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Objective: To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population. Methods: Seventy-five neonates and their mothers were recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (< 3,500 g, n = 20), medium (3,500-3,999 g, n = 30) and high (≥ 4,000 g, n = 25). Placental FTO transcript levels and promoter methylation were determined by quantitative PCR and Sequenom MassARRAY®. Results: Placental FTO mRNA expression was significantly increased in the high- and medium-weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section. Conclusions: High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas. [ABSTRACT FROM AUTHOR]

The structural changes and failure mechanism of thermal barrier coatings (TBCs) during thermal shock cycling were investigated. TBCs consisting of bond coat and partially yttria-stabilized zirconia (YSZ) top coat were deposited by atmospheric plasma spraying (APS) on a nickel-based alloy substrate and its thermal shock resistance performance was evaluated. TBCs were heated at 1100°C for 15 min followed by cold water quenching to ambient temperature. Microstructural evaluation and elemental analysis of TBCs were performed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS), respectively. The crack features of YSZ coatings in TBCs during thermal shock cycling, including those of horizontal (parallel to the substrate) and vertical cracks (perpendicular to the substrate), were particularly investigated by means of SEM and image analysis. Results show that horizontal and vertical cracks have different influences on the thermal shock resistance of the coatings. Horizontal cracks that occur at the interface of YSZ and thermally growth oxidation (TGO) cause partial or large-area spalling of coatings. When vertical and horizontal cracks encounter, network segments are formed which lead to partial spalling of the coatings. [ABSTRACT FROM AUTHOR]

For the problem of identifying motion blur length, motion blur angle and defocus blur radius in mixed blur image, a method for parameter identification for mixed blur image with motion blur and defocus blur was proposed. Firstly, the blur image was processed with Fourier transformation, then Radon transformation was adopted to identify motion blur angle. Secondly, filter was adopted for the spectrum, the amplitudes in the central region of the spectrum were summed, and the sum was inputted into the BP neural network. The amplitudes were summed up vertically when estimating motion blur length and were summed up circularly when estimating defocus blur length. The simulation results show that the error of parameter identifications of noise free mixed blur images is smaller than 6%. [ABSTRACT FROM AUTHOR]

Background: Enterovirus 71 (EV71) is the main pathogen that causes severe hand, foot, and mouth disease with fatal neurological complications. However, its neurovirulence mechanism is still unclear. Candidate virulence sites were screened out at structural protein VP1, but the function of these candidate virulence sites remains unclear. Several studies have shown that autophagy is associated with viral replication. However, the relationship between VP1 and autophagy in human neurons has not been studied. Methods: A recombinant virus—SDLY107-VP1, obtained by replacing the VP1 full-length gene of the SDLY107 strain with the VP1 full-length gene of the attenuated strain SDJN2015-01—was constructed and tested for replication and virulence. We then tested the effect of the recombinant virus on autophagy in nerve cells. The effect of autophagy on virus replication was detected by western blot and plaque test. Finally, the changes of mTOR signaling molecules during EV71 infection and the effect of mTOR on virus replication at the RNA level were detected. Results: Viral recombination triggered virulence attenuation. The replication ability of recombinant virus SDLY107-VP1 was significantly weaker than that of the parent strain SDLY107. The SDLY107 strain could inhibit autophagic flux and led to accumulation of autophagosomes, while the SDLY107-VP1 strain could not cause autophagosome accumulation. The synthesis of EV71 RNA was inhibited by inhibiting mTOR. Conclusions: Replacement of VP1 weakened the replication ability of virulent strains and reduced the level of autophagy in nerve cells. This autophagy facilitates the replication of virulent strains in nerve cells. VP1 is an important neurovirulence determinant of EV71, which affects virus replication by regulating cell autophagy. mTOR is a key molecule in this type of autophagy. [ABSTRACT FROM AUTHOR]

