Hybrid active and passive local shimming (HAPLS) for two-region MRI.

PURPOSE: An MRI scanner is equipped with global shim systems for shimming one region of interest (ROI) only. However, it often fails to reach state-of-the-art when shimming two isolated regions of interest simultaneously, even though the two-area shimming can be essential in scan scenarios, such as bilateral breasts or dyadic brains. To address these challenges, a hybrid active and passive local shimming technique is proposed to simultaneously shim two isolated region-of-interest areas within the whole FOV. METHODS: A local passive shimming system is constructed by optimized bilateral ferromagnetic chip arrays to compensate for the magnet's significant high-order B0 inhomogeneities at the boundary of the manufacturer's specified homogeneous volume, thus locally improving the available FOV. The local active shimming consists of 40-channel DC loops powered by 64-channel current amplifiers. With the optimized current distribution, active shimming can correct the residual low-order B0 inhomogeneities and subject-specific field inhomogeneities. In addition, active shimming is used to homogenize the center frequencies of the two regions. RESULTS: With the implementation of the hybrid active and passive local shimming, the 95% peak-to-peak was reduced from 1.92 to 1.12 ppm by 41.7%, and RMS decreased from 0.473 to 0.255 ppm by 46.1% in a two-phantom experiment. The volume ratio containing MR voxels within a 0.5-ppm frequency span increased from 64.3% to 81.3% by 26.3%. CONCLUSION: The proposed hybrid active and passive local shimming technique uses both passive and active local shimming, and it can efficiently shim two areas simultaneously, which is an unmet need for a commercial MRI scanner.

Comparative iTRAQ Proteomics Reveals Multiple Effects of Selenium Yeast on Dairy Cows in Parturition.

The effects of prepartum dietary supplementation with selenium yeast on low abundant plasma proteins in postpartum dairy cows are not known. In this study, 24 healthy parturient dairy cows were divided into two groups (group C, a control group, and group T, a selenium treatment group). Low abundance proteins were extracted from plasma samples of calving cows, and 542 proteins were identified by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis. Dietary supplementation with selenium yeast caused differential abundance of 48 proteins with a fold change of more than 1.2 or less than 0.83 (p < 0.05); 14 proteins were upregulated and 34 were downregulated. The top five gene ontology (GO) enrichment terms for the differentially expressed proteins were protein homotetramerization (or tetramerization), defense response to bacteria or fungus, acute-phase reactions, nucleotide catabolic process, and positive regulation of lipid metabolic process. All proteins involved in acute-phase reactions were downregulated, indicating that selenium ameliorates systemic inflammation. The vast majority of proteins involved in the defense response to microorganisms were downregulated, thereby affecting innate immunity. The decreased abundance of apolipoprotein A-I and apolipoprotein C-II, critical proteins for positive regulation of lipid metabolism, indicated that selenium may optimize lipid metabolism. The iTRAQ results showed that prenatal supplementation with yeast selenium can relieve systemic inflammation after parturition. Moreover, selenium may reduce the effects of metabolic diseases, which can improve glyconeogenesis and prevent ketosis and fatty liver.

First report of Blastocystis in giant pandas, red pandas, and various bird species in Sichuan province, southwestern China.

Blastocystis is a common enteric protist that colonizes humans and a wide range of animals. Although some studies have reported incidences of Blastocystis in humans and animals in China, there is no information available on the prevalence of Blastocystis in giant pandas, red pandas, or bird species. The aims of the present study were to determine the prevalence, subtype distribution, and genetic characterizations of Blastocystis in these animals in a captive situation in southwestern China, as well as assess the zoonotic potential of Blastocystis isolates. A total of 168 fecal specimens, including 81 from giant pandas, 23 from red pandas, 38 from black swans, 11 from ruddy shelducks, and 15 from green peafowl were collected at the Chengdu Research Base of Giant Panda Breeding in Sichuan province. The overall minimum prevalence of Blastocystis was 11.3% (19/168) based on PCR amplification of the barcode region of the SSU rRNA gene. The highest prevalence of Blastocystis was observed in ruddy shelduck (18.2%) and the lowest was found in green peafowl (6.7%). The prevalence of Blastocystis in giant pandas >5.5 years of age was higher than that in younger giant pandas. Two potentially zoonotic subtypes (ST1 and ST8) were identified, and ST1 (n = 12) was found to be more prevalent than ST8 (n = 7). To the best of our knowledge, this is the first report of the prevalence and subtypes of Blastocystis in giant pandas, red pandas, and bird species in China. The findings of this study will improve our understanding of the genetic diversity and public health potential of Blastocystis.

