Objective The role of TGF-β signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA. We hypothesized that TGF-β signaling prevents AAA by its actions on aortic medial smooth muscle cells. Approach and Results We compared the prevalence, severity, and histopathology of angiotensin II-induced AAA among control mice (no TGF-β blockade), mice with antibody-mediated systemic neutralization of TGF-β, and mice with genetically based smooth muscle-specific loss of TGF-β signaling. Surprisingly, we found that systemic—but not smooth muscle-specific—TGF-β blockade significantly increased the prevalence of AAA, and tended to increase AAA severity, adventitial thickening and aortic wall macrophage accumulation. In contrast, abdominal aortas of mice with smooth muscle-specific loss of TGF-β signaling differed from controls only in having a thinner media. We examined thoracic aortas of the same mice. Here we found that smooth muscle-specific loss of Tgfbr2—but not systemic TGF-β neutralization—significantly accelerated development of aortic pathology, including increased prevalence of intramural hematomas, medial thinning, and adventitial thickening. Conclusion Our results suggest that TGF-β signaling prevents both abdominal and thoracic aneurysmal disease but does so by distinct mechanisms. Smooth muscle-extrinsic signaling protects the abdominal aorta and smooth muscle-intrinsic signaling protects the thoracic aorta.

SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in the regulation of metabolism, stress responses, genome stability, and ageing. As a stress sensor, SIRT1 deacetylase activity is significantly increased during stresses, but the molecular mechanisms are not yet fully clear. Here, we show that SIRT1 is dynamically modified with O-GlcNAc at Ser 549 in its carboxy-terminal region, which directly increases its deacetylase activity both in vitro and in vivo. The O-GlcNAcylation of SIRT1 is elevated during genotoxic, oxidative, and metabolic stress stimuli in cellular and mouse models, thereby increasing SIRT1 deacetylase activity and protecting cells from stress-induced apoptosis. Our findings demonstrate a new mechanism for the activation of SIRT1 under stress conditions and suggest a novel potential therapeutic target for preventing age-related diseases and extending healthspan.

This study used 16S rRNA high-throughput sequencing technology to examine the differences in gut microbiota between the Père David's deer populations in the Beijing and Shishou areas of China in order to understand the effects of ex situ conservation on the intestinal microflora in the Père David's deer.Results: On the phylum level, the main bacteria found in the Père David's deer populations from both areas were similar: Firmicutes and Bacteroidetes. However, the relative abundances of the two groups were significantly different. Alpha diversity results indicated that there was a difference in the evenness of the microflora between the two groups, and the beta diversity results further indicated that there was a significant difference in the microflora structure between the two groups.Conclusions: During the ex situ conservation process of the Père David's deer, their food sources may change, resulting in differences in the gut microbiota. The intestinal microflora in the Père David's deer from the same area are clustered. Therefore, the impact of changes in food on the gut microbiota of the Père David's deer should be taken into consideration during ex situ conservation.

Analysis of the intestinal microbiota and physiological parameters in mammalian infancy can reveal health status. In this study, we used a combination of molecular and immunochemical approaches to assess fecal microbiota as well as Cortisol (Cor), Triiodothyronine (T3), and immunoglobulin A (IgA) levels of young forest musk deer (FMD), from birth to one month after weaning (7 days of age-110 days of age). During development as the diet of FMD changes from consuming milk to eating plants, the richness and diversity of intestinal microbiota of young FMD increased significantly. Cor levels remained unchanged throughout early development while significantly increased after weaning, T3 and IgA initially were derived from milk during lactation, significantly decreased after weaning. Correlation network analysis showed that the community of food-oriented microbes were highly structured and that many genera were correlated. Overall, this study provides scientific insights into effective management strategies for the protection of FMD population.

Weaning is an important event for all mammals, including young forest musk deer. However, weaning stress may cause intestinal microbiota-related disorders. Therefore, high-throughput 16S rRNA gene sequencing was applied to study the dynamic changes in intestinal microbiota during pre-weaning (10 days before weaning) and post-weaning (10 days after weaning) in 15 young forest musk deer. We saw that intestinal microbiota diversity in the post-weaning period was significantly higher than that in the pre-weaning period. The most dominant bacterial phyla were similar in the two groups (Firmicutes, Bacteroidetes and Verrucomicrobia). Meanwhile, we applied Linear discriminant analysis effect size (LefSe) to identify the most differentially microbial taxa in the pre-weaning and post-weaning groups. In the post-weaning forest musk deer, the relative abundance of Actinobacteria, Spirochaetes, Ruminococcaceae_UCG-005, Treponema and Prevotella was higher than in the pre-weaning group. However, higher relative abundance of the phyla Bacteroidetes was found in the pre-weaning group compared with that in the post-weaning group. In summary, this research provides a theoretical foundation for the dynamics of young forest musk deer intestinal microbiota during the weaning transition, which may benefit in understanding the growth and health of forest musk deer.