Tubulin detyrosination promotes human trophoblast syncytium formation

Human trophoblast syncytialization is one of the most important yet least understood events during placental development.In this study,we found that detyrosinated a-tubulin(detyr-a-tub),which is negatively regulated by tubulin tyrosine Ugase(TTL),was elevated during human placental cytotrophoblast fusion.Correspondingly,relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells,but fusing trophoblast cells exhibited much lower levels of T T L Notably,fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL levels.Mechanistically,chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of detyra-tub.Restoration of detyr-a-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43(Cx43),which in turn promoted successful fusion between trophoblast cells.Taken together,the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and syncytialization.Insufficient tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.

Role of the proportion of dominant follicles in patients with polycystic ovary syndrome undergoing in vitro fertilization-embryo transfer

Background: There is no absolute consensus for the best time for triggering. The aim of this study was to investigate the effect of different proportion of dominant follicles (PDF) on the human chorionic gonadotropin (HCG) day for the clinical outcomes in patients with polycystic ovary syndrome (PCOS) of different ovarian stimulation protocols. Methods: A total of 371 cycles of the gonadotropin-releasing hormone (GnRH) agonist long protocol and 347 cycles of GnRH antagonist protocol from January 2014 to December 2016 were included in this retrospective study. Based on the PDF on the day of the HCG administration, the included patients were divided into three groups: Group A (low PDF), PDF <20%;Group B (medium PDF), 20%≤ PDF ≤40%;Group C (high PDF), PDF >40%. The measurements regarding ovarian stimulation characteristics, fertilization rate, top quality embryo rate, clinical pregnancy rate, and ovarian hyperstimualtion syndrome (OHSS) rate were compared in different PDF groups with different protocols. Results: In both the GnRH antagonist protocol and GnRH agonist long protocol, the characteristics such as mean age, anti-Mullerian hormone, antral follicle count (AFC), and body mass index were comparable between groups. The number of oocytes retrieved decreased statistically significantly as the PDF and rate of matured oocytes increased. In the GnRH agonist long protocol, the rate of normally fertilized oocytes was highest in Group A (59.74 ± 31.21 vs. 49.70 ± 37.95, 49.67 ± 36.62;F = 3.743, P = 0.025). There were no significant differences in the rate of top-quality embryos and the clinical pregnancy rate between the groups. The clinical pregnancy rate was similar in the three groups (63.6%, 62.5%, 67.5%, respectively,χ2 = 0.989, P = 0.911). The moderate and severe OHSS rate increased statistically significantly when the PDF increased, which was highest in group C (1.4%, 3.1%, 6.7%, respectively,χ2 = 12.014, P = 0.017). In the GnRH antagonist protocol, there were no significant differences in the rate of top-quality embryos, the rate of normally fertilized oocytes, the clinical pregnancy rate, and the moderate and severe OHSS rate between the groups. The clinical pregnancy rate in Group C was higher than that in Group A (57.9% vs. 46.6%,χ2 = 10.850, P = 0.093). Conclusions: In the GnRH antagonist protocol, PDF on the HCG day of less than 20% may be unfavorable to the clinical pregnancy rate in PCOS. In the GnRH agonist long protocol, delaying the HCG trigger timing has no good effect on clinical pregnancy and the risk of OHSS might increase in patients with PCOS.

Lagrangian analysis of the fluid transport induced by the interaction of two co-axial co-rotating vortex rings

In this paper,the fluid transport in the interaction of two co-axial co-rotating vortex rings are investigated.Vortex rings are generated using the piston-cylinder apparatus,and the resulting velocity fields are measured using digital particle image velocimetry.The interaction process is analysed by means of vorticity contour,as well by investigation of the Lagrangian coherent structures(LCSs)defined by the ridges of the finite-time Lyapunov exponent(FTLE).Experimental results demonstrate that two types of vortex interaction are identified,namely strong and weak interactions,respectively.For the strong interaction,the Lagrangian boundaries of the two vortex rings are merged together and form a flux window for fluid transport.For weak interaction,only the Lagrangian drift induced by the motion of the front vortex ring is observed and affects the Lagrangian boundary of the rear vortex ring.Moreover,the fluids transported in the strong interaction carry considerable momentum but no circulation.By contrast,there are nearly no fluxes occurring in the weak interaction.By tracking the variations of circulation and impulse occupied by the separated regions distinguished by the LCSs,it is found that the circulation nearly has no change,but the impulse occupied by vortex core region has significant change.In the strong interaction,the impulse of rear vortex ring decreases but the impulse of the front vortex ring increases.Based on the impulse law,it is speculated that the fluid force generated by the formation of the rear vortex rings can be enhanced.Therefore,the strong interaction between wake vortices can actually improve the propulsive efficiency of the biological systems by operating the formation of large-scale vortices.