Tetracycline (TC) is one of the most important therapeutic drugs that is widely used in hospitals. However, its harmful effects on human health and various ecosystems cannot be ignored. Owing to its poor metabolic activity and low biodegradability, TC commonly discharges as the parent compound and accumulates readily in sludges and soils by precipitation from wastewater, which can induce the evolution of antibiotic-resistant bacteria; therefore, it has been listed as one of the new pollutants with potential ecotoxicological risk. The control measures and environmental management of TC pollutants in environmental water samples require precise determination of TC pollutant concentrations. Carbon dots (CDs) are an emerging type of fluorescent material with numerous advantages such as easy preparation, low cost, low toxicity, and good biocompatibility. Consequently, they have attracted widespread attention in the field of TC detection. Herein, we synthesized TE-CDs with good blue-fluorescence performance via flow-assisted melt polymerization using tricarboxylic acid and ethylenediamine as raw precursors. The morphology and structure of the prepared TE-CDs were characterized. The transmission electron microscopy (TEM) results showed that the prepared TE-CDs were well dispersed, with an average diameter of (2.43±0.48) nm. The X-ray diffraction (XRD) results showed that the TE-CDs had an amorphous carbon structure. Infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) characterizations showed that the surface of the TE-CDs was rich in hydrophilic groups, such as amino, hydroxyl, and carboxyl groups, which indicated that TE-CDs had good water solubility and were advantageous for detecting TC in medical wastewater. Subsequently, the optical properties of the TE-CDs were investigated. The fluorescence emission spectra of the TE-CDs were recorded at various excitation wavelengths. The emission spectra of the TE-CDs exhibited excitation wavelength dependence and when the excitation wavelength changes from 300 nm to 400 nm, their fluorescence intensity decreased to varying degrees. The TE-CDs exhibited optimal fluorescence intensity at an excitation wavelength of 368 nm, while the emission wavelength was 448 nm. TC could effectively quench the blue fluorescence of the CDs, and by utilizing this property, the detection of TC concentration could be achieved. After the addition of TC, the fluorescence of the system immediately reached an extreme value, and no significant change was observed within 10 min. An incubation time of 20 s was selected to obtain precise results. Additionally, the TE-CDs exhibited stable fluorescence intensity over a wide pH range. The fluorescence stability of the TE-CDs was investigated, and no significant change in fluorescence intensity was observed after standing for 10 d, indicating that the prepared TE-CDs had excellent fluorescence stability. The fluorescence intensity of the TE-CDs decreased to varying degrees within the range of 2-200 mg/L TC until complete quenching occurred. TC mass concentration in the range of 4-20 mg/L showed a good linear relationship ( R 2 =0.9978) with the fluorescence quenching intensity of the TE-CDs. The limit of detection was 0.2 mg/L. A preliminary investigation was undertaken to explore the quenching mechanism of the TE-CDs fluorescence by TC. Upon addition of TC, a significant reduction in the fluorescence lifetime of the TE-CDs was observed. During the quenching process, no new substances were observed by UV absorption spectroscopy. Additionally, no significant changes in the 1 H NMR spectra of the TE-CDs were noted before and after the addition of TC, indicating the absence of an interaction between the TE-CDs and TC. Therefore, the quenching mechanism may involve dynamic quenching. The selectivity and anti-interference ability of the developed method were evaluated; in the presence of interfering substances, TC quenched the fluorescence of the TE-CDs, indicating that the TE-CDs had good selectivity and anti-interference performance towards TC. The method was applied to the quantitative detection of TC in medical wastewater, with recoveries of 96.5%-119.8% and relative standard deviations of 0.8%-2.6%. In conclusion, the analytical performance of the proposed method is comparable with that of previously reported detection methods; moreover, the method has the advantages of low operational cost, simple preparation process, time-saving, and good repeatability. Therefore, the TE-CDs can be used as chemical sensors for the detection of TC in medical wastewater and have good practical applications.

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.

Background: The purpose of the present study was to determine a statistically valid cutoff score for the Zarit Burden Interview (ZBI) in order to identify family caregivers at risk for depression and anxiety to guide for further assessment and future intervention., Methods: The ZBI, the Patient Health Questionnaire (PHQ), and the Generalized Anxiety Disorder Scale (GAD) were administered to a representative community sample of 327 family caregivers of schizophrenia individuals. A ZBI cutoff score was determined using three different statistical methods: tree-based modeling, K-means clustering technique and linear regression, followed by contingency analysis and receiver operating characteristic (ROC) curve to compare between depression and anxiety scale scores with the ZBI cutoff., Results: Findings suggest that a cutoff score of 48 in ZBI has significant predictive validity for identifying caregivers at risk for both depression and anxiety. A ZBI cutoff of 48 showed sensitivity of 73% for PHQ and 70% for GAD, specificity of 80% for PHQ and 79% for GAD, PPV (positive predictive value) of 75% for PHQ and 73% for GAD, NPV (negative predictive value) of 78% for PHQ and 76% for GAD., Conclusions: This cutoff score would enable health care providers to assess family caregivers at risk and provide necessary interventions to improve their quality of life in this important role.

