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Objective: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age., Methods: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China., Results: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients., Conclusion: In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Objectives: To investigate clinical and microbiological response, and 30-day mortality of pneumonia involving multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex treated with colistin, and identify associated factors of these outcomes., Methods: A retrospective study of 183 adult patients with colistin treatment for at least 7 days between January 2014 and October 2017., Results: The mean age was 76.8 years, and mean Acute Physiology and Chronic Health Evaluation II score was 17.7. Eighteen (9.8%) and 128 (69.9%) patients had intravenous (IV) colistin alone and inhaled (IH) colistin alone, respectively. Thirty-seven patients had both IV and IH colistin, including 5 (2.7%) with concurrent, and 32 (17.5%) with non-concurrent use of IV and IH colistin. The 30-day mortality rate was 19.1% and 131 (71.6%) patients had clinical response. In the 175 patients with available data, 126 (72%) had microbiological eradication. The multivariate analyses revealed that IH colistin alone was an independent predictor for 30-day survival, clinical response, and microbiological eradication, and IV colistin alone was an independent predictor for clinical failure. Patients with IV colistin alone had a significantly higher nephrotoxicity rate than IH colistin alone (37.5% vs 6.1%, P = 0.001). Sub-group analysis of 52 patients with IV colistin for ≧ 4 days revealed that 14 (26.9%) patients had inappropriate dose, and inappropriate dose was an independent predictor for 30-day mortality., Conclusions: IH colistin provided good outcomes with few side effects, and appropriate dosing of IV colistin was important to avoid excess mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. No funding sources had any role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript., (Copyright © 2019. Published by Elsevier B.V.)

Long chain unsaturated fatty acids (LCUFAs) are emerging as critical contributors to inflammation and its resolution. Sensitive and accurate measurement of LCUFAs in biological samples is thus of great value in disease diagnosis and prognosis. In this work, a fluorous-derivatization approach for UPLC-MS/MS quantification of LCUFAs was developed by employing a pair of fluorous reagents, namely 3-(perfluorooctyl)-propylamine (PFPA) and 2-(perfluorooctyl)-ethylamine (PFEA). With this method, the LCUFAs in biological samples were perfluoroalkylated with PFPA and specifically retained on a fluorous-phase LC column, which largely reduced matrix interferences-induced quantitation deviation. Moreover, PFEA-labeled LCUFAs standards were introduced as one-to-one internal standards to farthest ensure unbiased results. Application of the proposed method enabled a reliable determination of eight typical LCUFAs with high sensitivity (LLOQ ranged from 30 amol to 6.25 fmol) and low matrix interferences (almost less than 10%). Such a high sensitivity could facilitate the determination of small-volume and low-concentration bio-samples. Further metabolic characterization of these targeted LCUFAs was monitored in OVA-induce asthma mice, requiring only 5 μL serum sample. Our results showed that asthmatic attack led to significant disturbances not only in the concentrations but also in the ratio among these LCUFAs. In view of the favorable advantages in sensitivity and accuracy, the present fluorous-paired derivatization approach will be expected to serve as a new avenue for dissecting the physiological and clinical implications of LCUFAs, thereby shedding light on the management of diseases related to their disturbances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Risk stratification for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may help clinicians choose appropriate treatments and improve the quality of care., Methods: A total of 695 patients hospitalized with AECOPD from January 2015 to December 2017 were considered. They were assigned to a death and a survival cohort. The independent prognostic factors were determined by multivariate logistic regression analysis. Meanwhile, we also compared the new scale with three other scores and tested the new scale internally and externally., Results: A new risk score was created, made up of six independent variables: age, D-dimer, albumin, cardiac troponin I, partial pressure of carbon dioxide and oxygenation index. The area under the receiver operator characteristic curve (AUROC) for the model was 0.929, and the other three CURB-65, DECAF and BAP-65 models were 0.718, 0.922 and 0.708. The Cohen's kappa coefficient between the new scale and DECAF was calculated to be 0.648, suggesting that there is a substantial consistency between the two. In the internal and external validation cohorts, 490 and 500 patients were recruited with a total mortality rate of 5.15%. The AUROC for in-hospital mortality was 0.937 in the internal cohort and 0.914 in external cohort, which was significantly better than the scores for CURB-65 and BAP-65, but it was not significantly different from the DECAF., Conclusions: The new scale may help to stratify the risk of in-hospital mortality of AECOPD. The DECAF performed as well as the new instrument, and it appears to be valid in Chinese patients., (© 2020 John Wiley & Sons Ltd.)

