Microtubule affinity regulating kinase 4 (MARK4) plays a crucial role in the regulation of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation, which leads to the generation of bioactive interleukin (IL)-1β and IL-18. E74-like ETS transcription factor 3 (ELF3) participates in endothelial inflammatory processes. We hypothesized that ELF3 modulates MARK4 expression in vascular endothelial cells, thus contributing to high glucose-mediated NLRP3 inflammasome activation. Plasma IL-1β, IL-18, NLRP3 inflammasome and MARK4 expression was increased in diabetic patients and rats. An in vitro study indicated that high glucose increased IL-1β and IL-18 expression and activated the NLRP3 inflammasome via upregulation of MARK4 in human umbilical vein endothelial cells (HUVECs). Furthermore, high glucose increased ELF3 expression. ELF3 downregulation reversed the effects of high glucose treatment. Accordingly, the effects of ELF3 overexpression were similar to those of high glucose treatment and were counteracted by siMARK4. Furthermore, ELF3 was found to interact with SET8. High glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. Overexpression of SET8 inhibited high glucose-induced MARK4 expression and NLRP3 inflammasome activation. The effects of shSET8 were similar to those of high glucose treatment and were counteracted by siMARK4. A mechanistic study found that ELF3 and H4K20me1 were enriched in the MARK4 promoter region. si-ELF3 attenuated MARK4 promoter activity and augmented the inhibitory effect of SET8 on MARK4 promoter activity. Furthermore, SET8 downregulation and ELF3 upregulation were confirmed in diabetic patients and rats. In conclusion, ELF3 interacted with SET8 to modulate MARK4 expression, which participated in hyperglycaemia-mediated endothelial NLRP3 inflammasome activation.
Background Aroma is one the most crucial inherent quality attributes of fruit. ‘Ruixue’ apples were selected from a cross between ‘Pink Lady’ and ‘Fuji’, a later ripening yellow new cultivar. However, there is little known about the content and composition of aroma compounds in ‘Ruixue’ apples or the genetic characters of ‘Ruixue’ and its parents. In addition, the metabolic pathways for biosynthesis of aroma volatiles and aroma-related genes remain poorly understood. Results Volatile aroma compounds were putatively identified using gas chromatography-mass spectrometry (GC–MS). Our results show that the profile of volatile compounds changes with ripening. Aldehydes were the dominant volatile compounds in early fruit development, with alcohols and esters increasing dramatically during maturation. On the basis of a heatmap dendrogram, these aroma compounds clustered into seven groups. In ripe fruit, esters and terpenoids were the main aroma volatiles in ripening fruit of ‘Pink Lady’ and ‘Fuji’ apples, and they included butyl 2-methylbutanoate; propanoic acid, hexyl ester; propanoic acid, hexyl ester; hexanoic acid, hexyl ester; acetic acid, hexyl ester and (Z, E)-α-farnesene. Interestingly, aldehydes and terpenoids were the dominant volatile aroma compounds in ripening fruit of ‘Ruixue’, and they mainly included hexanal; 2-hexenal; octanal; (E)-2-octenal; nonanal and (Z, E)-α-farnesene. By comparing the transcriptome profiles of ‘Ruixue’ and its parents fruits during development, we identified a large number of aroma-related genes related to the fatty acid, isoleucine and sesquiterpenoid metabolism pathways and transcription factors that may volatile regulate biosynthesis. Conclusions Our initial study facilitates a better understanding of the volatile compounds that affect fruit flavour as well as the mechanisms underlying differences in flavour between ‘Ruixue’ and its parents.
This study aimed to observe the effects of lung-protective ventilation (LPV) on oxygenation index (OI) and postoperative pulmonary complications (PPCs) after laparoscopic radical gastrectomy in middle-aged and elderly patients. A total of 120 patients who were scheduled to undergo laparoscopic radical gastrectomy with an expected time of >3 h were randomly divided into conventional ventilation (CV group) with tidal volume (TV) of 10 mL/kg without positive end-expiratory pressure (PEEP), and lung-protective ventilation (PV group) with 7 mL/kg TV and personal level of PEEP with regular recruitment maneuver every 30 min. Measurements of OI, modified clinical pulmonary infection score (mCPIS), and PPCs were assessed during the perioperative period. Fifty-seven patients in the CV group and 58 in the PV group participated in the data analysis. Patients in the PV group showed better pulmonary dynamic compliance, OI, and peripheral capillary oxygen saturation during and after surgery. The mCPIS was significantly lower in the PV group than in the CV group after surgery. The incidence rate of PPCs was lower in the PV group than in the CV group and the difference was significant in patients whose ventilation time was longer than 6 h in both groups. LPV during laparoscopic radical gastrectomy significantly improved pulmonary oxygenation function and reduced postoperative mCPIS and the incidence of PPCs during the early period after surgery of middle-aged and elderly patients, especially patients whose mechanical ventilation time was longer than 6 h.
Aroma is an important quality indicator for apples and has a great influence on the overall flavour and consumer acceptance. However, the information of the aroma volatile compounds in apple peels is largely unknown. In this study, evaluation of volatile compounds in peels of 40 apple cultivars was carried out using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). A total of 78 volatile compounds were identified, including 47 esters, 12 aldehydes, 5 alcohols, 3 ketones, 1 acid and 10 others. Eight volatile compounds were common in all apple cultivars. Cultivar Changfu No. 2 contained the highest number of volatile compounds (47), while Qinyue contained the least (20). Honey Crisps had the highest volatile content, at 27,813.56 ± 2310.07 µg/kg FW, while Huashuo had the lowest volatile content, at 2041.27 ± 120.36 µg/kg FW. Principal component analysis (PCA) clustered the 40 apple cultivars into five groups. Aroma is cultivar-specific, volatile compounds of hexyl butyrate, hexyl 2-methylbutyrate and hexyl hexanoate, together with hexanal, (E)-2-hexenal, 1-hexanol, estragole and α-farnesene could be proposed for apple cultivar classification in the future.
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