Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD patients.However,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain unclear.Methods:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice.Changes in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were examined.In addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice.Results:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive impairments.These mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal cortex.Furthermore,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis.Abnormal expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also observed.Conclusion:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice.The mechanism may involve the induction of central and peripheral lipid metabolism disorders.Therefore,modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression.This study also provided a better animal model for studying AD comorbid with depression.

Deoxygenation of methyl laurate to hydrocarbons on silica-supported Ni-Mo phosphides: Effect of calcination temperatures of precursor

SiO2-supported Ni-Mo bimetallic phosphides were prepared by temperature-programmed reduction （TPR） method from the phosphate precur- sors calcined at different temperatures. Their properties were characterized by means of ultraviolet-visible diffuse reflectance spectroscopy （UV-Vis DRS）, H2 temperature-programmed reduction （H2-TPR）, X-ray diffraction （XRD）, transmission electron microscopy （TEM）, CO chemisorption, H2 and NH3 temperature-programmed desorptions （H2-TPD and NH3-TPD）. Their catalytic performances for the deoxygena- tion of methyl laurate were tested in a fixed-bed reactor. When the precursors were calcined at 400 and 500 ℃, respectively, NiMoP2 phase could be formed apart from Ni2P and MoP phases in the prepared C400 and C500 catalysts. However, when the precursors were calcined at 600, 700 and 800 ℃, respectively, only Ni2P and MoP phases could be detected in the prepared C600, C700 and C800 catalysts. Also, in C400, C500 and C600 catalysts, Mo atoms were found to be entered in the lattice of Ni2P phase, but the entering extent became less with the increase of calcination temperature. As the calcination temperature of the precursor increased, the interaction between Ni and Mo in the prepared catalysts decreased, and the phosphide crystallite size tended to increase, subsequently leading to the decrease in the surface metal site density and the acid amount. C600 catalyst showed the highest activity among the tested ones for the deoxygenation of methyl laurate. As the calcination temperature of the precursor increased, the selectivity to C12 hydrocarbons decreased while the selectivity to C11 hydrocarbons tended to increase. This can be mainly attributed to the decreased Ni-Mo interaction and the increased phosphide particle size. In sum, the structure and performance of Ni-Mo bimetallic phosphide catalyst can be tuned by the calcination temperature of precursor.

Thioetherification of isoprene and butanethiol on transition metal phosphides

Thioetherification between mercaptan and diolefin is an efficient process to remove mercaptans in FCC gasoline at mild condition, during which the selective hydrogenation of diolefin to monoolefin is also expected. Here, Si O2 supported transition metal（Fe, Co, Ni, Mo and W） phosphides were tested for the thioetherification of isoprene and butanethiol on a fixed-bed reactor at 120℃ and 1.5 MPa H2, and their structure before and after reaction was characterized by means of XRD, HRTEM, N2 sorption, CO chemisorption, NH3-TPD, XPS and TG. It was found that, among different metal phosphides, Mo P/Si O2 showed the best performance, and the optimal nominal Mo P loading was 25%. Apart from the nature of metal, the density of metal and acid sites determined the catalyst performance. Metal site was mainly responsible for hydrogenation of isoprene, while acid site dominantly contributed to the thioetherification and the polymerization of olefins. Moreover, a balance between metallic and acidic functions is required to arrive at a desired performance. Excessive metal sites or acid sites led to the over-hydrogenation of isoprene or the severe polymerization of olefins, respectively. 25%Mo P/Si O2 was tested for 37 h time on stream, and butanethiol conversion maintained at 100%; although isoprene conversion remarkably decreased, the selectivity to isopentenes exceeded 80% after reaction for 11 h. We suggest that the deactivation of Mo P/Si O2 is mainly ascribed to the butanethiol poisoning and the carbonaceous deposit, especially the former.

Study on the Weld-Bonding Process Optimization and Mechanical Performance of Aluminum Alloy Joints

The 5754 aluminum alloy has been widely used in the automotive industry to reduce the weight of vehicles.The weld-bonding(WB)process comprising resistance spot welding and adhesive bonding processes effectively improves the mechanical properties of joints.However,it is still a great challenge in the WB process to obtain high-quality and defect-free nuggets of aluminum alloys.In this study,the parameters of the WB process are optimized and the mechanism of generation of defects during WB is analyzed.The results show that the welding parameters have a significant effect on the nugget sizes,among which the welding current plays the most important role.The residual adhesive can easily cause defects during welding,e.g.,expulsion and porosity in the nugget.This can be effectively avoided by optimizing the welding parameters.In addition,the gas in the joints is effectively reduced by adding an appropriate preheating pulse prior to welding,thus lowering the damage degree of the adhesive layer.As a result,welded joints with better weld nugget quality and more stable mechanical properties are obtained.

Steam reforming of toluene as a tar model compound with modified nickel-based catalyst

Catalytic steam reforming is a promising route for tar conversion to high energy syngas in the process of biomass gasification. However, the catalyst deactivation caused by the deposition of residual carbon is still a major challenge. In this paper, a modified Ni-based Ni-Co/Al2O3-CaO (Ni-Co/AC) catalyst and a conventional Ni/Al2O3 (Ni/A) catalyst were prepared and tested for tar catalytic removal in which toluene was selected as the model component. Experiments were conducted to reveal the influences of the reaction temperature and the ratio between steam to carbon on the toluene conversion and the hydrogen yield. The physicochemical properties of the modified Ni-based catalyst were determined by a series of characterization methods. The results indicated that the Ni-Co alloy was determined over the Ni-Co/AC catalyst. The doping of CaO and the presence of Ni-Co alloy promoted the performance of toluene catalytic dissociation over Ni-Co/AC catalyst compared with that over Ni/A catalyst. After testing in steam for 40 h, the carbon conversion over Ni-Co/AC maintained above 86% and its resistance to carbon deposition was superior to Ni/A catalyst.