Background: Venous thromboembolism is a common vascular syndrome presenting as deep vein thrombosis and/or pulmonary embolism. Thrombus has the possibility of migrating into the left circulation via patent foramen ovale in certain extreme circumstances. Thrombus straddling a patent foramen ovale is a direct evidence of this scenario. However, the confirmed cases of thrombus in transit are still rare., Case Summary: A 32-year-old man suffered from recurrent syncope and intermittent dyspnea for 1 wk. Transthoracic echocardiography confirmed a thrombus straddling the patent foramen ovale, and thrombi were also found in the bilateral pulmonary artery by computed tomography. The man underwent inferior vena cava filter placement and thrombolysis with alteplase. Echocardiography showed the absence of thrombi in both the right atrium and left atrium 2 d after hospitalization. The man was discharged to home on warfarin without any complications 2 wk later., Conclusion: Scrutinizing intracardiac thrombi provides measurable value in pulmonary embolism as closure of patent foramen ovale may be considered in certain patients. Early intervention plays a critical role in thrombus straddling a patent foramen ovale. A sedentary lifestyle may predispose young adults to thromboembolism, even if there are no other risk factors., Competing Interests: Conflict-of-interest statement: Nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Gestational diabetes mellitus (GDM) causes oxidative stress in mothers and infants and causes vascular endothelial dysfunction, which is a key factor for maternal and fetal cardiovascular diseases in the later stage of GDM, seriously threatening the life and health of mothers and infants. Nowadays, metformin (MET) has been discovered to improve endothelial function, but studies regarding the mechanism of MET improving endothelial cell function and alleviating endothelial function under hyperglycemia are still extremely limited. We aimed to investigate whether MET exerts its protective role against hyperglycemia-induced endothelial dysfunction through p65 and Nrf2. In our studies, applying cell migration assay and tube formation assay, we observed an obvious improvement of endothelial function under MET-treated, as characterized by that MET accelerated GDM-attenuated migration and angiogenesis of HUVECs. And ELISA assay results uncovered that Nrf2 expression level was decreased in GDM placenta, HVUECs and maternal serum comparing with normal group, however activation Nrf2 largely ameliorated tube formation under hyperglycemic condition. Furthermore, MET elevated the Nrf2 expression level and the level of nuclear Nrf2 accumulation in hyperglycemic HUVECs. Besides, preliminary evidence predicted that Nrf2 expression was modulated by transcription factor p65, which was increased in GDM peripheral blood, placenta and HUVECs, and suppression of p65 could recover GDM-induced suppression of angiogenesis. In addition, we also confirmed MET restores the GDM-induced angiogenesis impairment may via downregulation of p65 and upregulation of Nrf2. Taken together, the endothelial protective effect of MET under GDM (HG) conditions could be partly attributed to its role in downregulating p65 and upregulating Nrf2., (Copyright © 2020 Sun, Lai, Wang, Xu, Li, Wang, Zheng and Zheng.)

Objective: To identify Parkinson's disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD., Methods: Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein-protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort., Results: A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine-cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA , GP6 , ITGB5 , and P2RY12 were independent risk factors of PD., Conclusion: Genes such as GP1BA , GP6 , P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine-cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.

