AMPK induces PIAS3 mediated SUMOylation of E3 ubiquitin ligase Smurf1 impairing osteogenic differentiation and traumatic heterotopic ossification.

AMP-activated protein kinase (AMPK) is a typical sensor of intracellular energy metabolism. Our previous study revealed the role of activated AMPK in the suppression of osteogenic differentiation and traumatic heterotopic ossification, but the underlying mechanism remains poorly understood. The E3 ubiquitin ligase Smurf1 is a crucial regulator of osteogenic differentiation and bone formation. We report here that Smurf1 is primarily SUMOylated at a C-terminal lysine residue (K324), which enhances its activity, facilitating ALK2 proteolysis and subsequent bone morphogenetic protein (BMP) signaling pathway inhibition. Furthermore, SUMOylation of the SUMO E3 ligase PIAS3 and Smurf1 SUMOylation was suppressed during the osteogenic differentiation and traumatic heterotopic ossification. More importantly, we found that AMPK activation enhances the SUMOylation of Smurf1, which is mediated by PIAS3 and increases the association between PIAS3 and AMPK. Overall, our study revealed that Smurf1 can be SUMOylated by PIAS3, Furthermore, Smurf1 SUMOylation mediates osteogenic differentiation and traumatic heterotopic ossification through suppression of the BMP signaling pathway. This study revealed that promotion of Smurf1 SUMOylation by AMPK activation may be implicated in traumatic heterotopic ossification treatment.

Impact of inactivated COVID-19 vaccination on female ovarian reserve: a propensity score-matched retrospective cohort study.

Purpose: To explore the impact of inactivated COVID-19 vaccination on ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) concentration. Methods: A total of 3160 women were included in this single-center retrospective cohort study between June 2021 and October 2022. Vaccination information were collected from official immunization records available in personal mobile apps. Serum AMH was qualified by electrochemiluminescence immunoassay and compared with previous measurement data within three years. Women were categorized to the vaccinated group if they received two doses of inactivated COVID-19 vaccines (Sinopharm or Sinovac) between AMH tests (n = 488), and to the control group if not vaccinated (n = 2672). Propensity score matching and multivariate linear regression were performed to control for potential confounders. The main outcome measures were the numeric AMH change and percentage AMH change between the two tests. Results: There were 474 women left in each group after matching all baseline characteristics. The mean interval from the first to second AMH measurement was 508.0 ± 250.2 and 507.5 ± 253.6 days for vaccinated and unvaccinated women, respectively (P = 0.680). Both groups had a significant AMH decrease in the second test compared with the first test (P = 0.001). However, the second AMH level remained comparable between groups (3.26 ± 2.80 vs. 3.24 ± 2.61 ng/mL, P = 0.757). Similarly, no significant differences were observed in numerical (-0.14 ± 1.32 vs. -0.20 ± 1.56 ng/mL, P = 0.945) and percentage (2.33 ± 58.65 vs. 0.35 ± 48.42%, P = 0.777) AMH changes. The results were consistent in sub-analyses for women aged <35 and ≥35 years. There were also no significant differences when vaccinated women were divided according to the time interval after vaccination: ≤30, 31-60, 61-90, and ≥91 days. Conclusion: Our study provides the first evidence that inactivated COVID-19 vaccination has no measurable detrimental effect on ovarian reserve, regardless of female age and vaccination interval. This reassuring finding adds to the safety evidence of COVID-19 vaccine in fertility, and should be useful to promote vaccine acceptance. Multicenter prospective cohort studies are needed to validate our conclusion.

Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives.

Acute lung injury (ALI) describes the injury to endothelial cells in the lungs and associated vessels due to various factors. Furthermore, ALI accompanied by inflammation and thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that inflammation and the cytokine storm are main causes of ALI. Two classical anti-inflammatory cell types, regulatory T cells (Tregs) and M2 macrophages, are theoretically capable of resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs and macrophages involving their mutual activation. In this review, we discuss the current findings related to ALI pathogenesis and the role of Tregs and macrophages. In particular, we review the molecular mechanisms underlying the crosstalk between Tregs and macrophages in ALI pathogenesis. Understanding the role of Tregs and macrophages will provide the potential targets for treating ALI.

A Comparison of Three Types of "Vineyard Management" and Their Effects on the Structure of Plasmopara viticola Populations and Epidemic Dynamics of Grape Downy Mildew.

Grape downy mildew (GDM) is a destructive grapevine disease caused by Plasmopara viticola that occurs worldwide. In this study, we determined the characteristics of GDM epidemics and the grapevine canopy micro-climate in open-field, fungicide-spray, and rain-shelter plots during two constitutive years (2016 and 2017). It was found that rain shelter can significantly delay the disease occurrence by 28 and 21 days, reduce the epidemic phase by 28 and 21 days, and decrease the final disease index by 82% and 83%. Furthermore, it can block precipitation, reduce the relative humidity by 11% and 8%, and reduce the leaf wetness duration by 85% and 76% compared with open-field cultivation. A total of 3861, 783, and 1145 lesions were collected from the open-field, fungicide-managed, and rain-shelter plots, respectively, for analyses of the genetic diversity, population differentiation, and epidemic mode with seven microsatellite markers. In terms of genetic diversity, the Nei's diversity index ranged from 0.569 to 0.680 and Shannon's information index ranged from 0.958 to 1.226, showing high levels of diversity across populations. Similar to fungicide management, a rain shelter can significantly reduce the population's genetic diversity. Low pairwise FST values (0.003-0.047) and high gene flow (Nm = 1.548-20.699) were observed among the three populations each year. In addition, most of the genetic variation occurred within populations. The epidemic mode of GDM in the open-field, fungicide-managed, and rain-shelter cultivation showed moderate, low, and high levels of clonality, respectively, in the case study.