Background
Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common types of neurodegenerative dementia among the elderly with similar symptoms of cognitive decline and ...overlapping neuropsychological profiles. Biological markers to distinguish patients with VaD from AD would be very useful. We aimed to investigate the expression of blood-brain barrier (BBB)-related blood-borne factors of soluble low-density lipoprotein receptor-related protein 1 (sLRP1), cyclophilin A (CyPA), and matrix metalloproteinase 9 (MMP9) and its correlation with cognitive function between patients with AD and VaD.
Materials and methods
Plasma levels of sLRP1, CyPA, and MMP9 were analyzed in 26 patients with AD, 27 patients with VaD, and 27 normal controls (NCs). Spearman’s rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and imaging references. Receiver operating characteristic (ROC) curve analysis was used to discriminate the diagnosis of AD and VaD.
Results
Among these BBB-related factors, plasma CyPA levels in the VaD group were significantly higher than that in the AD group (
p
< 0.05). Plasma sLRP1 levels presented an increasing trend in VaD while maintaining slightly low levels in patients with AD (
p
> 0.05). Plasma MMP9 in different diagnostic groups displayed the following trend: VaD group > AD group > NC group, but the difference was not statistically significant (
p
> 0.05). Furthermore, plasma sLRP1 levels were positively related to MoCA scores, and plasma CyPA levels were significantly correlated with MTA scores (
p
< 0.05) in the AD group. Plasma MMP9 levels were negatively correlated with MoCA scores (
p
< 0.05) in the VaD groups. No significant correlation was detected between the other factors and different cognitive scores (
p
> 0.05). ROC analysis showed a good preference of plasma CyPA AUC = 0.725, 95% CI (0.586–0.865);
p
= 0.0064 in diagnosis.
Conclusion
The plasma CyPA level is a reference index when distinguishing between an AD and subcortical ischemic vascular dementia (SIVD) diagnosis. Blood-derived factors associated with the BBB may provide new insights into the differential diagnosis of neurodegenerative dementia and warrant further investigation.
•A theoretical study on vibration analysis of pipes with FSI is presented.•Pipelines with high fluid pressure and velocity can be solved by developed method.•Several pipeline schemes are discussed to ...illustrate the application of the method.•The proposed method is easier to apply compared to most existing procedures.•Influence laws of structural and fluid parameters on FSI of pipe are analyzed.
Considering the effects of pipe wall thickness, fluid pressure and velocity, a developed 14-equation model is presented, which describes the fluid–structure interaction behavior of pipelines. The transfer matrix method has been used for numerical modeling of both hydraulic and structural equations. Based on these models and algorithms, several pipeline schemes are presented to illustrate the application of the proposed method. Furthermore, the influence laws of supports, structural properties and fluid parameters on the dynamic response and natural frequencies of pipeline are analyzed, which shows using the optimal supports and structural properties is beneficial to reduce vibration of pipelines.
BACKGROUND Macrophages are highly heterogeneous and plastic cells that are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes. ...However, the role of macrophage polarization and the molecular mechanism in modulating atherosclerotic plaque stability remain incompletely understood. Our study investigated the role of STAT6 in regulating macrophage phenotypes to affect atherosclerotic plaque stability. MATERIAL AND METHODS A murine atherosclerosis model with vulnerable plaques was induced with high-cholesterol diet and PCCP surgeries in ApoE-/- mice. Murine macrophages RAW264.7 treated with ox-LDL or IL-4 were used to simulate the in vitro process. pcDNA3.1(-)/STAT6-expressing vectors were transfected into RAW264.7 to evaluate its effect on cell polarization and the involved molecules. RESULTS Unstable plaques presented significantly increased M1 markers (CD86 and iNOS) and less M2 markers (Arg-1 and TGF-β) than the stable plaques. Moreover, we found that STAT6 and p-STAT6 were greatly decreased in the vulnerable plaques and ox-LDL-induced macrophages, while their expression was elevated after IL-4 stimulation. The overexpression of STAT6 substantially reversed the ox-LDL-stimulated macrophage apoptosis and lipid accumulation. STAT6 upregulation promoted the differentiation of macrophage to M2 subtype as reflected by the increased expression of Arg-1 and TGF-β. Furthermore, we found that STAT6 overexpression activated the Wnt-β-catenin signaling by enhancing the translocation of β-catenin, while β-catenin suppression inhibited STAT6 overexpression-induced M2 polarization. CONCLUSIONS STAT6 facilitated atherosclerotic plaque stabilization by promoting the polarization of macrophages to M2 subtype and antagonizing ox-LDL-induced cell apoptosis and lipid deposition in a Wnt-β-catenin-dependent manner.
Plants use a dual defense system to cope with microbial pathogens. The first involves pathogen-associated molecular pattern-triggered immunity which is conferred by membrane receptors, and the second ...involves effector-triggered immunity (ETI), which is conferred by disease-resistance proteins (nucleotide-binding leucine-rich repeat-containing proteins; NLRs). Calmodulin-Binding Protein 60 (CBP60) family transcription factors are crucial for pathogen defense: CBP60g and Systemic Acquired Resistance Deficient 1 (SARD1) positively regulate immunity, whereas CBP60a negatively regulates immunity. The roles of other Arabidopsis (Arabidopsis thaliana) CBP60s remain unclear. We report that CBP60b positively regulates immunity and is redundant with-yet distinct from-CBP60g and SARD1. By combining chromatin immunoprecipitation-PCRs and luciferase reporter assays, we demonstrate that CBP60b is a transcriptional activator of immunity genes. Surprisingly, CBP60b loss-of-function results in autoimmunity, exhibiting a phenotype similar to that of CBP60b gain-of-function. Mutations at the ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-dependent ETI pathway fully suppressed the defects of CBP60b loss-of-function but not those of CBP60b gain-of-function, suggesting that CBP60b is monitored by NLRs. Functional loss of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1, an R-gene, partially rescued the phenotype of cbp60b, further supporting that CBP60b is a protein targeted by pathogen effectors, that is, a guardee. Unlike CBP60g and SARD1, CBP60b is constitutively and highly expressed in unchallenged plants. Transcriptional and genetic studies further suggest that CBP60b plays a role redundant with CBP60g and SARD1 in pathogen-induced defense, whereas CBP60b has a distinct role in basal defense, partially via direct regulation of CBP60g and SARD1.
The absorbing transfer matrix method (ATMM) is applied to dynamics calculation and optimization design of planar branch piping systems combined with the response surface model or method (RSM) and a ...new proposed hybrid RSM (HRSM). A main path is chosen to absorb the influences of sub-branches, and the branch point transfer matrix in the main transfer path is established and proved by the ANSYS simulation and experimental results. It shows that the errors between the ATMM and the finite element method are less than 0.36% in the calculation of the natural frequencies of the two-branch piping system, and the ATMM also agrees well with the dynamics response experimental results of the cross-branch piping system. Then, based on the initial design model of a double-branch piping system, first order natural frequency analysis samples are selected for the branch point positions optimization using the uniform design method (UD) and calculated by the ATMM; the minimum value of the RSM, obtained by fitting the samples with a second-order polynomial (SOP) function, is solved as the best design scheme using the genetic algorithm (GA). Finally, for the problem of supporting positions optimization of a T-branch piping system, a HRSM using the SOP function to fit the variation law with different supporting positions in the samples of the dynamics response optimization target, which is the total x-directional vibration acceleration level (TAC) of three supporting points in the frequency 1–300 Hz and the Fourier basis function to fit the relationship of SOP function error with independent variables is proposed combining the Minimize Prediction (MP) adding point criterion to gradually update the samples, until the HRSM reaches stability and obtains the wanted design solution.
•Proso millet starch nanoparticles were prepared by enzymolysis and recrystallization.•The size of the starch nanoparticles was between 20nm and 100nm.•The crystal pattern changed from A-type (native ...starch) to B-type (nanoparticles).•The sample retrogradated for 12h had the highest degree of crystallinity (47.04%).•It is a rapid way to obtain high yield (about 55%) starch nanoparticles.
