BackgroundBase editors are a class of genome editing tools with the ability to efficiently induce point mutations in genomic DNA, without inducing double-strand breaks or relying on homology-direct repair as in other such technologies. Recently, adenine base editors (ABEs) have been developed to mediate the conversion of A•T to G•C in genomic DNA of human cells, mice, and plants. Here, we investigated the activity and efficiency of several adenine base editors in zebrafish and showed that base editing can be used to create new models of pathogenic diseases caused by point mutations.ResultsThe original ABE7.10 exhibits almost no activity in zebrafish. After codon optimization, we found that a zABE7.10 variant could induce targeted conversion of adenine to guanine in zebrafish at multiple tested genomic loci, and all the target sites showed a high rate of germline targeting efficiency. Furthermore, using this system, we established a zebrafish model of 5q-Syndrome that contained a new point mutation in rps14. The further modification of zABE7.10 by a bipartite nuclear localization signals (bpNLS) resulted in 1.96-fold average improvement in ABE-mediated editing efficiency at four sites.ConclusionsCollectively, this system, designated as zABE7.10, provides a strategy to perform A•T to G•C base editing in zebrafish and enhances its capacity to model human diseases.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0609-1) contains supplementary material, which is available to authorized users.

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IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.

IntroductionOnline health information seeking has been verified to play a crucial role in improving public health and has received close scholarly attention. However, the seeking behavior of older adults, especially the underlying mechanism through which they are motivated to seek health information online, remains unclear. This study addresses the issue by proposing a theoretical model leveraging social cognitive theory.MethodsIT self-efficacy and IT innovativeness were identified as personal factors and professional support and social support were identified as environmental factors. We conducted a survey that included 347 older people in China and examined the research hypotheses with a structural equation model.ResultsIT self-efficacy and IT innovativeness facilitate older adults to seek health information online by increasing their perceived benefit of using the internet. Additionally, professional support and social support enhanced older adults' online seeking behavior by promoting their health awareness. We also found that perceived benefit displayed a stronger impact than health awareness on older adults' behavior related to searching for health information online.ConclusionThis study reveals that IT self-efficacy, IT innovativeness, professional support, and social support will promote older adults to seek health information online by enhancing their health awareness and perceived benefit. The findings of this study provide significant theoretical and practical implications.

Introduction: Mycophenolate mofetil (MMF), a new type of immunosuppressant, has emerged as a frontline agent for treating autoimmune diseases. Mycophenolic acid (MPA) is an active metabolite of MMF. MPA exposure varies greatly among individuals, which may lead to adverse drug reactions such as gastrointestinal side effects, infection, and leukopenia. Genetic factors play an important role in the variation of MPA levels and its side effects. Although many published studies have focused on MMF use in patients after organ transplant, studies that examine the use of MMF in patients with autoimmune diseases are still lacking. Methods: This study will not only explore the genetic factors affecting MPA levels and adverse reactions but also investigate the relationships between UGT1A9 −118(dT)9/10, UGT1A9 -1818T>C, UGT2B7 802C>T, SLCO1B1 521T>C, SLCO1B3 334T>G, IMPDH1 −106G>A and MPA trough concentration (MPA C 0 ), along with adverse reactions among Chinese patients with autoimmune diseases. A total of 120 patients with autoimmune diseases were recruited. The MPA trough concentration was detected using the enzyme multiplied immunoassay technique (EMIT). Genotyping was performed using a real-time polymerase chain reaction (PCR) system and validated allelic discrimination assays. Clinical data were collected for the determination of side effects. Results: SLCO1B1 521T>C demonstrated a significant association with MPA C 0 /d (p=0.003), in which patients with the CC type showed a higher MPA C 0 /d than patients with the TT type (p=0.001) or the CT type (p=0.000). No significant differences were found in MPA C 0 /d among the other SNPs. IMPDH1 −106G>A was found to be significantly related to infections (p=0.006). Subgroup analysis revealed that UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection (p=0.036), while SLCO1B1 521T>C was associated with anemia (p=0.029). Conclusion:For Chinese autoimmune disease patients, SLCO1B1 521T>C was correlated with MPA C 0 /d and anemia. IMPDH1 −106G>A was significantly related to infections. UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection.