Precise genetic mutation of model animals is highly valuable for functional investigation of human mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology-directed repair (HDR) is usually used for precise genetic mutation, being limited by the relatively low efficiency compared with that of non-homologous end joining (NHEJ). Although inhibition of NHEJ was shown to enhance HDR-derived mutation, in this work, without inhibition of NHEJ, we first generated gene-modified pigs harboring precise orthologous human mutation (Sox10 c.A325>T) via CRISPR/Cas9-induced HDR in zygotes using single-strand oligo DNA (ssODN) as template with an efficiency as high as 80%, indicating that pig zygotes exhibited high activities of HDR relative to NHEJ and were highly amendable to genetic mutation via CIRSPR/Cas9-induced HDR. Besides, we found a higher concentration of ssODN remarkably reduced HDR-derived mutation in pig zygotes, suggesting a possible balance for optimal HDR-derived mutation in zygotes between the excessive accessibility to HDR templates and the activities of HDR relative to NHEJ which appeared to be negatively correlated to ssODN concentration. In addition, the HDR-derived mutation, as well as those from NHEJ, extensively integrated into various tissues including gonad of founder pig without detected off-targeting, suggesting CRISPR/Cas9-induced HDR in zygotes is a reliable approach for precise genetic mutation in pigs.

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Publications by Chinese researchers in scientific journals have dramatically increased over the past decade; however, academic misconduct also becomes more prevalent in the country. The aim of this prospective study was to understand the perceptions of Chinese biomedical researchers towards academic misconduct and the trend from 2010 to 2015. A questionnaire comprising 10 questions was designed and then validated by ten biomedical researchers in China. In the years 2010 and 2015, respectively, the questionnaire was sent as a survey to biomedical researchers at teaching hospitals, universities, and medical institutes in mainland China. Data were analyzed by the Chi squared test, one-way analysis of variance with the Tukey post hoc test, or Spearman's rank correlation method, where appropriate. The overall response rates in 2010 and 2015 were 4.5% (446/9986) and 5.5% (832/15,127), respectively. Data from 15 participants in 2010 were invalid, and analysis was thus performed for 1263 participants. Among the participants, 54.7% thought that academic misconduct was serious-to-extremely serious, and 71.2% believed that the Chinese authorities paid no or little attention to the academic misconduct. Moreover, 70.2 and 65.2% of participants considered that the punishment for academic misconduct at the authority and institution levels, respectively, was not appropriate or severe enough. Inappropriate authorship and plagiarism were the most common forms of academic misconduct. The most important factor underlying academic misconduct was the academic assessment system, as judged by 50.7% of the participants. Participants estimated that 40.1% (39.8 ± 23.5% in 2010; 40.2 ± 24.5% in 2015) of published scientific articles were associated with some form of academic misconduct. Their perceptions towards academic misconduct had not significantly changed over the 5 years. Reform of the academic assessment system should be the fundamental approach to tackling this problem in China.

The fluorescent chelator (FC-1) was designed by combining a metal-chelating unit and a ThT-based Aβ aggregate-binding fluorescent unit. FC-1 is a cell membrane-penetrable chelator with a moderate chelation ability to Cu(2+) and Zn(2+) and can target metal-Aβ40 aggregates. Treatment with FC-1 led to enhanced cytotoxicity of the aggregates, because the aggregates were converted into a pool of oligomers.

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BackgroundRecently, a diverse group of viruses with circular, replication initiator protein(Rep) encoding, single stranded DNA (CRESS-DNA) genomes, were discovered from wide range of eukaryotic organisms ranging from mammals to fungi. Gemycircularvirus belongs to a distinct group of CRESS-DNA genomes and is classified under the genus name of Gemycircularvirus.FindingsHere, a novel gemycircularvirus named GeTz1 from cerebrospinal fluid sample of a child with unexplainable encephalitis was characterized. The novel gemycircularvirus encodes two major proteins, including a capsid protein (Cap) and a replication-associated protein (Rep). Phylogenetic analysis based on the amino acid sequence of Rep indicated that GeTz1 clusters with one gemycircularvirus discovered from bird (KF371633), sharing 46.6 % amino acid sequence identity with each other.ConclusionA novel gemycircularvirus was discovered from cerebrospinal fluid sample of a child with unexplainable encephalitis. Further studies, such as testing human sera for specific antibodies, should be performed to investigate whether gemycircularvirus infects human and is associated with encephalitis.

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