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INTRODUCTION: More robust non‐human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3′ and 5′ intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non‐human primate model. RESULTS: We observed early changes of AD‐related pathological proteins (cerebrospinal fluid Aβ42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1‐ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1‐ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD‐related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD‐associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. Highlights: A dual‐guide CRISPR/Cas9 system successfully mimics AD PSEN1‐ΔE9 mutation by genomic excision of exon 9.PSEN1 mutant cynomolgus monkey‐derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aβ secretion.Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys.Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD‐related pathological proteins (increased Aβ42 and phosphorylated tau). [ABSTRACT FROM AUTHOR]

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self‐assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil‐binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G′ > G″). The results of differential scanning calorimeter and X‐ray diffraction further confirmed that the properties of RSO‐based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Zn(II) can efficiently promote the catalytic performance of imidazolium salt ionic liquids (imi‐ILs) for the chemical fixation of CO2 into epoxides. To obtain sustainability, immobilized bifunctional catalysts containing both imi‐ILs and Zn(II) were prepared using bimodal mesoporous silica (BMMs) as carrier, through grafting of Zn(OAc)2 and 1‐(trimethoxysilyl)propyl‐3‐methylimidazolium chloride (Si‐imi) separately in the nanopores. The catalysts, named as BMMs−Zn&ILs, were identified as efficient catalysts for cycloaddition reaction of CO2 into epoxides under solvent‐free conditions. BMMs−Zn&ILs showed good catalytic activity, which increased with the increase of the molar ratio of Zn(II) to Si‐imi. As a comparison, different catalytic systems including homogeneous imi‐IL, BMMs‐ILs and BMMs−Zn were studied to demonstrate different cooperation behaviors. Furthermore, the kinetics studies of homogeneous and heterogeneous bifunctional catalysts were employed to confirm the differences, as well as to support the proposed cooperative catalysis mechanism in the nanopores. [ABSTRACT FROM AUTHOR]

Cytoskeletal remodeling is indispensable for the development and maintenance of neuronal structures and functions. However, the molecular machinery that controls the balance between actin polymerization and depolymerization during these processes is incompletely understood. Here, we report that coronin 2B, a conserved actin‐binding protein, is concentrated at the tips of developing dendrites and that knockdown of coronin 2B inhibits the growth of dendrites. Importantly, coronin 2B interacts with actin and reduces the F‐actin/G‐actin ratio. Furthermore, the coiled‐coil domain of coronin 2B is required for its oligomerization, thus confining coronin 2B to neurite tips. Our findings collectively suggest that coronin 2B is important for promoting dendrite outgrowth by limiting the speed of actin polymerization at growth cones. [ABSTRACT FROM AUTHOR]

Lonicerae Japonicae Flos (LJF) is a typical herbal medicine and is used as a functional food. LJF, which has complex chemical compounds, has various biological effects. The global metabolomics, focusing on both the endogenous and exogenous metabolites, have not yet been investigated for LJF in normal healthy rats using LC–MS. In this study, plasma metabolomics was analyzed after the administration of LJF at different time intervals, and the exogenous metabolites were identified. Partial least squares discriminant analysis showed significant differences in chemical content in the dosed rats. Cholic acid, indoleacrylic acid, indolelactic acid, hippuric acid, N‐acetyl‐phenylalanine, and N‐acetyl‐serotonin significantly accumulated in the dosed rats. Lysophosphatidylethanolamine and lysophosphatidylcholine content, including plasmalogen, increased. There were 25 components of LJF, including 15 prototypes and 10 metabolites, that were identified. The 15 prototypes included phenolic acids, flavonoids, and iridoids, and their contents decreased with an increase in the administration time. Glucuronidation and sulfation of polyphenols were found for LJF. The exogenous glucuronide and sulfate metabolites—including dihydrocoumaric acid‐sulfate, dihydrocaffeic acid‐sulfate, dihydroferulic acid‐sulfate, apigenin‐glucuronide, apigenin‐glucuronide‐sulfate, isorhamnetin‐glucuronide‐sulfate, and others—were identified with a neutral loss of 176 and 80, respectively. The metabolic differences found in the study may serve as biomarkers of LJF consumption and promote the understanding of the mechanism of action of LJF. [ABSTRACT FROM AUTHOR]

Electrochemical CO2 reduction to value‐added chemicals is a critical and challenging process for research of sustainable energy. Herein, we synthesize new nickel single atom catalysts embedded in nitrogen doped hollow carbon spheres (Ni−N/C‐x) via thermal treatment of Ni salts and nitrogen doped hollow carbon spheres (N/C‐x). The state of Ni species on Ni−N/C‐x can be tuned by the nitrogen species of N/C‐x and pyrrolic‐N favors the formation of atomic Ni species. Two catalysts, namely, Ni−N/C‐1/4 contains more pyrrolic‐N and more amount of atomic Ni species than that on Ni−N/C‐3/2 have been prepared. During all the measurement potential range, Ni−N/C‐1/4 displays a much higher catalytic activity for CO2 reduction to CO than Ni−N/C‐3/2. Within the potential range of −0.63 V to −0.98 V versus reversible hydrogen electrode (RHE), the faradaic efficiencies of CO on Ni−N/C‐1/4 exceed 70 %. Furthermore, Ni−N/C‐1/4 exhibits high selectivity for CO and excellent stability during 4.5 h of CO2 reduction electrolysis at the potential of −0.78 V versus RHE. [ABSTRACT FROM AUTHOR]