Enterovirus A71 (EV-A71) is known for its manifestation as hand foot and mouth disease (HFMD), which has caused countless large-scale epidemic outbreaks throughout the world. However, the molecular pathogenesis of EV-A71 infection is still elusive. Previous studies found that the biological characteristics of a mild EV-A71 strain (SDLY1) and a severe EV-A71 strain (SDLY107) are significantly different, and sequence analysis showed that there are several differences in nucleotide sites of UTRs (88 nt, 123 nt, 143 nt, 154 nt, 187 nt, 241 nt, 243 nt, 253 nt, 291 nt, 438 nt, 440 nt, 571 nt, 579 nt, 602 nt, 658 nt, 664 nt, 690 nt, 696 nt, 7328 nt, 7335 nt, 7367 nt, and 7395 nt). The aim of this study was to determine whether these amino sites in UTRs are associated with the pathogenesis of EV-A71 and are responsible for different clinical manifestations. Based on the reverse genetics technology, we rescued two chimeric viruses SDLY107(1-5'UTR) and SDLY107(1-3'UTR) by replacing 5'UTR/3'UTR gene fragments of an infectious cDNA clone. Replication kinetics and cytotoxicity assays showed that the virulence of the two chimeric strains significantly changed in vitro. The viral loads of the two chimeric strains in infected ICR mice were reduced and pathological damage in the brains, lungs, intestinal tissues, and muscles were lightened. Our findings suggest that some nucleotide sites in UTRs may have a function in the pathogenicity and virulence of EV-A71., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess the prevalence and severity of voice symptoms in individuals with a diagnosis of autoimmune disease., Study Design: Cross-sectional survey., Setting: Study participants were recruited from a rheumatology tertiary referral clinic at Norfolk and Norwich University Hospital., Subjects and Methods: A cross-sectional questionnaire analyzing 109 patients with autoimmune disease (rheumatoid arthritis, seronegative spondyloarthritis, connective tissue disease) and a control group of 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis). Main outcome measures were the Voice Handicap Index-10 (VHI-10), xerostomia scale, acid reflux inquiry, and anxiety/depression scale., Results: Patients with autoimmune disease were more likely to experience voice symptoms as assessed by the VHI-10 questionnaire (P = .0035). Subgroup analysis showed autoimmune patients were more likely to report voice symptoms regardless of whether they were on a disease-modifying antirheumatic drug (DMARD; P = .0010) or non-DMARD (P = .017), suggesting autoimmune disease may be an independent risk factor from pharmacotherapy. Xerostomia was more common in an autoimmune population compared with the control group (P = .02). A positive correlation between xerostomia and VHI-10 scores was found for the DMARD group (Spearman rank coefficient = 0.49, P < .001). No significant difference in acid reflux inquiry (P = .44) or the anxiety/depression scale (P = .36) was found when comparing the autoimmune and control groups., Conclusion: Patients with autoimmune disease have increased likelihood of voice symptoms when compared with a control population with non-autoimmune disease. Further prospective studies to elucidate the cause of voice disorder would be valuable.

The field of liver transplantation is limited by the availability of donor organs. The use of living donor and split cadaveric grafts is one potential method of expanding the donor pool. However, primary graft dysfunction can result from the use of partial livers despite the absence of other causes such as vascular obstruction or sepsis. This increasingly recognised phenomenon is termed "Small-for-size syndrome" (SFSS). Studies in animal models and humans have suggested portal hyperperfusion of the graft combined with poor venous outflow and reduced arterial flow might cause sinusoidal congestion and endothelial dysfunction. Graft related factors such as graft to recipient body weight ratio < 0.8, impaired venous outflow, steatosis > 30% and prolonged warm/cold ischemia time are positively predictive of SFSS. Donor related factors include deranged liver function tests and prolonged intensive care unit stay greater than five days. Child-Pugh grade C recipients are at relatively greater risk of developing SFSS. Surgical approaches to prevent SFSS fall into two categories: those targeting portal hyperperfusion by reducing inflow to the graft, including splenic artery modulation and portacaval shunts; and those aiming to relieve parenchymal congestion. This review aims to examine the controversial diagnosis of SFSS, including current strategies to predict and prevent its occurrence. We will also consider whether such interventions could jeopardize the graft by compromising regeneration.