Accurate and up-to-date data on the frequency of haemoglobinopathies among the populations of Guangxi Zhuang Autonomous Region, where haemoglobinopathies are most endemic in China, are required. In our study, a total of 5789 samples obtained from members of the Han, Zhang, and Yao ethnic groups in six geographical areas of Guangxi Province were analysed systematically in terms of both haematological and molecular parameters. The results presented that the total heterozygote frequency of thalassaemias and other haemoglobinopathies was 24.51%, of which 17.55% was due to alpha-thalassaemia, 6.43% to beta-thalassaemia, 0.38% to structural haemoglobin variants, and 0.16% to delta-thalassaemia. The mutational spectrum among the local population for each type of disorder was described, including the first report on the true prevalence of three silent alpha thalassemia defects, -alpha(3.7)/(4.78%), -alpha(4.2)/(1.61%) and Hb Westmead (alpha(WS)alpha/) (1.57%) and of delta-thalassemia resulting from five novel and two rare mutations never before identified in Chinese individuals. Comparison of the frequencies of alpha-globin mutations among the ethnic groups showed that there was a statistically significant difference between the Han (15.71%) and Zhuang (20.12%), and between the Han (15.71%) and Yao (20.84%) ethnic groups. In addition, we have performed the first extensive study of haematological parameters of the Hb Westmead mutation using a group of Chinese subjects with compound heterozygosity for this variant and an alpha-thalassaemia deletion. The knowledge gained in this study will enable us to estimate the health burden in this high-risk population and to elucidate the various genetic alterations that underlie haemoglobinopathies.

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.

Background: Schwann cells (SC) which are myelin-forming cells in peripheral nervous system are very useful for the treatment of diseases of peripheral nervous system and central nervous system. However, it is difficult to obtain sufficient large number of SC for clinical use, so alternative cell systems are desired.

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Aim: To investigate the effects of the wingless-related MMTV integration site 3A (Wnt3a) signaling on the proliferation, migration, and the myogenic and adipogenic differentiation of rat bone marrow mesenchymal stem cells (rMSC). Methods: Primary MSC were isolated and cultured from Sprague-Dawley rats and characterized by flow cytometry. Mouse L cells were transfected with Wnt3a cDNA, and conditioned media containing active Wnt3a proteins were prepared. Cell proliferation was evaluated by cell count and 5-bromodeoxyuridine incorporation assay. The migration of rMSC was performed by using a transwell migration and wound healing assay. The myogenic and adipogenic differentiation in rMSC were examined by light microscopy, immunofluorescence, and RT-PCR at different time points after myogenic or adipogenic introduction. Results: Wnt3a signaling induced β-catenin nuclear translocation and activated the Wnt pathway in rMSC. In the presence of Wnt3a, rMSC proliferated more rapidly than the control cells, keeping their differentiation potential. Moreover, Wnt3a signaling induced 2.62% and 3.76% of rMSC-expressed desmin and myosin heavy chain after being cultured in myogenic medium. The myogenic differentiation genes, including Pax7, MyoD, Myf5, Myf4, and myogenin, were activated after Wnt3a treatment. On the other hand, Wnt3a inhibited the adipogenic differentiation in rMSC through the downregulated expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma). Furthermore, Wnt3a promoted the migration capacity of rMSC. Conclusion: The results indicate that Wnt3a signaling can induce myogenic differentiation in rMSC. Wnt3a signaling is also involved in the regulation of the proliferation and migration of rMSC. These results could provide a rational foundation for cell-based tissue repair in humans.

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Five new 20,24-bishomoscalarane sesterterpenes, phyllactones A [1], B [2], C [3], D [4], and E [5], are reported from the sponge Phyllospongia foliascens collected in the waters of the Nansha Islands in the South China Sea. Structural elucidation of these compounds is based on spectral data and chemical conversions. Phyllactones A and B show moderate cytotoxicity against KB cells (IC50 20 micrograms/ml).