Comprehensive information management system for a medical research cohort biobank based on quality by design.

BACKGROUND: With the development of big health and big data, cohort research has become a medical research hotspot. As an important repository of human genetic resources, biobanks must adapt to the requirements of large-scale and efficient operation. Thus, biobanks urgently need to design and build a legal, convenient, and efficient information management system. METHODS: This study applies the concept of "quality by design" to build a comprehensive biobank information management system based on the analysis of user requirements, legal and regulatory risks, and industry-standard requirements. The system integrates the management of scientific research projects, biological specimens, clinical information, quality control, and multi-dimensional information query and development. After 10 months of its operation, the comprehensive management system was evaluated through statistical analysis of the efficiency of the construction of the pregnancy-birth cohort and the quality of genetic resources. RESULTS: Since the system's launch, the statistics on cohort construction efficiency show that the enrollment rate of eligible pregnant women has increased, and the rate of missing volunteers has dropped. The time needed to establish a 1000-person cohort (with complete biological samples and clinical information in early, middle, and late pregnancy) was reduced, and the effective tracking rate of the samples was 77.42%. The error rate of the deep cryogenic refrigerator decreased, with a clinical information integrity rate of 96.47%. CONCLUSIONS: The comprehensive biobank information management system constructed with the "quality by design" concept is well suited to meet the requirements of medical research. This study provides a solution for designing a comprehensive information system for medical institutions' biobanks.

Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells.

Low acrosin activity (LAA) is associated with sperm function anomaly and poor outcomes of in vitro fertilization. In this study, we confirm that 993 semen samples with LAA had a reduced sperm motility and low in vitro fertilization rate in comparison with 1332 normal controls (NC). Proteomic comparison between 11 LAA and 11 NC sperm samples identified 35 upregulated and 99 downregulated proteins in the LAA group. Indeed, proteomic data showed that acrosome enzymes Spam1 and Acrosin were among the downregulated proteins in the LAA group, which was validated by quantitative PCR and immunefluorescent staining of sperm cells. The KEEG pathway analysis revealed a deficiency of GSH and Gln biosynthesis in LAA sperm cells. Immunofluorescent staining of sperms and quantitative PCR verified downregulation of GLUL and GCLC, the key enzymes for GSH and Gln biosynthesis. Moreover, the results of ELISA assay confirmed low levels of GSH and Gln in LAA sperm cells. Mechanistic studies showed that addition of 10 mM H2O2 to semen samples led to a significant reduction of acrosin activity and sperm motility, most possibly by triggering premature acrosome release. In contrast, the presence of 20 mM GSH blocked the oxidative effects of H2O2. Since GSH counteracts the oxidative stress and Gln participates in TCA cycling, their deficiency may affect the redox balance as well as energy production of sperm cells. These findings shed new light on the pathological mechanisms of infertility associated with LAA. Male infertility patients could benefit from GSH supplement by improvement of acrosin activity and other sperm functions.

Allopatric integrations selectively change host transcriptomes, leading to varied expression efficiencies of exotic genes in Myxococcus xanthus.

BACKGROUND: Exotic genes, especially clustered multiple-genes for a complex pathway, are normally integrated into chromosome for heterologous expression. The influences of insertion sites on heterologous expression and allotropic expressions of exotic genes on host remain mostly unclear. RESULTS: We compared the integration and expression efficiencies of single and multiple exotic genes that were inserted into Myxococcus xanthus genome by transposition and attB-site-directed recombination. While the site-directed integration had a rather stable chloramphenicol acetyl transferase (CAT) activity, the transposition produced varied CAT enzyme activities. We attempted to integrate the 56-kb gene cluster for the biosynthesis of antitumor polyketides epothilones into M. xanthus genome by site-direction but failed, which was determined to be due to the insertion size limitation at the attB site. The transposition technique produced many recombinants with varied production capabilities of epothilones, which, however, were not paralleled to the transcriptional characteristics of the local sites where the genes were integrated. Comparative transcriptomics analysis demonstrated that the allopatric integrations caused selective changes of host transcriptomes, leading to varied expressions of epothilone genes in different mutants. CONCLUSIONS: With the increase of insertion fragment size, transposition is a more practicable integration method for the expression of exotic genes. Allopatric integrations selectively change host transcriptomes, which lead to varied expression efficiencies of exotic genes.