The use of colloidal self-assembly to form the complex multiscale patterns in many optoelectronic devices has been a long-standing dream of the nanoscience community. While great progress has been made using charged colloids in polar solvents, controlled assembly from nonpolar solvents is much more challenging. The major challenge is colloidal clustering caused by strong van der Waals (vdW) attraction between long-chain surface capping ligands passivating the surface of nanocrystals. Such clustering degrades ordering in packing during the self-assembly process. While ligand exchange to provide colloidal stability in polar phases is often an option, this is not the case for the exciting new class of halide perovskites due to the material's solubility in essentially all polar solvents. Here, we report surface-functionalized self-assembly of luminescent CsPbBr 3 perovskite nanocubes by partially replacing long-chain oleyl groups (18 carbon chain) with short-chain thiocyanate (SCN - ). This enables the fabrication of ultrasmooth monolayer thin films of nanocubes with a root-mean-square (RMS) roughness of around 4 Å. This ultrasmooth large area self-assembled layer could act as high-efficiency optoelectronic devices like solar cells, light-emitting diodes (LEDs), transistors, etc. We correlate our experimental results with simulations, providing detailed predictions for lattice constants with chain conformations showing reduced free energy for cubes grafted with short-chain thiocyanate compared to long-chain oleyl groups, thus facilitating better self-assembly.

In this study, 127 light-duty gasoline cars and 10 light-duty gasoline trucks with different emission standards were selected to explore the influences of different conditions and vehicle parameters on the emission characteristics of carbon dioxide (CO 2 ), carbon monoxide (CO), nitrogen oxides (NO x ), hydrocarbons (HC), and methane (CH 4 ) using a portable emission measurement system based on a chassis dynamometer under acceleration simulation mode. The results showed that the gaseous pollutants of light-duty gasoline vehicles displayed a relatively lower emission rate under the idle condition, which accounted for only 22.9% and 25.8% of the emission rate at the accelerated condition and constant speed condition, respectively. The pollutant emission characteristics were closely related to the working conditions. The emission rates of CO 2 and NO x in the accelerated condition were less than those at the constant speed condition, while the emission rates of CO, HC, and CH 4 in the accelerated condition were higher than those at the constant speed condition. In the constant low-speed condition, the emission factors of CO 2 , CO, NO x , HC, and CH 4 were 383.20, 2.98, 1.60, 0.14, and 0.03 g·km -1 for light-duty gasoline cars, respectively, and 360.66, 2.64, 1.61, 0.0055, and 0.0027 g·km -1 for light-duty gasoline trucks, respectively. Tighter emission standards have caused significant reductions in emissions. The emission factors of CO, NO x , HC, and CH 4 could be decreased by 87.5%, 97.3%, 97.9%, and 86.4%, respectively, from China Ⅰ to China Ⅴ. A non-linear relationship was found between the age, odometer, vehicle weight, and vehicular emissions. In addition, the engine displacement was positively correlated with vehicular emissions.

In spite of the attractive potential application of the dynamic behavior and defect of metal-organic framework (MOF), the achievement of these features is a challenging goal in the MOF research field. Herein, we report a Co(II) MOF, namely, [Co 3 (L) 2 (4-PTZ) 2 (H 2 O) 2 ] n ·solvent (H 2 L = 5-(isonicotinamido)isophthalic acid, 4-PTZ = 5-(4-pyridyl)-1 H -tetrazole), that features dynamic structural transformation behaviors. By varying the coordination configuration of metal center through the removal of coordinated water molecules, the porous compound could undergo structural transformation to give a new crystalline phase with larger pore dimension. Moreover, the new phase features a mesoporous structure originating from the spatial defect that formed with the transformation process, which indicates that the modulation of dynamic behavior of the MOF could be a potential method for the engineering of a spatial defect. In addition, the gas sorption investigation results reveal that the new phase has enhanced selectivity for CO 2 /N 2 , CO 2 /CH 4 , and C 2 H 2 /C 2 H 4 systems compared with that of the pristine phase, suggesting the potential of spatial defect engineering for the tuning of MOF gas sorption properties.

