Comprehensive analysis of transcriptomic profiling of 5-methylcytosin modification in placentas from preeclampsia and normotensive pregnancies.

Increasing evidence suggests that RNA m5C modification and its regulators have been confirmed to be associated with the pathogenesis of many diseases. However, the distribution and biological functions of m5C in mRNAs of placental tissues remain unknown. we collected placentae from normotensive pregnancies (CTR) and preeclampsia patients (PE) to analyze the transcriptomic profiling of m5C RNA methylation through m5C RNA immunoprecipitation (UMI-MeRIP-Seq). we discovered that overall m5C methylation peaks were decreased in placental tissues from PE patients. And, 2844 aberrant m5C peaks were identified, of which respectively 1304 m5C peaks were upregulated and 1540 peaks were downregulated. The distribution of m5C peaks were mainly located in CDS (coding sequences) regions in placental tissues of both groups, but compared with the CTR group, the m5C peak in PE group before the stop code of CDS was significantly increased and even higher than the peak value after start code in CDS. Differentially methylated genes were mainly enriched in MAPK/cAMP signaling pathway. Moreover, the up-regulated genes with hypermethylated modification were enriched in the processes of hypoxia, inflammation/immune response. Finally, through analyzing the mRNA expression levels of m5C RNA methylation regulators, we found only DNMT3B and TET3 were significantly upregulated in PE samples than in control group. And they are not only negatively correlated with each other, but also closely related to those differentially expressed genes modified by differential methylation.Our findings provide new insights regarding alterations of m5C RNA modification into the pathogenic mechanisms of PE.

Elevated Levels of Soluble Axl (sAxl) Regulates Key Angiogenic Molecules to Induce Placental Endothelial Dysfunction and a Preeclampsia-Like Phenotype.

Preeclampsia (PE), a severe pregnancy-specific syndrome, is characterized by impaired placental angiogenesis. Although the pathogenesis of this condition remains largely unclear, vascular systemic endothelial injury is thought to be the common contributing factor. Soluble Axl (sAxl), a biomarker of endothelial dysfunction, is known to be abnormally increased in a variety of diseases associated with vascular injury. In a previous study, we found that the plasma levels of sAxl were significantly higher in PE with severe features (sPE) than in pregnant women who did not have PE. The current study aimed to further explore the potential role of sAxl in vascular injury in patients with sPE. We found that the upregulation of sAxl in maternal plasma was positively correlated with the plasma levels of sFlt-1 and negatively correlated with placental NO synthase (eNOS) in women with sPE. Furthermore, elevated levels of sAxl suppressed proliferation and endothelial tube formation and promoted cytotoxicity in human umbilical vein endothelial cells (HUVECs) through the downregulation of p-Akt, p-p70S6K, p-mTOR, and Grb2. Subsequently, we established a pregnant rat model with PE-like characteristics by injecting pregnant rats with an adenovirus expressing sAxl. These rats exhibited a typical PE-like phenotype, including increased blood pressure, proteinuria, and fetal growth restriction, along with abnormal placental and fetal renal morphology. In conclusion, our study demonstrated the role of sAxl in systemic vascular injury through the regulation of the expression of key molecules of angiogenesis and described its potential contribution to the development of sPE.

Room temperature ultrafast synthesis of N- and O-rich graphene films with an expanded interlayer distance for high volumetric capacitance supercapacitors.

An electrochemical functionalization method is developed to fabricate N- and O-rich graphene films (F-RGO-60) with an expanded interlayer distance. In particular, the functionalization process could be completed within 60 seconds at room temperature, which is conducive to large-scale commercial applications. Electrochemical synthesis of F-RGO-60 leads to two synergetic effects simultaneously: (1) the expansion of the interlayer distance caused by a bubble effect, which leads to more exposure of the active surface area and (2) the introduction of N-doped sites and oxygen-containing functional groups, which not only improves the hydrophilicity of F-RGO-60 but also provides extra pseudocapacitance. It is worth mentioning that after electrochemical functionalization, F-RGO-60 can still maintain a high density of 1.47 g cm-3. Due to their optimal surface area, good electrolyte wettability and massive redox-active sites, the specific capacitance of F-RGO-60 films can reach up to 319.4 F cm-3 (217.3 F g-1) at 1 A g-1 in a three-electrode system, which is about 3.6 times larger than that of RGO films (60 F g-1). The integration of the low-cost preparation method and outstanding performance suggests that F-RGO-60 has great development prospects as supercapacitor electrode materials.