Genome-wide DNA methylation profile of prepubertal porcine testis.

The biological structure and function of the mammalian testis undergo important developmental changes during prepuberty and DNA methylation is dynamically regulated during testis development. In this study, we generated the first genome-wide DNA methylation profile of prepubertal porcine testis using methyl-DNA immunoprecipitation (MeDIP) combined with high-throughput sequencing (MeDIP-seq). Over 190 million high-quality reads were generated, containing 43642 CpG islands. There was an overall downtrend of methylation during development, which was clear in promoter regions but less so in gene-body regions. We also identified thousands of differentially methylated regions (DMRs) among the three prepubertal time points (1 month, T1; 2 months, T2; 3 months, T3), the majority of which showed decreasing methylation levels over time. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that many genes in the DMRs were linked with cell proliferation and some important pathways in porcine testis development. Our data suggest that DNA methylation plays an important role in prepubertal development of porcine testis, with an obvious downtrend of methylation levels from T1 to T3. Overall, our study provides a foundation for future studies and gives new insights into mammalian testis development.

Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells.

Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6th coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

Dopamine receptor 3 might be an essential molecule in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.

BACKGROUND: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson's disease (PD)-like neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) via its oxidized product, 1-methyl-4-phenylpyridinium (MPP+), which is transported by the dopamine (DA) transporter into DA nerve terminals. DA receptor subtype 3 (D3 receptor) participates in neurotransmitter transport, gene regulation in the DA system, physiological accommodation via G protein-coupled superfamily receptors and other physiological processes in the nervous system. This study investigated the possible correlation between D3 receptors and MPTP-induced neurotoxicity. A series of behavioral experiments and histological analyses were conducted in D3 receptor-deficient mice, using an MPTP-induced model of PD. RESULTS: After the fourth MPTP injection, wild-type animals that received 15 mg/kg per day displayed significant neurotoxin-related bradykinesia. D3 receptor-deficient mice displayed attenuated MPTP-induced locomotor activity changes. Consistent with the behavioral observations, further neurohistological assessment showed that MPTP-induced neuronal damage in the SNpc was reduced in D3 receptor-deficient mice. CONCLUSIONS: Our study indicates that the D3 receptor might be an essential molecule in MPTP-induced PD and provides a new molecular mechanism for MPTP neurotoxicity.

A new synthesis of alpha-arbutin via Lewis acid catalyzed selective glycosylation of tetra-O-benzyl-alpha-D-glucopyranosyl trichloroacetimidate with hydroquinone.

alpha-Arbutin has huge application potentials in the cosmetic industry, as its inhibitory effect on human tyrosinase is stronger than that of its naturally occurring anomer arbutin (4-hydroxyphenyl beta-D-glucopyranoside). Enzymatic synthesis was preferred for alpha-arbutin previously, and now a new chemical synthesis is reported. The reaction of tetra-O-benzyl-alpha-D-glucopyranosyl trichloroacetimidate, as glycosyl donor, with hydroquinone was initiated by catalytic amounts of trimethylsilyl trifluoromethanesulfonate (TMSOTf), resulting in 4-hydroxyphenyl 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranoside with high stereoselectivity and yield, and then to alpha-arbutin quantitatively after deprotection.