Purpose: To investigate the value of ultrasound (US) and clinicopathological features of papillary thyroid cancer (PTC) in predicting Telomerase Reverse Transcriptase (TERT) promoter mutations., Methods: Preoperative US images of 351 surgically confirmed PTCs were evaluated in terms of PTCs size and US features. The basic clinicopathological features were also retrieved. Univariate and multivariate analyses were performed to identify the risk factors for TERT promoter mutations. A scoring system was developed based on the cumulative number of risk factors. The area under the receiver operating characteristic curve (AUC) and cut-off value were calculated to evaluate the diagnostic performance of the scoring system for predicting TERT promoter mutations., Results: TERT promoter mutations were found in 4.84% (17/351) of patients with PTCs. Patient age >50 years (OR: 6.244, P = 0.006), multifocality (OR: 21.071, P = 0.022), taller-than-wide shape (OR: 4.934, P = 0.029), microlobulated margin (OR: 4786, P = 0.032), and capsule contact or involvement (OR: 4.668, P = 0.030) were independent risk factors for TERT promoter mutations. TERT promoter mutations were relevant to more suspicious US and clinicopathological features than TERT promoter wild-type PTC (median, 4 vs. 1, P < 0.001). The cut-off value was 2.5 and the associated AUC was 0.908 (P < 0.001)., Conclusions: The probability of TERT promoter mutations increases along with the suspicious US features and clinicopathological characteristics, which may help to recognize patients who deserve a different approach, in terms of management and follow-up, in view of the worst outcome associated to this mutation.

Objective: We aimed to investigate practices of nasogastric tube (NGT) intubation and feeding for adults by clinical nurses in China., Methods: A self-designed and validated questionnaire comprising 30 questions was distributed to 560 clinical nurses in three comprehensive hospitals of Xiamen, China. The questionnaire covered participants' demographic characteristics, NGT placement, administration of enteral nutrition (EN), and monitoring or management of feeding intolerance., Results: A total 464 (82.9%) questionnaires were completed; 36.2% of nurses used nose-ear-xiphoid and 79.5% forehead-xiphoid measurement to define the internal length of the NGT. Many participants still used traditional methods to confirm NGT placement (auscultation of injected air 50.2%, bubble test 34.7% and observing feeding tube aspirate 34.3%). Bolus feeding was the most commonly used technique to administer EN. A total 97.0% of all nurses used syringes to measure gastric residual volume (GRV), and 62.7% measured GRV every 4-8 hours. The most frequently used GRV threshold values were 200 mL (44.6%) and 150 mL (25.2%). Most nurses stopped feeding immediately when encountering high GRV (84.3%) or diarrhea (45.0%). The nasogastric feeding practices of many clinical nurses were not consistent with international guidelines., Conclusions: Our study can provide an impetus for nursing administrators to revise their nasogastric feeding procedures, to promote compliance with evidence-based guidelines.

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in Angelica sinensis , ligustilide, has been reported to have the protective effect on AD. Whether ligustilide could protect against age-induced dementia is still unknown. In this study, we used an aging model, SAMP8 mice to investigate the neuroprotective effect of ligustilide. The behavioral tests (Morris water maze, object recognition task, open field test and elevated plus maze) results showed that ligustilide could improve the memory deficit in SAMP8 mice. For mechanism study, we found that the protein level of P-Drp1 (fission) was decreased and the levels of Mfn1 and Mfn2 (fusion) were increased after ligustilide treatment in animals and cells. Ligustilide increased P-AMPK and ATP levels. Malondialdehyde and superoxide dismutase activity results indicated that ligustilide exerts antioxidant effects by reducing the level of oxidative stress markers. In addition, ligustilide improved neural function and alieved apoptosis and neuroinflammation. These findings have shown that ligustilide treatment improves mitochondrial function in SAMP8 mice, and improves memory loss.

Physical medicine and rehabilitation (PM&R) is a specialty of medicine focused on optimizing function and quality of life for individuals with physical impairments, injuries, or disabling illnesses. Given the sometimes acute nature of the loss of function and even loss of independence, there are significant palliative care (PC) needs within patients seen by PM&R. This article, written by a team of PM&R and PC specialists, aims to help the PC team better understand the world of postacute care, expand their toolkit for treating musculoskeletal and neurological symptoms, improve prognostication for patients with brain and spinal cord injuries, and decide when patients may benefit from PM&R consultation and support. There is significant overlap between the populations treated by PM&R and PC. Better integration between these specialties will help patients to maintain independence as well as advance excellent patient-centered care.