Acute Fatty Liver of Pregnancy: A Retrospective Analysis of 56 Cases.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication occurring in the third trimester. It is often fatal to both mother and fetus. The complicated clinical manifestations as well as an insufficient understanding of the disease make the precise diagnosis and effective treatment of AFLP challenging. A full understanding of the risk factors, clinical features, and test findings of AFLP is critical for its timely diagnosis and treatment. METHODS: We performed a retrospective study of 56 patients with AFLP between June 2008 and July 2013. We analyzed the clinical features, laboratory results, perioperative management, and patient outcomes. RESULTS: The initial symptoms varied considerably, with nausea and vomiting (13/56, 23%) being the most common. Liver-function indexes were remarkable, including elevated levels of serum alanine aminotransferase (262.16 ± 281.71 U/L), aspartate aminotransferase (260.98 ± 237.91 U/L), lactic dehydrogenase (1011.76 ± 530.34 U/L), and direct bilirubin (85.59 ± 90.02 µmol/L). Coagulation disorders were indicated by abnormal levels of fibrinogen (245.95 ± 186.11 mg/dL), D-dimer (2.46 ± 4.01 mg/L), and fibrin degradation products (43.62 ± 48.71 mg/L). The main maternal complications were hypoproteinemia (75%), coagulopathy (54%), and acute renal failure (39%). Multivariate logistic regression analysis identified prothrombin time (PT; odds ratio [OR] = 1.558, 95% confidence interval [CI] =1.248-1.946, PORCIP= 0.009) as risk factors. The perinatal infant death rate was related to gestational age at delivery (ORCI PORCI PORCI PConclusions: Nausea and vomiting may be the most common symptoms of AFLP. Indexes of liver dysfunction and coagulation disorders should also be considered. PT and INR are risk factors for fatal complications in patients with AFLP, and perinatal mortality is linked to the level of fibrin degradation products. Timely delivery is crucial to controlling the development of AFLP.

[Preparation and application of gel chip].

A new method for manufacturing three-dimensional gel film-coated chips was described in this paper and its advantages were evaluated by its application. A patch of polyacrylamide gel (15mm x 15mm x 20 microm) was fixed on the glass surface with Bind-Silane treatment, then activated by glutaraldehyde. The aldehyde groups in gel provided reactive sites that allowed covalent immobilization of molecules containing amino groups. Oligonucleotides were mechanically spotted by GMS 417 Arrayer. After hybridization with Cy-3 labeled probes, fluorescence signals of perfect binding can be discriminated from mismatched ones. Compared with two-dimensional glass chip, the capacity of oligonucleotides immobilized on gel film-coated chip is over 100 times. And the gel film-coated chip have lower background and shorter hybridization time. Monoclonal antibodys of cytokine IL-4, IL-5, IL-6, IL-7, ANG, I-309 and VEGF were also immobilized on the gel film-coated chips to make protein microarrays. After incubation with serum of breast cancer patients or normal persons, the microarray reacted with biotin-labeled second antibodys of cytokines and Cy-3-labeled streptavidin sequentially. Results show IL-4, IL-5, I-309 and VEGF of patients have higher expression level than normal persons. This kind of protein microarrays can be potentially helpful to clinical diagnosis. Furthermore different oligonucleotides or proteins can be performed in parallel in a single reaction with minimal amount of binding reagents. Such gel film-coated chips can be used widely in the fabrication of oligonucleotides and proteins microarrays.