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Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen–glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel. [ABSTRACT FROM AUTHOR]

As health improvement is paid increased attention, the research on small ruminant milk is becoming more prevalent. Studies have shown that the nutrient content in sheep milk is higher than goat and cow milk. This study aimed to explain the difference of Small-Tailed Han (STH) and DairyMeade (DM) milk through the untargeted metabolomics analyze with ultra-high-performance liquid tandem chromatography quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF–MS). The results showed that fat, protein, casein, solids of STH milk were higher than DM, but the lactose of it was lower than DM. The metabolomics analysis showed that 4904 annotated metabolites were identified and 68 significantly different metabolites between milks were detected. 47 metabolites in the STH were significantly higher than the DM and 21 metabolites were significantly lower than the DM. The significantly different metabolites were mainly enriched in glycerophospholipid metabolism, glycosyl phosphatidyl inositol (GPI)-anchor biosynthesis, regulation of autophagy, and purine metabolism. We hypothesized that the high level of phospholipids in STH milk may lead to higher fat content than DM milk; the high level of L-Carnitine would enhance the lipid metabolism and further lead to lower milk fat of DM milk. The high level of nucleotides and their derivatives in DM milk may be related with its high milk production performance. It demonstrated that the composition of the sheep milk changed with breeds. Furthermore, the interactions and metabolic pathways were analyzed to explore the mechanisms related to different lactation traits between two breeds. This study would provide theoretical basis for later dairy sheep breeding. [ABSTRACT FROM AUTHOR]

Cytosine and adenine base editors are promising new tools for introducing precise genetic modifications that are required to generate disease models and to improve traits in pigs. Base editors can catalyze the conversion of C→T (C>T) or A→G (A>G) in the target site through a single guide RNA. Injection of base editors into the zygote cytoplasm can result in the production of offspring with precise point mutations, but most F0 are mosaic, and breeding of F1 heterozygous pigs is time-intensive. Here, we developed a method called germinal vesicle oocyte base editing (GVBE) to produce point mutant F0 porcine embryos by editing the maternal alleles during the GV to MII transition. Injection of cytosine base editor 3 (BE3) mRNA and X-linked Dmd-specific guide RNAs into GVoocytes efficiently edited maternal Dmd during in vitro maturation and did not affect the maturation potential of the oocytes. The edited MII oocytes developed into blastocysts after parthenogenetic activation (PA) or in vitro fertilization (IVF). However, BE3 may reduce the developmental potential of IVF blastocysts from 31.5%±0.8% to 20.4% ±2.1%. There 40%–78.3% diploid PA blastocysts had no more than two different alleles, including up to 10% embryos that had only C>T mutation alleles. Genotyping of IVF blastocysts indicated that over 70% of the edited embryos had one allele or two different alleles of Dmd. Since the male embryos had only a copy of Dmd allele, all five (5/19) F0 male embryos are homozygous and three of them were Dmd precise C>T mutation. Nine (9/19) female IVF embryos had two different alleles including a WT and a C>T mutation. DNA sequencing showed that some of them might be heterozygous embryos. In conclusion, the GVBE method is a valuable method for generating F0 embryos with maternal point mutated alleles in a single step. [ABSTRACT FROM AUTHOR]

Background: The development efficiency of cloned cattle is extremely low (< 5%), most of them were aborted at late gestation. Based on our previous studies, some recipient cows with a cloned fetus would present as engorged uterine vessels and enlarged umbilical vessels randomly. Abortion involves both maternal and fetal factors. Objective: Our aim was to explore this phenomenon by microRNAs expression profile analysis of maternal corpus luteum (CL), which was related to pregnancy maintenance. Methods: The present study provided the comparison of maternal CL miRNAs expression of abnormally and normally developed cloned bovine fetus at late gestation (~ 210 days) using RNA-Seq technology. Results: We selected two abnormally pregnant cows (abnormal group, AG) and three normally pregnant cows (normal group, NG) and acquired valid reads of 9317,261–12,327,185 (~ 84.53–91.28%) from five libraries. In total, we identified 981 conserved miRNAs and 223 novel miRNAs. 1052 miRNAs were co-expressed, 124 miRNAs were uniquely expressed in AG, and 93 miRNAs were uniquely expressed in the NG. Compared with NG, 11 were significantly overexpressed, and 22 were downregulated (p < 0.05) at AG among 1052 co-expressed miRNAs. The differentially expressed miRNAs-targeted genes were further analyzed by Gene Ontology and KEGG pathway analysis. Notably, the steroid biosynthesis pathway was a significantly enriched term (p < 0.01), which may affect the secretion of progesterone. Conclusion: Our research suggested that abnormal miRNAs expression of bovine maternal CL may affect the pregnant status at late gestation. [ABSTRACT FROM AUTHOR]

The dysfunction of placenta is common in somatic cell nuclear transfer (SCNT) cloned cattle and would cause aberrant fetal development and even abortion, which occurred with highest rate at the mid- to late gestation. However, the mechanism of abnormal placentas was unclear. To analyze the transcriptome-wide characteristics of abnormal placentas in SCNT cloned cattle, the mRNA, lncRNA and miRNA of placental cotyledon tissue at day 180 after gestation were sequenced. A total of 19,055 mRNAs, 30,141 lncRNAs and 684 miRNAs were identified. Compared with control group, 362 mRNAs, 1,272 lncRNAs and nine miRNAs (six known and three novel miRNAs) were differentially expressed (fold change ≥ 2 and P-value < 0.05). The differentially expressed genes were functionally enriched in urea and ions transmembrane transport, which indicated that the maternal-fetal interactions were disturbed in impaired placentas. Furthermore, the competing endogenous RNAs (ceRNAs) networks were identified to illustrate their roles in abnormal placental morphology. The present research would be helpful to discover the mechanism of late gestational abnormality of SCNT cattle by provides important genomic information and insights. [ABSTRACT FROM AUTHOR]