Blackberry polysaccharides with certain molecular weight distribution have good bioactivity. In this research, type 2 diabetes mice were used to investigate the hypoglycemic effect of blackberry polysaccharides with three different molecular weights, BBP (603.59 kDa), BBP-8 (408.13 kDa) and BBP-24 (247.62 kDa), through gut microbiota modulation. Blackberry polysaccharides exhibited stronger hypoglycemic activity after degradation, and the FBG of BBP, BBP-8 and BBP-24 was reduced to 20.21 ± 4.17 mmol L-1, 20.6 ± 7.23 mmol L-1 and 17.32 ± 6.59 mmol L-1 and OGTT-AUC was reduced by 14.76%, 19.80% and 25.04%, respectively, after 8-week intervention. Furthermore, 16S rRNA gene sequencing analysis indicated that BBP, BBP-8 and BBP-24 could reshape the diversity and composition of the gut microbiota. From 0 to 4 weeks, the F/B of BBP, BBP-8 and BBP-24 reduced by 56.44%, 47.19% and 62.04%, reaching 3.39, 6.54, and 3.11 in the 8th week, respectively, which suggested the faster utilization of BBP-24. Moreover, the intervention the three blackberry polysaccharides increased the relative abundance of the targeted beneficial bacteria Oscillospira and Bacteroidaceae Bacteroides and decreased the relative abundance of the pathogenic bacterium Allobaculum. In general, the result demonstrated that blackberry polysaccharides with a lower molecular weight are more easily fermented, making the theoretical basis for the development of blackberry polysaccharides as a probiotic food to rapidly regulate intestinal flora for type 2 diabetes.
Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.