The aldehyde dehydrogenase 2 rs671 variant enhances amyloid ß pathology.

In the ALDH2 rs671 variant, a guanine changes to an adenine, resulting in a dramatic decrease in the catalytic activity of the enzyme. Population-based data are contradictory about whether this variant increases the risk of Alzheimer's disease. In East Asian populations, the prevalence of the ALDH2 rs671 variant is 30-50%, making the National Human Brain Bank for Development and Function (the largest brain bank in East Asia) an important resource to explore the link between the ALDH2 rs671 polymorphism and Alzheimer's disease pathology. Here, using 469 postmortem brains, we find that while the ALDH2 rs671 variant is associated with increased plaque deposits and a higher Aß40/42 ratio, it is not an independent risk factor for Alzheimer's disease. Mechanistically, we show that lower ALDH2 activity leads to 4-HNE accumulation in the brain. The (R)-4-HNE enantiomer adducts to residue Lys53 of C99, favoring Aß40 generation in the Golgi apparatus. Decreased ALDH2 activity also lowers inflammatory factor secretion, as well as amyloid ß phagocytosis and spread in brains of patients with Alzheimer's disease. We thus define the relationship between the ALDH2 rs671 polymorphism and amyloid ß pathology, and find that ALDH2 rs671 is a key regulator of Aß40 or Aß42 generation.

Non-covalent interaction of soy protein isolate and catechin: Mechanism and effects on protein conformation.

Understanding the molecular mechanism behind protein-polyphenol interactions is critical for the application of protein-polyphenol compounds in foods. The purpose of this research was to investigate the non-covalent interaction mechanism between soy protein isolate (SPI) and catechin and its effect on protein conformation. We observed that particle size, ζ-potential, and polyphenol bound equivalents of SPI increased significantly after non-covalent modification with catechin. These changes caused SPI to aggregate and form a network-like structure. Fourier transform infrared spectroscopy (FTIR) indicated that increased catechin concentrations caused SPI to become looser and more disordered as its α-helix and ß-sheet transformed into ß-turn and random coil. Furthermore, internal structure of SPI was opened and its hydrophobic groups were exposed to a polar environment, which was demonstrated by decreased surface hydrophobicity. Thermodynamic analysis and molecular docking results showed that the main forces present between SPI and catechin were hydrophobic interactions and hydrogen bonds.

Serum neurofilament light chain in adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disease: Correlation with relapses and seizures.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty-nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat-sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single-molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: ß = 2.02, p = 0.003), seizures (multivariate: ß = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: ß = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.

Generation of a homozygous ALX1 knockout human embryonic stem cell line (WAe001-A-060) by a CRISPR/Cas9 system.

Human ALX1 gene (ALX Homeobox 1) is a protein coding gene and gene ontology annotations related to this gene include DNA-binding transcription factor activity and protein heterdimerization activity. It is necessary for survival of forebrain mesenchyme and may be involved in development of cervix. However, the function of the gene has yet to be determined in humans. Here we generated an ALX1 homozygous human embryonic stem cell line (WAe001-A-060) by a CRISPR/Cas9 system. The WAe001-A-060 has a normal undifferentiated morphology and karyotype, pluripotency and three germ layers differentiation potential in vivo.

The Layered Encapsulation of Vitamin B2 and ß-Carotene in Multilayer Alginate/Chitosan Gel Microspheres: Improving the Bioaccessibility of Vitamin B2 and ß-Carotene.

This research underlines the potential of alginate multilayered gel microspheres for the layered encapsulation and the simultaneous delivery of vitamin B2 (VB) and ß-carotene (BC). Chitosan was used to improve the stability and controlled release ability of alginate-based gel microspheres. It was shown that a clear multilayered structure possessed the characteristics of pH response, and excellent thermal stability. The sodium alginate concentration and the number of layers had notable effects on mechanical properties and particle size of gel microspheres. Fourier-transform infrared spectroscopy and X-ray diffraction analyses further proved that VB and BC were encapsulated within the gel microspheres. Compared with the three-layer VB-loaded gel microspheres, the total release of VB from the three-layer VB and BC-loaded gel decreased from 93.23% to 85.58%. The total release of BC from the three-layer VB and BC-loaded gel increased from 66.11% to 69.24% compared with three-layer BC-loaded gel. The simultaneous encapsulation of VB and BC in multilayered gel microspheres can markedly improve their bioaccessibility and bioavailability. These results showed the multilayer gel microspheres synthesized herein have potential for applications in the layered encapsulation and simultaneous delivery of various bioactive substances to the intestinal tract.