 1 µmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 µmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 µmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrPSc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrPSc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10-6 mol/L. Conclusions: CAPE inhibits PrPSc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

[Expression and significance of serum insulin-like growth factor-1 in patients with obstructive sleep apnea hypopnea syndrome].

Objective:To investigate the expression and significance of serum insulinlike growth factor-1(IGF-1) in adult patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Method:One hundred and seven patients of OSAHS diagnosed with PSG were included in the observation group，which were divided into heavy, medium and light group according to AHI.Fifty case of healthy people without OSAHS were included in control group.Serum IGF-1 were measured by ELISA. Thirty patients of heavy OSAHS received surgery and CPAP treatment for three months,and were retested the levels of IGF-1 and PSG six months later.Result:①With the increase of OSAHS severity, the levels of serum IGF-1 were gradually decreased (F=37.732,P<0.01). There was no significant difference between mild group and healthy people (P>0.05), while there was significant differences between the remaining groups (P<0.01). ②Serum IGF-1 level has no correlation with BMI and age in OSAHS patients(P>0.05), and negatively correlated with LSaO2,and positively correlated with AHI (P<0.01). ③Serum IGF-1 levelï¼»(46.56±3.74)µg/Lï¼½ increased slightly compared with those before treatmentï¼»(42.79±4.87）µg/Lï¼½ in 30 severe patients after treatment with 3 months CPAP and regimen (P<0.01). Serum IGF-1 levelï¼»(56.61±5.46)µg/Lï¼½ increased significantly after treatment for six months; AHI level (18.72±7.36) was significantly lower than that before treatment (48.77±10.51), and LSaO2ï¼»(87.42±8.61)%ï¼½ increased significantly than that before treatmentï¼»(68.33±10.24)%ï¼½.Conclusion:OSAHS patients with decreased serum IGF-1 level may be associated with concurrent insulin resistance. Surgery combined with more than half a year of CPAP treatment can significantly reduce AHI, improve the level of LSaO2 and serum IGF-1. Serum IGF-1 levels could be used as a monitor of efficacy evaluation.

Structural Signature of Plasticity Unveiled by Nano-Scale Viscoelastic Contact in a Metallic Glass.

Room-temperature plasticity in metallic glasses (MGs) is commonly associated with local structural heterogeneity; however, direct observation of the subtle structural change caused by plasticity is vitally important but the data are extremely scarce. Based on dynamic atomic force microscopy (DAFM), here we show that plasticity-induced structural evolution in a Zr-Ni MG can be revealed via nano-scale viscoelastic contacts between an AFM tip and plastically deformed MG surface layers. Our experimental results clearly show a spatial amplification of the nano-scale structural heterogeneity caused by the distributed plastic flow, which can be linked to the limited growth, reorientation and agglomeration of some nano-scale energy-absorbing regions, which are reminiscent of the behavior of the defect-like regions with non-affine deformation as conceived in many theories and models. Furthermore, we are able to experimentally extract the thermodynamic properties of these nano-scale regions, which possess an energy barrier of 0.3-0.5 eV, about half of that for a typical shear transformation event that usually occurs at the onset of plasticity. The outcome of our current work sheds quantitative insights into the correlation between plasticity and structural heterogeneity in MGs.

Manuifolins D, E, and F: new isoflavonoids from Maackia tenuifolia.

Chemical examination of roots of Maackia tenuifolia yielded three new isoflavans, manuifolins D, E, and F, along with the known (6aR, 12aR)-pterocarpin and (6aR,12aR)-maackiain. The new compounds were established as (3R)-5'-(1,1-dimethyl-2-propenyl)-4'- O-(3-methyl-2-butenyl)- 7,2'-dihydroxyisoflavan (1), (3R)-6,5'-bis(1,1-dimethyl-2-propenyl)-7,2',4', -trihydroxyisoflavan (2), and (3R)-5'-(1-isopropylethenyl)-8-(3-methyl-2-butenyl)-7,2',4'- trihydroxyisoflavan (3), respectively, by spectroscopic methods.

[The isolation and identification of four new 2, 2-dimethylchromenes].

Four new 2, 2-dimethylchromenes named leptol B (I), ethylleptol B (II), methylleptol B (III), leptene B (IV), along with a known chromene-methylevodionol (V) have been isolated from the aerial parts of Evodia lepta. Their structures were elucidated by spectroscopic analysis and chemical techniques.