Mitochondrial DNA methylation drift and postoperative delirium in mice.

BACKGROUND: Mitochondrial dysfunction is linked to the etiopathogenesis of postoperative delirium (POD), which severely affects the prognosis of elderly patients undergoing surgery. The methylation of mitochondrial DNA (mtDNA), a new and incompletely described phenomenon that regulates the structure and function of mitochondria, is associated with ageing. However, the relationship between mtDNA methylation and POD has not been established. OBJECTIVE: To explore the potential roles of mitochondrial epigenetic regulation in POD. DESIGN: A randomised animal study. PARTICIPANTS: Eighty-eight 6-month-old and one hundred seventy-six 18-month-old male C57BL/6N mice. INTERVENTIONS: POD was induced by abdominal surgery under 1.4% isoflurane for 2 h. Behavioural tests were performed at 24 h before surgery and at 6, 9 and 24 h after surgery. MAIN OUTCOME MEASURES: 5-methylcytosine (5-mC) at five CpG sites of the displacement loop (D-loop) and at 60 CpG sites of coding gene loci in the mitochondrial genome after surgery of the hippocampus, prefrontal cortex, amygdala and anterior cingulate cortex in 6 and 18-month-old mice were detected using bisulfite pyrosequencing. Mitochondrial structure, mitochondrial gene expression and mtDNA copy number were also examined using Electron microscopy and real time PCR to find the association with mtDNA methylation. RESULTS: The mtDNA methylation drift manifested as a decrease in the methylation levels at the D-loop and an increase or decrease in the methylation levels at several coding gene loci, ultimately resulting in reduced mtDNA copy numbers, altered mitochondrial gene expression and damaged mitochondrial structures in the hippocampus and prefrontal cortex after surgery. The activation of Silent information regulator-1 (SIRT1) ameliorated anaesthesia-induced and surgery-induced mitochondrial dysfunction and delirium-like behaviours by regulating mtDNA methyltransferase-mediated mtDNA methylation. CONCLUSION: These data support the existence of epigenetic mtDNA regulation in POD; however, further studies are required to explore the specific mechanisms. TRIAL REGISTRATION: No 20181204 Drum tower hospital.

[Prenatal screening and diagnosis for a fetus with mosaic sex chromosome abnormality].

OBJECTIVE: To carry out prenatal screening and diagnosis for a woman with advanced maternal age. METHODS: Non-invasive prenatal testing (NIPT) was carried out to determine the risk of fetal chromosome aneuploidy. Aminiocentesis was proceeded for fetal chromosomal karyotyping and copy number variation sequencing (CNV-seq). The fetus was subjected to systematic ultrasound screening in the second trimester. RESULTS: NIPT has indicated there was a loss of fetal sex chromosome. Karotyping of the amniocyte showed a mosaic sex chromosome abnormality 45,X[53]/46,X,+mar[7]. The result of fetal DNA CNV-seq was seq[GRCh37]del(Yq11.1q12) chrY: g.13 104 553-28 819 361del, seq[GRCh37]del(Yp11.32p11.2) chrY: g.10 001-9 873 915del (mosaic ratio: 30%). Ultrasonography discovered that the fetus had renal dysplasia and male external genitalia. The karyotypes of the couple were both normal. CONCLUSION: Multiple genetic tests should be carried out for fetus with a high risk for chromosome aneuploidies signaled by NIPT. It is difficult to predict the post-natal phenotype for fetuses with mosaic sex chromosomal aneuploidies. The couple should be carefully counseled upon genetic counseling.

Water Stable Heterometallic Zn-Tb Coordination Polymer for Rapid Detection of the Ultraviolet Filter Benzophenone.

Benzophenone (BP) is an ultraviolet filter (UVF) widely used in personal care products such as sunscreens and cosmetics. Excessive exposure to BP-type UVFs is a potential threat to human's health because of their endocrine-disrupting activity. Water stability of lanthanide compounds is crucial when they serve as luminescent sensors because of the practicality and recyclability. In this study, a water-stable luminescent Zn-Tb heterometallic coordination polymer was rationally designed and synthesized for rapid detection of BP. This material showed a high quenching effect, excellent selectivity, and fast response toward BP.

[Identification of metabolites of Chenxiang Huaqi pill in rats based on UPLC-Q-TOF-MS].

To analyze the metabolites of Chenxiang Huaqi pill in rats by using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). The separation was performed on Phenomenex Kinetex C18 column, with the acetonitrile -0.1% formic acid as the mobile phase for gradient elution at a flow rate of 0.8 mL·min⁻¹. The data were collected by the positive ion mode of ESI source. The plasma and urine total ion chromatograms of the rats in blank group and treatment group were used to analyze the targeted ion chromatograms. The results showed that 24 compounds were detected in the plasma and urine, including 5 prototype components and 19 metabolites. The major metabolic pathways included hydration, glucuronidation, demethylation, hydrolysis, hydroxylation and sulfation. The method was rapid, simple and sensitive, and can be used to rapidly identify the metabolites of Chenxiang Huaqi pill that can be absorbed in rats, providing a reference for the study of the absorption and metabolism mechanism of Chenxiang Huaqi pill in vitro.

[Effects of Atractylodes macrocephala monosaccharide composition on cytodifferentiation and villin expression of IEC-6 cells in vitro].

OBJECTIVE: To study the influence of Atractylodes macrocephala monosaccharide composition (AMMC) on IEC-6 cells by observing cytodifferentiation and expression of villin. METHOD: Observed cell morphous under light microscope, observed cell ultramicrostructure under transmission electron microscope, evaluated villin mRNA by way of RT-PCR, and detected protein of villin by immunofluorescence. Cells were divided into the groups including blank control,positive control (given with gastrin 250 microg/L) and AMMC groups (given with AMMC 62.5, 125, 250, 500, 1000 mg/L respectively). RESULTS: 1. Cells in blank control group were immature under light microscope, which were in state of differentiation in groups with gastrin and different concentration of AMMC. 2. Cells in blank control group had bigger nucleuses with higher ratio of heterochromatin and much less villin at the edge of cells, which in groups with gastrin and different concentration of AMMC had smaller nucleuses with normal ratio of heterochromatin/heterochromatin and abundance of villin at the edge of cells. 3. Villin mRNA of IEC-6 cells in groups with gastrin and different concentration of AMMC were obviously much more than that of cells in blank control group 6 h afeer treatment. 4. Little protein of villin was detected by immunofluorescence in blank control group, which was much brighter in group with gastrin, and less bright in group with different concentration of AMMC, in which specific villin assembled. CONCLUSION: AMMC can promote cytodifferentiation by up-regulating the expression and distribution of villin in IEC-6 cells.

Reversible structural transformation induced switchable single-molecule magnet behavior in lanthanide metal-organic frameworks.

Switchable "on/off" single-molecule magnet (SMM) behavior can be realized in lanthanide metal-organic frameworks (Ln-MOFs) tuned by the temperature-induced change of the coordination geometry of the lanthanide centers.