Epigenetic Regulation of WNT3A Enhancer during Regeneration of Injured Cortical Neurons.

Traumatic brain injury is known to reprogram the epigenome. Chromatin immunoprecipitation-sequencing of histone H3 lysine 27 acetylation (H3K27ac) and tri-methylation of histone H3 at lysine 4 (H3K4me3) marks was performed to address the transcriptional regulation of candidate regeneration-associated genes. In this study, we identify a novel enhancer region for induced WNT3A transcription during regeneration of injured cortical neurons. We further demonstrated an increased mono-methylation of histone H3 at lysine 4 (H3K4me1) modification at this enhancer concomitant with a topological interaction between sub-regions of this enhancer and with promoter of WNT3A gene. Together, this study reports a novel mechanism for WNT3A gene transcription and reveals a potential therapeutic intervention for neuronal regeneration.

Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells.

This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload in MC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3, and their downstream proteins were detected with Western blot assays. The results showed that the iron levels of MC3T3-E1 cells increased with increasing concentrations of FAC. High levels of ferric ion inhibited proliferation of MC3T3-E1 cells and increased their ROS levels. Additionally, iron overload induced G1arrest in MC3T3-E1 cells and down-regulated the expression of Cyclin D1 , Cyclin D3 , CDK2, CDK4 and CDK6, but up-regulated p27 Kip1. In addition, the expression levels of Beclin-1 and LC3 II increased, but that of p62 decreased. Further experiments showed that the phosphorylation of AKT and its downstream proteins p-GSK-3ß(Ser9) and p-mTOR (Ser2448) were decreased. The levels of p-p38 and p53 were up-regulated while those of cdc25A and p-ERK 1/2 were down-regulated. Phosphorylation of Stat3 and its downstream proteins was all decreased. These results show that iron overload generates ROS, blocks the PI3K/AKT and Jak/Stat3 signal pathways, and activates p38 MAPK, subsequently inducing G1 arrest and autophagy in MC3T3-E1 cells.

Customized Lingual Orthodontic Treatment of Skeletal Class II Malocclusion with Bilateral Maxillary First Premolar Extraction: Case Report.

This report describes the orthodontic camouflage treatment for a 52-year-old Chinese man using eBrace customized lingual appliance with bilateral maxillary first premolar extraction. The treatment results showed that using the eBrace customized lingual appliance can achieve expected effects and has a high level of safety for periodontal health.

Zirconia and Crofer Joint Made by Reactive Air Brazing Using the Silver Base Paste and Cu-Ti Coating Layer.

This study proposes a method to enhance the airtightness of the joint between the ZrO2 and Crofer alloy using coating technology. With the aid of vacuum sputtering technology, a titanium-copper alloy layer with a thickness between 1.5 µm and 6 µm was first deposited on the surface of ZrO2 and Crofer, respectively. The chemical composition of the deposited reaction layer was 70.2 Cu and 29.8 Ti in at%. Then, using silver as the base material in the reactive air brazing (RAB) process, we explore the use of this material design to improve the microstructure and reaction mechanism of the joint surface between ceramics and metal, compare the effects of different pretreatment thicknesses on the microstructure, and evaluate its effectiveness through air tightness tests. The results show that a coating of Cu-Ti alloy on the ZrO2 substrate can significantly improve bonding between the Ag filler and ZrO2. The Cu-Ti metallization layer on the ZrO2 substrate is beneficial to the RAB. After the brazing process, the coated Cu-Ti layers form suitable reaction interfaces between the filler, the metal, the filler, and the ceramic. In terms of coating layer thickness, the optimized 3 µm coated Cu-Ti alloy layer is achieved from the experiment. Melting and dissolving the Cu-Ti coated layer into the ZrO2 substrate results in a defect-free interface between the Ag-rich braze and the ZrO2. The air tightness test result shows no leakage under 2 psig at room temperature for 28 h. The pressure condition can still be maintained even under high-temperature conditions of 600 °C for 24 h.

Vacuum Brazing of Metallized YSZ and Crofer Alloy Using 72Ag-28Cu Filler Foil.

The study focused on dissimilar brazing of metallized YSZ (Yttria-Stabilized Zirconia) and Crofer alloy using BAg-8 (72Ag-28Cu, wt%) filler foil. The YSZ substrate was metallized by sequentially sputtering Ti (0.5/1 µm), Cu (1/3 µm), and Ag (1.5/5 µm) layers, and the Crofer substrate was coated with Ag layers with a thickness of 1.5 and 5 µm, respectively. The BAg-8 filler demonstrated excellent wettability on both metallized YSZ and Crofer substrates. The brazed joint primarily consisted of Ag-Cu eutectic. The metallized Ti layer dissolved into the braze melt, and the Ti preferentially reacted with YSZ and Fe from the Crofer substrate. The globular Fe2Ti intermetallic compound was observed on the YSZ side of the joint. The interfacial reaction of Ti was increased when the thickness of the metallized Ti layer was increased from 0.5 to 1 µm. Both brazed joints were crack free, and no pressure drop was detected after testing at room temperature for 24 h. In the YSZ/Ti(0.5µ)/Cu(1µ)/Ag(1.5µ)/BAg-8(50µ)/Ag(1.5µ)/Crofer joint tested at 600 °C, the pressure of helium decreased from 2.01 to 1.91 psig. In contrast, the helium pressure of the YSZ/Ti(1µ)/Cu(3µ)/Ag(5µ)/BAg-8(50µ)/Ag(5µ)/Crofer joint slightly decreased from 2.02 to 1.98 psig during the cooling cycle of the test. The greater interfacial reaction between the metallized YSZ and BAg-8 filler due to the thicker metallized Ti layer on the YSZ substrate was responsible for the improved gas-tight performance of the joint.

Association between early serum cholinesterase activity and 30-day mortality in sepsis-3 patients: A retrospective cohort study.

Low serum cholinesterase (SCHE) activity has been associated with poor prognoses in a variety of conditions, including sepsis. However, such an association has not been well characterized since the Third International Consensus Definitions Task Force modified the definition of sepsis to "life-threatening organ dysfunction due to a dysregulated host response to infection" (known as sepsis-3) in 2016. In the current retrospective cohort study, we examined whether 30-day mortality in sepsis-3 patients is associated with SCHE activity. A total of 166 sepsis-3 patients receiving treatment at an emergency intensive care unit (EICU) were included. The 30-day death rate was 33.1% (55/166). SCHE activity upon EICU admission was lower in nonsurvivors (3.3 vs. 4.5 KU/L in survivors, p = 0.0002). Subjects with low SCHE activity (defined as <4 KU/L) had higher 30-day mortality rates than subjects with normal SCHE activity (45.5%, 40/88 vs. 19.2%, 15/78; p<0.001). A multivariate logistic regression analysis revealed an association between 30-day mortality and lower SCHE activity after adjustments for relevant factors, such as acute multiple organ dysfunction. The odds ratio (OR) for every unit decrease in SCHE activity was 2.11 (95% confidence interval (CI), 1.37-3.27; p = 0.0008). The area under the curve (AUC) of SCHE activity for predicting 30-day mortality was 0.67 (95% CI 0.59-0.74), and the AUC of lactate for predicting 30-day mortality was 0.64 (95% CI 0.57-0.70). Using a combination of SCHE and lactate, the AUC was 0.74 (95% CI 0.69-0.83). These data suggest that lower SCHE activity is an independent risk factor for 30-day mortality in sepsis-3 patients.