Search

The C allele of rs11136000 variant in the clusterin (CLU) gene represents the third strongest known genetic risk factor for late-onset Alzheimer's disease. However, whether this single-nucleotide polymorphism (SNP) is functional and what the underlying mechanisms are remain unclear. In this study, the CLU rs11136000 SNP is identified as a functional variant by a small-scale CRISPR-Cas9 screen. Astrocytes derived from isogenic induced pluripotent stem cells (iPSCs) carrying the "C" or "T" allele of the CLU rs11136000 SNP exhibit different CLU expression levels. TAR DNA-binding protein-43 (TDP-43) preferentially binds to the "C" allele to promote CLU expression and exacerbate inflammation. The interferon response and CXCL10 expression are elevated in cytokine-treated C/C astrocytes, leading to inhibition of oligodendrocyte progenitor cell (OPC) proliferation and myelination. Accordingly, elevated CLU and CXCL10 but reduced myelin basic protein (MBP) expression are detected in human brains of C/C carriers. Our study uncovers a mechanism underlying reduced white matter integrity observed in the CLU rs11136000 risk "C" allele carriers. [Display omitted] • The CLU rs11136000 SNP is identified as a functional variant • C/C astrocytes exhibit elevated CLU expression and inflammatory response • TDP-43 preferentially binds to the "C" allele to promote CLU expression • Cytokine-treated C/C astrocytes inhibit OPC proliferation and myelination Liu et al. show that the CLU rs11136000 is a functional variant by a small-scale CRISPR-Cas9 screen. Astrocytes derived from iPSCs carrying the risk allele "C" exhibit elevated CLU expression and inflammatory response. Cytokine-treated C/C astrocytes inhibit OPC proliferation and myelination through activating the interferon response and inducing CXCL10 expression. [ABSTRACT FROM AUTHOR]

Gum arabic (GA) is the most widely used natural emulsifier in food industry. However, due to its high price and unstable market supply, the search for substitutes of gum arabic has attracted the attention of researchers. Recent studies have shown that sugar beet pectin (SBP) has great potential as a natural emulsifier. However, the mechanisms and differences of GA- and SBP-stabilized emulsions are still unclear. In this study, the interfacial behavior of GA and SBP on the oil-water interface was studied and compared through dissipative quartz crystal microbalance and interfacial dilatational rheology. Then, droplet size, zeta-potential and viscosity of the emulsion stabilized by GA and SBP were measured. Meanwhile, the long-term stability of GA- and SBP-stabilized emulsions was evaluated and compared through a LUMiSizer stability analyzer. The study showed that at the same concentration, SBP-stabilized emulsion had significant advantages of a smaller droplet size, a larger viscosity, a thicker and more elastic interfacial layer, and better long-term stability. A comparison of the long-term stability of SBP2.0%- and GA15.0%-stabilized emulsions, evidenced that the elasticity of the interfacial layer plays a crucial role in the long-term stability of emulsions. This research may provide useful information for finding alternatives to GA. [Display omitted] • SBP and GA forms different interfacial layers at oil-in-water interface. • Elasticity of interfacial layer is crucial to long-term stability of emulsion. • SBP may be a good alternative to GA. [ABSTRACT FROM AUTHOR]

In this study, structural characterization and chemical compositions of three pectins from different sources were studied, which showed that compared with apple pectin (AP) and citrus peel pectin (CPP), sugar beet pectin (SBP) has higher protein contents, feruloylated groups, acetyl groups and more hairy regions. Molecular dynamics simulations showed that HG domain was tiled on the oil-water interface, while RG-Ⅰ and RG-Ⅱ domains were adsorbed on the oil-water interface in a folded form, resulting in a thick viscoelastic film. Dissipative quartz crystal microbalance (QCM-D) and dilatational rheology studies showed that under high-concentration and acidic conditions, pectin molecules were adsorbed in multiple layers at the oil-water interface, forming a thicker viscoelastic film, which was crucial for the long-term stability of pectin-stabilized emulsions. [Display omitted] • HG domain was tiled on the oil-water interface. • RG-Ⅰ and RG-Ⅱ domains adsorbed on the oil-water interface in a folded form. • Pectin molecules adsorbed in multiple layers under acidic conditions. [ABSTRACT FROM AUTHOR]

Pin1, a peptide prolyl cis-trans isomerase, is overexpressed and/or overactivated in many human malignancies. However, whether Pin1 regulates the immunosuppressive TME has not been well defined. In this study, we detected the effect of Pin1 on immune cells and immune checkpoint PD-L1 in the TME of CRC and explored the anti-tumor efficacy of Pin1 inhibitor ATRA combined with PD-1 antibody. We found that Pin1 facilitated the immunosuppressive TME by raising the proportion of myeloid-derived suppressor cells (MDSCs) and declining the percentage of CD8+ T cells and CD4+ T cells. Pin1 restrained PD-L1 protein expression in CRC cells and the effect was tempered by endoplasmic reticulum (ER) stress inducers. Mechanically, Pin1 overexpression decreased the stability of PD-L1 and promoted its degradation by mitigating ER stress. Silencing or inhibiting Pin1 promoted PD-L1 protein expression by inducing ER stress. Hence, Pin1 inhibitor ATRA enhanced the anti-tumor efficacy of PD-1 antibody in the CRC allograft by upregulating PD-L1. Our results reveal the critical and pleiotropic effects of Pin1 on managing the immune cells and immune checkpoint PD-L1 in the TME of CRC, providing a new promising candidate for combination with immunotherapy. [Display omitted] • Pin1 facilitates immunosuppressive TME by managing immune cells in CRC. • Pin1 promotes PD-L1 degradation by mitigating ER stress. • Inhibition of Pin1 enhances the therapeutic efficacy of the PD-1 antibody. [ABSTRACT FROM AUTHOR]

Previous studies have shown that Mesona chinensis Benth polysaccharide (MP) has a variety of physiological activities, including anti-inflammation, anti-oxidation, immune regulation, etc. In addition, MP can also enhance the gel properties of starch. However, there are few reports about the interfacial properties and long-term emulsion stability of MP. In this study, we measured adsorption kinetics of MP molecules on the oil-water interface, interfacial viscoelasticity and adsorption mass, interfacial film thickness, the resistance of the interfacial film to external perturbations, and droplet size, zeta-potential, viscosity and long-term stability of MP-stabilized emulsion under different pH values. The results represented that MP could form much thicker and more elastic interfacial films on the oil-water interface under pH7 and pH9 conditions than that under pH5 condition. Besides, this interfacial film has stronger resistance to external perturbations, which is very significant for the long-term emulsion stability. This study explores the stability mechanism and application of MP in emulsion, which has a positive effect on expanding the application scene and scope of MP. [Display omitted] • Highly elastic interfacial films have greater resistance to external perturbations. • PH influences the stability and rheological behavior of MP-stabilized emulsion. • Elasticity of interfacial layer is crucial to long-term stability of emulsion. • MP-stabilized emulsion at pH7 and pH9 has better stability than that at pH5. [ABSTRACT FROM AUTHOR]