Background: There has recently been an emphasis on improving cancer care globally, including access to lifesaving treatment and earlier identification of disease. This will lead to more survivors stricken by impairments related to the early and late effects of cancer treatment. An unintended consequence of the noble plan to improve oncology care worldwide is demand on health care systems that may be unable to accommodate increased patient care needs for myriad reasons. As a result, those with disabilities may suffer. Methods: Literature search and input from experts in the field were used to evaluate the growing need for cancer rehabilitation and survivorship care to reduce morbidity associated with cancer treatment. Results: Many governmental and non-governmental organizations have started initiatives to improve cancer care across the continuum, and reduce the symptom burden of those living with cancer. While the start is promising, many barriers must be overcome to ensure high-quality care that would reduce cost and improve patient access, including a lack of trained rehabilitation specialists, poor coordination of efforts, and funding restrictions. Furthermore, global efforts to improve rehabilitation care often do not emphasize cancer rehabilitation, potentially leaving a gap and increasing physical and economic costs of disability. Finally, low-resource countries face unique challenges in improving cancer rehabilitation care. Conclusion: Cancer rehabilitation and survivorship care are needed to improve health care quality, as there is an expected influx of cancer patients with new global efforts to improve oncology care. To accomplish this, rehabilitation initiatives must emphasize cancer rehabilitation as a component of any program, and oncology endeavors should include a plan for the rehabilitation of cancer survivors to reduce morbidity and health care cost.Implications for RehabilitationCancer rehabilitation has the potential to reduce morbidity and health care costs associated with cancer and disability worldwideAdvocacy from international organizations regarding cancer rehabilitation is increasing, but has been disjointed and incompleteLow-resource countries in particular face several barriers to providing cancer rehabilitation and survivorship care.

Bay cities have abundant land-sea resources and higher environmental carrying capacity. The high density of population and industry surrounding the bay makes bay cities a type of ecologically fragile areas. With Quanzhou, a typical bay city, as an example, we simulated the land use and landscape pattern change in 2030 based on multiple data sources (land use data, meteorological site data, topographic data and statistical data) using Logistic-CA-Markov coupling model to set natural scenarios, planning scenarios and protection scenarios. Four key ecosystem service (ES) including water retention, soil conservation, carbon sequestration (NPP), food supply and their trade-offs were calculated and predicted. Under the three scenarios, the area of cultivated land and construction land in Quanzhou City would increase in 2030. Forest land, grassland and water area would be reduced in varying degrees. The fragmentation of land use would be serious. In comparison with 2015, except for soil conservation service, water retention, carbon sequestrtion and food supply of Quanzhou City would decline to varying degrees in 2030. Ecosystem service function in natural scenario would be more decreased, with the decline under the protection scenario being lower than the planning scenario. In the protection and planning scenarios, the synergy between water conservation and soil conservation, water conservation and carbon sequestrtion, soil conservation and carbon sequestrtion in 2030 would be enhanced and the trade-offs would be weakened.

To evaluate the feasibility and clinical value of three-dimensional ultrasound in evaluating ovarian function in perimenopausal women. In this prospective cohort study, 102 patients with clinically suspected perimenopause and 90 patients with menopause were enrolled. These patients were classified into three groups according to the level of follicle stimulating hormone (FSH) and estradiol (E2): menopause group, perimenopause group, and normal group. Perimenopause group: There were significant differences in volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in the ovaries after treatment. Cycle 1 > cycle 0 ( p  < .05) and cycle 3 cycle 0 ( p  < .05), and in FSH: cycle 3 < cycle 0 ( p  < .05). Three-dimensional ultrasound in ovarian quantitative measurement can objectively reflect the change in the ovarian function, predicting the effect of drug treatment, and provided an objective information for early intervention to menopausal.