Starch nanoparticles were prepared from proso millet starch using a green and facile method combined with enzymolysis and recrystallization. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC) and thermal gravimetric analysis (TGA) were used to characterize the morphology and crystal structure of the starch nanoparticles prepared with different retrogradation time (0.5, 4, 12, and 24h). The results showed that the sizes of the starch nanoparticles were between 20nm and 100nm. The crystal pattern changed from A-type (native starch) to B-type (nanoparticles), and the relative crystallinity of the nanoparticles increased obviously, as compared with the native starch. The nanoparticles prepared with the 12h retrogradation time had the highest degree of crystallinity (47.04%). Compared to conventional acid hydrolysis to make starch nanoparticles, the present approach has the advantage of being quite rapid and presenting a higher yield (about 55%).
The challenge of effectively delivering therapeutic agents to the brain has created an entire field of active research devoted to overcoming the blood brain barrier (BBB) and efficiently delivering ...drugs to the brain. Angiopep-2 can trigger transcytosis and traverse the BBB by recognizing low-density lipoprotein related protein-1 (LRP-1) expressed on the brain capillary endothelial cells. Here, we designed a novel strategy for the delivery of drugs to the brain. The novel drug delivery system was a combination of a receptor-targeting ligand, such as low-density lipoprotein related protein 1, and a cell-penetrating peptide (CPP). It was hypothesized that this conjugate will enhance the delivery of associated therapeutic cargo across the BBB and increase the permeability of a solid tumor. Our findings indicate that the combination of these two agents in a delivery vehicle significantly improved translocation of small molecules (paclitaxel) into the brain compared to the vehicle treatment, which contained only receptor-targeting ligand. The application of this strategy could potentially expand the horizons for the treatment of central nervous system disorders.
Owing to the need for beauty in modern society, cosmetics are essential to enhance femininity and attractiveness. Lipstick is effective in reinforcing femininity and increasing beauty. This study ...conducted a psychophysical experiment to investigate the association between lipstick colors and the impressions they create. Thirty‐five observers were invited to participate in the experiment. They were asked to assess 20 lipstick colors on 23 impression scales. The results showed that the impressions created by the lipstick colors comprised three factors: charm, cuteness, and contemporary. Charm was correlated with a* and lightness value of lipstick color and the color difference between lipstick‐skin colors. Cuteness was negatively correlated with the hue angle of the lipstick colors and lightness differences between lipstick‐skin colors. Contemporary was correlated with chroma differences and negatively correlated with b* of lipstick color. These lipstick colors can be classified into three groups based on impression factors. The results showed that a* value of lipstick color and the color difference (△E) between lipstick and skin color are identified to determine the grouping of lipstick colors.
Lipstick colors are placed in impression space and classification.
Objective: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. Methods: Pueraria lobata‘s potential targets and ...signaling pathways in treating alcohol‐induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol‐induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT‐qPCR, western blot analysis, and immunohistochemistry. Results: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol‐induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. Conclusion: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol‐induced iron overload by inhibiting the MAPK/ERK signaling pathway.
The development, survival, and fecundity data of Conogethes punctiferalis (Guenée) (Lepidoptera: Crambidae) reared on chestnut (Castanea mollissima Blume), maize (Zea mays L.), sunflower (Helianthus ...annuus L.), hawthorn (Crataegus pinnatifida Bunge), and apple (Malus domestica Miller) were collected at 25 ± 1°C and 70 ± 5% RH. Raw data were analyzed and compared by using the age-stage, two-sex life table. The mean fecundity (F) was the highest (282.3 eggs per female) when larvae were reared on chestnut. The lowest mean fecundity (19.2 eggs per female) occurred on apple. The net reproductive rates (R0) were 134.52, 106.77, 30.29, 27.61, and 8.63 offspring on chestnut, maize, sunflower, hawthorn, and apple, respectively. The intrinsic rates of increase (r) were 0.1359, 0.1326, 0.0807, 0.0811, and 0.0448 d-1 on chestnut, maize, sunflower, hawthorn, and apple, respectively. Computer projections based on the age-stage, two-sex life table revealed the stage structure and variability of the population growth of C. punctiferalis. Our results demonstrated that although chestnut and maize were the most suitable host plants for C. punctiferalis, the moths were also able to develop and reproduce on sunflower, hawthorn, and apple.