Expression of TET and 5-HmC in Trophoblast Villi of Women with Normal Pregnancy and with Early Pregnancy Loss

Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy. The ten-eleven translocation （TET） family and 5-hydroxymethylcytosine （5-hmC） were found to be linked with epigenetic reprogramming. The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss （EPL）. Embryonic villi were collected from normal pregnant women （control） experiencing medical abortion and from EPL patients at gestation ages of 6, 7 and 8 weeks. The mRNAs of TET family were analysed using quantitative polymerase chain reaction （qPCR）, and TET proteins using Western blotting and immunohistochemical analysis. The MethylFlashTM Kit was used to quantify the absolute amount of 5-methylcytosine （5-mC） and 5-hmC. Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age. Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples, which was consistent with the qPCR and Western blot results. The expression of TET1, TET2, and TET3 was lower in the villi in EPL group than in normal pregnancy group （P〈0.05 for all）. It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo. The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL.

Longitudinal impedance measurements and simulations of a three-metal-strip kicker

A kicker is a critical component for beam injection and accumulation in circular particle accelerators. A ceramic slat kicker plated with a TiN conductive coating was applied in the Beijing Electron Positron Collider (BEPCII). However, the ceramic slat kicker has experienced several sudden malfunctions during the operation of the BEPCII in the past. With a reliable kicker structure, a three-metal-strip kicker can substitute the original ceramic slat kicker to maintain the operational stability of the BEPCII. A comparison of the numerical simulation was conducted for three kicker models, demonstrating the comprehensive advantage of the three-metal-strip kicker. Furthermore, impedance bench measurements were conducted on a prototype of a three-metal-strip kicker. The longitudinal beam-coupling impedance was measured using a vector network analyzer via the coaxial wire method. A satisfactory agreement was obtained between the numerical simulations and measurements. Based on the numerical simulation data, the loss factor was 0.01721 V/pC, and the effective impedance was 3.59 mΩ(σ=10 mm).The simulation of the heat deposition on each part of the kicker demonstrated that 84.4%of the parasitic loss of the beam was deposited on the metal strips, and the total heat deposition power on the kicker was between 113.3 and 131.5 W. The obtained heat deposition powers can be considered as a reference for establishing the cooling system.

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease(MASLD),the absence of licensed medications is striking.A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications.MASLD therapies center on four major pathways.Considering the close relationship between MASLD and type 2 diabetes,the first approach involves antidiabetic medications,including incretins,thiazolidinedione insulin sensitizers,and sodium-glucose cotransporter 2 inhibitors.The second approach targets hepatic lipid accumulation and the resultant metabolic stress.Agents in this group include peroxisome proliferatoractivated receptor agonists(e.g.,pioglitazone,elafibranor,saroglitazar),bile acid-farnesoid X receptor axis regulators(obeticholic acid),de novo lipogenesis inhibitors(aramchol,NDI-010976),and fibroblast growth factor 21/19 analogs.The third approach focuses on targeting oxidative stress,inflammation,and fibrosis.Agents in this group include antioxi-dants(vitamin E),tumor necrosis factor a pathway regulators(emricasan,pentoxifylline,ZSP1601),and immune modulators(cenicriviroc,belapectin).The final group targets the gut(IMM-124e,solithromycin).Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects.This review aimed to provide an update on these medications.