Gut microbiota and their metabolites (short-chain fatty acids, SCFAs) are associated with the pathogenesis of rheumatoid arthritis (RA). Total Clematis triterpenoid saponins (CTSs) prepared from Clematis mandshurica Rupr. possess therapeutic benefits for arthritic diseases. However, the poor pharmacokinetic properties of CTSs have obstructed the translation of these natural agents to drugs. Here, we examined the effects of CTSs on arthritis symptoms, gut microbiota and SCFAs in rats with collagen-induced arthritis (CIA). Our results showed that the arthritis index scores of CIA rats treated with CTSs were significantly lower than those of the model group. Most importantly, CTSs moderated gut microbial dysbiosis and significantly downregulated the total SCFA concentration in CIA rats. Compared to the control group, CTSs treatment have no significant side effects on the gut microbiota and SCFA metabolism in normal rats. Two differential analyses (LEfSe and DESeq2) were combined to study the details of the changes in gut microbiome, and twenty-four marker taxa at the genus level were identified via a comparison among control, model and CIA rats treated with high doses of CTSs. In particular, the mostly significantly increased gram-negative (G - ) and decreased gram-positive (G + ) genera in CIA rats were well restored by CTSs. The observed SCFA concentrations demonstrated that CTSs tend to maintain the balance of the gut microbiota. The data presented herein suggest that CTSs could ameliorate arthritis-associated gut microbial dysbiosis and may be potential adjuvant drugs that could provide relief from the gastrointestinal damage caused as a side effect of commonly used drugs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Turmeric (Curcuma longa L, Zingiberaceae) rhizomes exhibit versatile biological activities including the significant anti-cancer property. As an herbal medicine, the therapeutic effects of turmeric may be expressed by multi-components which have complicated integration effects on multi-targets. Therefore, having previously found three A549 cell-binding curcuminoids (curcumin, Cur; demethoxycurcumin, DMcur; bisdemethoxycurcumin, BMcur) from turmeric, studies were undertaken in this paper to determine the anti-cancer mechanism and integration effects of these curcuminoids by using chemical markers' knockout and UHPLC-LTQ Orbitrap MS-based metabolomics. Four curcuminoid-containing fractions including a mixture of 3 cell-binding curcuminoids (CE), and three individual curcuminoids with natural proportion in turmeric were prepared by chemical markers' knockout method. CE, Cur, DMcur and BMcur fractions showed significant anti-cancer activity on A549 cells. The activities of CE, Cur and BMcur fractions were comparative with the turmeric crude extract (TcE). In the metabolomics study, CE and three individual curcuminoid fractions changed the expression of 25 metabolites in A549 cells, which were involved in glycerophospholipid catabolism, sphingolipid metabolism and fatty acid metabolism, etc. Among them, glycerophospholipid catabolism was disordered greatly in CE group, while sphingolipid metabolism was suggested to be closely related to DMcur and BMcur activity. Furthermore, the metabolomics data showed that three curcuminoids existed synergistic and antagonistic actions and the use of multi-curcuminoids is more powerful than use of single curcuminoid on the metabolic alterations of A549 cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

