ABSTRACT The rumen of neonatal calves is not well-developed and exhibits limited functionality. Therefore, the establishment of intestinal microbiota may play an instrumental role in their health and performance, but it has been rarely explored. Thus, we aim to explore the temporal colonization of the gut microbiome and the potential benefits of early microbial intervention in newborn calves. We followed up on the temporal dynamics of the gut microbiome and plasma metabolome in 36 newborn calves during the first two months of life and established their relationships with their health status and performance. We also evaluated whether microbiota transplantation (MT) could influence their phenotypes by modulating metabolism and its impact on later milk production performance.We showed that the composition and ecological interactions of the gut microbiome are likely to reach maturity one month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion, antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. The data from the study may help develop strategies to manipulate the gut microbiota during early life, which may be significantly relevant to the health and production of newborn calves. HIGHLIGHTS The gut microbial composition and ecological interaction in newborn calves reach maturity one month after birth Temporal shifts in the gut microbiome of newborn calves are associated with phenotypic changes, including growth, digestion, and antioxidative capacity Early microbial intervention in newborn calves reduces diarrhea while improving later milk production The gut microbial impact on newborn calves is mediated by plasma metabolites
Objective
To investigate the feasibility and effect of visualization teaching method using HC visual laryngoscope for the standardized training of endotracheal intubation in emergency department.
Methods
Forty standard-trainee doctors were divided into two groups randomly. 20 standard-trainee doctors in team N were taught using the conventional teaching method of emergency medicine for the standardized training of endotracheal intubation, and the other 20 standard-trainee doctors in team HC were taught by visualization teaching method using HC visual laryngoscope. After 1 month training, comparisons of the success rate of tracheal intubation in airway management simulator, the time consumed for intubation and the number of attempt on successful intubation cases, and the satisfaction score with the teaching mode scored by standard-trainee doctors between the two groups were done.
Results
The one-attempt success rate and the success rate of tracheal intubation in airway management simulator by the standard-trainee doctors in group HC were significantly higher than those in group N (40% vs. 10%, 85% vs. 55%), while the number of attempt and the time consumed for successful intubation were significantly less than those in group N[ (1.65±0.61) vs. (2.27±0.66), (79.00±8.35) s vs. (89.36±12.03) s). The satisfaction score with this teaching mode and teaching effect of standard-trainee doctors in group HC were significantly higher than those in group N (8.10±0.74 vs. 6.55±1.05, 8.15±0.80 vs. 6.85±0.91).
Conclusions
The visualization teaching method with application of HC visual laryngoscope for standardized training of endotracheal intubation in emergency department could improve the success rate and efficiency of tracheal intubation in airway management simulator for standard-trainee doctors, and this teaching method may be better than the conventional teaching method on teaching mode presenting some feasibility.
Key words:
HC visual laryngoscope; Visualization teaching; Endotracheal intubation; Emergency department; Standardized training; Teaching
To further understand the role of growth regulation of human ovarian cancer cells by transforming growth factor (TGF) beta 1.The cell proliferation, cAMP synthesis, gene expression, and induction of programmed cell death (PCD) in human epithelial ovarian cancer cell line HO-8910 cells exposed to TGF beta 1 in vitro were studied.TGF beta 1 inhibited cell growth and DNA synthesis, and induced G0/G1 arrest in cell cycle. It could also trigger PCD in cells. This induction of PCD may occur within G0/G1 phase. Meanwhile, the assay also showed that TGF beta 1 could inhibit the mRNA expression of c-myc, EGFR and TGF beta 1 genes in cells.TGF beta 1 can not only act as an autocrine to inhibit cell proliferation, but also trigger PCD in HO-8910 cells. These functions may be fulfilled through some specific signal transduction pathways.
Abstract Ensuring genome safety during gene editing is crucial for clinical translation of the high-efficient CRISPR-Cas9 toolbox. Therefore, the undesired events including chromosomal translocations, vector integrations, and large deletions arising during therapeutic gene editing remain to be adequately addressed or tackled in vivo. Here, we apply CRISPR-Cas9TX in comparison to CRISPR-Cas9 to target Vegfa for the treatment of age-related macular degeneration (AMD) disease in a mouse model. AAV delivery of both CRISPR-Cas9 and CRISPR-Cas9TX can efficiently inhibit laser-induced neovascularization. Importantly, Cas9TX almost eliminates chromosomal translocations that occur at a frequency of approximately 1% in Cas9-edited mouse retinal cells. Strikingly, the widely observed AAV integration at the target Vegfa site is also greatly reduced from nearly 50% of edited events to the background level during Cas9TX editing. Our findings reveal that chromosomal structural variations routinely occur during in vivo genome editing and highlight Cas9TX as a superior form of Cas9 for in vivo gene disruption.
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