Abstract: Electrospun composite membranes in multiscale structures are developed for bone tissue engineering. Aligned polycaprolactone (PCL) fibers entrapping CA‐HAp microparticles (containing CaCO3, hydroxyapatite, and casein in a hierarchical organization) are electrospun to find whether synergistic effects of fiber alignment and CA‐HAp microparticles on improving osteogenic differentiation can be obtained. CA‐HAp microparticles are in a spherical morphology of 1.42 ± 0.26 µm. Their presence increases fiber diameter and does not significantly affect fiber alignment. On all membranes, adipose derived stem cells (ADSCs) from humans spread very well. On a random group, cells distribute randomly and the presence of CA‐HAp microparticles facilitates cell proliferation, especially for the one at CA‐HAp/PCL 50 wt%; the one at CA‐HAp/PCL 20 wt% shows significantly much higher alkaline phosphatase (ALP) activity (112.0% higher) than the pure PCL membrane. On aligned samples, cells align along fibers and expression of ALP is enhanced. However, at the same composition (CA‐HAp/PCL 20 wt%), the random sample has much higher ALP activity than the aligned sample. The expressions of osteogenic marker genes are also evaluated. Combining the results and the applicability of membranes together, the random membrane at CA‐HAp/PCL 20 wt% is the best candidate for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Tobacco smoke (TS) is a major causative agent to lead to chronic bronchitis (CB). However the mechanisms of CB induced by TS are unclear. In this report, rats were exposed to different concentrations of TS and the metabolic features of CB were characterized by using a nontargeted metabolic profiling method based on liquid chromatography-mass spectrometry (LC-MS) to detect the altered metabolic patterns in serum from CB rats and investigate the mechanisms of CB. 11 potential biomarkers were identified in serum of rats. Among them, the levels of lysophosphatidylethanolamine (18:1), lysophosphatidic acid (18:1), lysophosphatidylethanolamine (18:0), lysophosphatidylethanolamine (16:0), lysophosphatidylethanolamine (20:4), docosahexaenoic acid, 5-hydroxyindoleacetic acid and 5′-carboxy- γ-tocopherol were higher in TS group compared to control group. Conversely, the levels of 4-imidazolone-5-propionic acid, 12-hydroxyeicosatetraenoic acid and uridine were lower in TS group. The results indicated that the mechanism of CB was related to amino acid metabolism and lipid metabolism, particularly lipid metabolism. In addition, lysophosphatidylethanolamines were proved to be important mediators, which could be used as biomarkers to diagnose CB. These results also suggested that metabolomics was suitable for diagnosing CB and elucidating the possible metabolic pathways of TS-induced CB. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a leading cause of mortality in the elderly. Genetics studies have identified variants associated with AD. Moreover, Polygenic score analysis can infer the risk of developing AD solely on the basis of genotype information. Method: Whole‐genome sequencing was performed in 2 AD cohorts recruited from mainland China (n = 2,340) and Hong Kong (n = 1,009). Genotype and phenotype data were input into a neural network model that output a polygenic score. Regression analysis was subsequently conducted to examine the associations between the resultant polygenic scores and AD plasma biomarkers. Result: The resultant polygenic scores were associated with AD pathogenesis and the levels of specific AD plasma biomarkers in the Chinese population. Conclusion: The results suggest that deep‐learning methods have utility for investigating the underlying mechanisms of AD and promote the possibility of developing a genotype‐based strategy for AD risk prediction. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a leading cause of mortality in the elderly. Although genome‐wide association studies (GWASs) have identified dozens of genetic risk factors in the Caucasian population, their associations with AD in the Chinese population have not been thoroughly investigated. Method: A TaqMan‐based single‐nucleotide polymorphism genotyping assay was implemented to evaluate Caucasian GWAS risk variants in a Hong Kong Chinese AD cohort (n = 732). Logistic regression analysis was performed to examine the associations between these risk variants and AD, adjusting for age and gender. Result: Several Caucasian AD candidate loci including SORL1(rs11218343) and ABCA7(rs4147929) were associated with AD in the Hong Kong Chinese AD cohort. Conclusion: Known Caucasian AD GWAS candidates can contribute to AD risk in the Chinese population. This suggests that AD pathogenesis might share general mechanisms in both Asian and Caucasian populations. [ABSTRACT FROM AUTHOR]