With the rapid development of immunometabolism, 2-hydroxyglutarate (2-HG) is being promoted as a key immunometabolite to regulate the immune system. Based on the well-established crosstalk between 2-HG and other immunometabolites, here we firstly constructed a 2-HG metabolic panel by mapping the related metabolic pathways. Quantitative methods to globally monitor 2-HG metabolic panel are of great importance for immunometabolism study. However, the existence of enantiomer hampers the accurate measurement of these immunometabolites. This study addressed an original isotopically-paired chiral derivatization approach for UPLC-MS/MS quantification of 2-HG metabolic panel. To achieve better chromatographic separation, N-(p-toluenesulfonyl)-L-phenylalanyl chloride (TSPC) was utilized as an optical resolving reagent to form diastereomers. For accurate quantitation, an 18 O 2 -labeled-TSPC reagent was designed and readily synthesized to produce one-to-one internal standards. The developed approach enabled an accurate quantification of 13 immunometabolites in 2-HG metabolic panel with good linearity (R 2  > 0.99) and high sensitivity (0.5-120 fmol for LLOQ). With this method, we were able to simultaneously monitor the specific alterations of 2-HG metabolic panel in collagen-induced rheumatoid arthritis (CIA) rats. The measured levels of this panel ranged from 0.02 to 85.14 μg g -1 for synovium tissue and 0.012 to 87.75 μmol L -1 for serum samples. We envisage that the present isotopically-paired chiral derivatization approach will be practicable for different bio-samples to quantitatively profile the amino- and hydroxyl acids submetabolome, especially for the endogenous enantiomers. By virtue of the low cost of reagents and the simple procedure used in the assay, this method could be readily implemented., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Interplay between Cymbidium mosaic virus (CymMV)/Odontoglossum ringspot virus (ORSV) and its host plant Phalaenopsis equestris remain largely unknown, which led to deficiency of effective measures to control disease of P. equestris caused by infecting viruses. In this study, for the first time, we characterized viral small interfering RNAs (vsiRNAs) profiles in P. equestris co-infected with CymMV and ORSV through small RNA sequencing technology. CymMV and ORSV small interfering RNAs (siRNAs) demonstrated several general and specific/new characteristics. vsiRNAs, with A/U bias at the first nucleotide, were predominantly 21-nt long and they were derived predominantly (90%) from viral positive-strand RNA. 21-nt siRNA duplexes with 0-nt overhangs were the most abundant 21-nt duplexes, followed by 2-nt overhangs and then 1-nt overhangs 21-nt duplexes in infected P. equestris . Continuous but heterogeneous distribution and secondary structures prediction implied that vsiRNAs originate predominantly by direct Dicer-like enzymes cleavage of imperfect duplexes in the most folded regions of the positive strand of both viruses RNA molecular. Furthermore, we totally predicted 54 target genes by vsiRNAs with psRNATarget server, including disease/stress response-related genes, RNA interference core components, cytoskeleton-related genes, photosynthesis or energy supply related genes. Gene Ontology classification showed that a majority of the predicted targets were related to cellular components and cellular processes and performed a certain function. All target genes were down-regulated with different degree by vsiRNAs as shown by real-time reverse transcription polymerase chain reaction. Taken together, CymMV and ORSV siRNAs played important roles in interplay with P. equestris by down modulating the expression levels of endogenous genes in host plant., (© The Korean Society of Plant Pathology.)

Background: Common prosthetic options do not allow for enough independent control signals to control all the movements of the arm. Invasive approaches to obtain prosthetic control signals are being developed to provide people with upper limb loss improved prosthetic control and feedback., Objective/hypothesis: This study explored the prosthetic qualities that are important to users and examined the factors that play into the decision to consider invasive prosthetic interfaces that allow for enhanced prosthetic control., Methods: Individuals participated in semi-structured focus groups or in individual semi-structured interviews (N = 11). A semi-structured interview guide containing open-ended questions was used to learn about ideal prosthesis qualities and interest in prosthetic technology interfaces including targeted muscle reinnervation, peripheral nerve interface, and cortical interface. Qualitative content analysis with an inductive approach was used for transcript analysis., Results: Participants were most interested in improving the dexterity and durability of prosthetic options. Recovery time, anticipated risk, medical co-morbidities, and baseline functional status influenced willingness to consider invasive prosthetic interfaces. Participants were interested in learning more about all three invasive interfaces but had the most concerns about cortical interfaces., Conclusions: Attitudes toward invasive control interfaces vary. Further education on invasive control interfaces and additional conversations between prosthetic developers and people with limb loss will help to develop effective prosthetic devices that potential consumers will use., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microglia, the brain-resident macrophage, is known as the innate immune cell type in the central nervous system. Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development. Mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) frequently occur in gliomas, which leads to accumulation of oncometabolic product 2-hydroxyglutarate (2HG). Moreover, IDH1/2 mutations were found to correlate with better prognosis in glioma patients. In the present study, we investigated the effects of the 2HG on microglial inflammatory activation. We showed that the conditioned media (CM) from GL261 glioma cells stimulated the activation of BV-2 microglia cells, evidenced by markedly increased expression of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), CCL2 (C-C motif chemokine ligand 2) and CXCL10 (C-X-C motif chemokine 10). CM-induced expression of proinflammatory genes was significantly suppressed by pretreatment with a synthetic cell-permeable 2HG (1 mM) or a nuclear factor-κB (NF-κB) inhibitor BAY11-7082 (10 μM). In lipopolysaccharide (LPS)- or TNF-α-stimulated BV-2 microglia cells and primary microglia, pretreatment with 2HG (0.25-1 mM) dose-dependently suppressed the expression of proinflammatory genes. We further demonstrated that 2HG significantly suppressed LPS-induced phosphorylation of IκB kinase α/β (IKKα/β), IκBα and p65, IκB degradation, and nuclear translocation of p65 subunit of NF-κB, as well as NF-κB transcriptional activity. Similarly, ectopic expression of mutant isocitrate dehydrogenase 1 (IDH1) (R132H) significantly decreased TNF-α-induced activation of NF-κB signaling pathway. Finally, we revealed that activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and subsequent inhibition of mammalian target of rapamycin (mTOR) signaling contributed to the inhibitory effect of 2HG on NF-κB signaling pathway in BV-2 cells. Taken together, these results, for the first time, show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF-κB signaling pathway and provide evidence that oncometabolite 2HG may regulate glioma development via modulating microglial activation in tumor microenvironment.

