Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice.

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS has gradually attracted people's attention. In this study, we constructed a PCOS mouse model through the use of dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase (POP) is a serine protease and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is its catalytic product. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. It was found that the expression of POP and Ac-SDKP was decreased in the ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-ß1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2 and high expression of TGF-ß1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-ß1 and MMP2 in vitro and inhibited ovarian fibrosis in the PCOS mouse model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP and Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.

Timing of antibiotic administration determines the spread of plasmid-encoded antibiotic resistance during microbial range expansion.

Plasmids are the main vector by which antibiotic resistance is transferred between bacterial cells within surface-associated communities. In this study, we ask whether there is an optimal time to administer antibiotics to minimize plasmid spread in new bacterial genotypes during community expansion across surfaces. We address this question using consortia of Pseudomonas stutzeri strains, where one is an antibiotic resistance-encoding plasmid donor and the other a potential recipient. We allowed the strains to co-expand across a surface and administered antibiotics at different times. We find that plasmid transfer and transconjugant proliferation have unimodal relationships with the timing of antibiotic administration, where they reach maxima at intermediate times. These unimodal relationships result from the interplay between the probabilities of plasmid transfer and loss. Our study provides mechanistic insights into the transfer and proliferation of antibiotic resistance-encoding plasmids within microbial communities and identifies the timing of antibiotic administration as an important determinant.

Type IV Pilus Shapes a 'Bubble-Burst' Pattern Opposing Spatial Intermixing of Two Interacting Bacterial Populations.

Microbes are social organisms that commonly live in sessile biofilms. Spatial patterns of populations within biofilms can be important determinants of community-level properties. Spatial intermixing emerging from microbial interaction is one of the best-studied characteristics of spatial patterns. The specific levels of spatial intermixing critically contribute to how the dynamics and functioning of such communities are governed. However, the precise factors that determine spatial patterns and intermixing remain unclear. Here, we investigated the spatial patterning and intermixing of an engineered synthetic consortium composed of two mutualistic Pseudomonas stutzeri strains that degrade salicylate via metabolic cross-feeding. We found that the consortium self-organizes across space to form a previously unreported spatial pattern (here referred to as a 'bubble-burst' pattern) that exhibits a low level of intermixing. Interestingly, when the genes encoding type IV pili were deleted from both strains, a highly intermixed spatial pattern developed and increased the productivity of the entire community. The intermixed pattern was maintained in a robust manner across a wide range of initial ratios between the two strains. Our findings show that the type IV pilus plays a role in mitigating spatial intermixing of different populations in surface-attached microbial communities, with consequences for governing community-level properties. These insights provide tangible clues for the engineering of synthetic microbial systems that perform highly in spatially structured environments. IMPORTANCE When growing on surfaces, multispecies microbial communities form biofilms that exhibit intriguing spatial patterns. These patterns can significantly affect the overall properties of the community, enabling otherwise impermissible metabolic functions to occur as well as driving the evolutionary and ecological processes acting on communities. The development of these patterns is affected by several drivers, including cell-cell interactions, nutrient levels, density of founding cells, and surface properties. The type IV pilus is commonly found to mediate surface-associated behaviors of microorganisms, but its role on pattern formation within microbial communities is unclear. Here, we report that in a cross-feeding consortium, the type IV pilus affects the spatial intermixing of interacting populations involved in pattern formation and ultimately influences overall community productivity and robustness. This novel insight assists our understanding of the ecological processes of surface-attached microbial communities and suggests a potential strategy for engineering high-performance synthetic microbial communities.

Effects of cycle periods and pressure amplitudes of alternating pressure on sacral skin blood flow responses.

BACKGROUND: There are no guidelines on selecting alternating pressure (AP) configurations on increasing sacral skin blood flow (SBF). AIM: The specific aims were to compare different cycle periods and pressure amplitudes of AP on sacral SBF responses in healthy people to establish the efficacy and safety of the protocols. METHODS: Two studies were tested, including the cycle period study (8 2.5-min vs 4 5-min protocols) and the pressure amplitude study (75/5 vs 65/15 mmHg protocols). Sacral SBF was measured using laser Doppler flowmetry (LDF) in 20 participants. AP loads were randomly applied using an indenter through the rigid LDF probe. Each protocol included a 10-min baseline, 20-min AP and 10-min recovery periods. A 30-min washout period was provided. The SBF response was normalized to the baseline SBF of each condition of each participant. RESULTS: For the cycle period study, the 4 5-min cycle protocol partially restored more SBF than the 8 2.5-min cycle protocol at the low-pressure phase (0.87 ± 0.04 vs 0.71 ± 0.03, p < 0.05) and at the high-pressure phase (0.25 ± 0.03 vs 0.19 ± 0.03, p < 0.05). For the pressure amplitude study, the 75/5 mmHg protocol partially restored more sacral SBF than the 65/15 mmHg protocol at the low-pressure phase (0.87 ± 0.1 vs 0.25 ± 0.03, p < 0.05) but not at the high-pressure phase (0.23 ± 0.02 vs 0.21 ± 0.02, non-significant). CONCLUSION: This study demonstrated that 1) a cycle period of 5 min was better than 2.5 min and 2) a pressure amplitude of 75/5 mmHg was better than 65/15 mmHg. The finding provides insights for selecting the AP configurations for increasing SBF.