Tinnitus, the perception of sound in the absence of external stimuli, is often a disturbing symptom for which the underlying functional neuroanatomy still remains poorly understood. Most studies have focused solely on functional connectivity changes in the auditory cortex of tinnitus patients. The aim of this study was to investigate whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of five resting-state networks comprising the auditory, the default mode, the external control left and right, and the salience network. For this purpose, a large sample of one hundred and thirty-five subjects underwent resting-state functional magnetic resonance imaging and their behavioural scores were obtained using clinical evaluations. Networks were extracted using independent component analysis, and functional connectivity patterns in the extracted networks were evaluated by a graph theoretical approach. The effects of tinnitus for each network were investigated by correlating the graph strength of all the regions with the tinnitus behavioural scores using stepwise fit regression analysis. Results indicated that alterations of functional interactions between key neural circuits of the brain are not limited to one single network. In particular, tinnitus distress showed a strong correlation with the connectivity pattern within and between the right executive control network and the other four resting-state networks, indicating that tinnitus distress is probably the consequence of a hyperactive attention condition. Among the behavioural scores, the strongest correlation was observed between age and hearing loss, while the tinnitus objective loudness was not correlated with any behavioural scores.

Background: The accurate evaluation of BRAF V600E mutation in preoperative fine-needle aspiration cytology (FNAC) specimens is important for making management decisions in thyroid nodules (TNs). The aim of this study was to assess the false-positive and false-negative BRAF V600E mutations in thyroid FNAC specimens and their influence on diagnosis of TN., Methods: This prospective study enrolled 292 nodules in 269 patients who underwent BRAF V600E mutation analysis using amplification refractory mutation system-quantitative real-time polymerase chain reaction (ARMS-qPCR) both in FNAC specimens and formalin-fixed, paraffin-embedded (FFPE) tissue samples after surgery. The false-positive and false-negative mutations for BRAF V600E analysis using ARMS-qPCR in FNAC specimens were recorded, with reference to the results of BRAF V600E mutation analysis using ARMS-qPCR in FFPE tissue sample. Diagnostic performances of FNAC, BRAF V600E mutation analysis in FNAC specimens, BRAF V600E mutation analysis in FFPE tissue sample, and the combination of FNAC and BRAF V600E mutation analysis for predicting thyroid malignancy were assessed., Results: The false-positive and false-negative mutations for BRAF V600E analysis using ARMS-qPCR in FNAC specimens were 10.1% (19/189) and 7.1% (7/98), respectively. FNAC combined with preoperative BRAF V600E mutation analysis significantly increased the diagnostic sensitivity from 75.7% to 92.3%, and accuracy from 78.7% to 90.6% in comparison with FNAC alone (both P < .001). No significant differences were found between the combination of FNAC and BRAF V600E mutation analysis in FNAC specimens and the combination of FNAC and BRAF V600E mutation analysis in FFPE tissue sample (sensitivity: 92.3% vs 91.9%; accuracy: 90.6% vs 91.3%; both P > .05)., Conclusions: FNAC combined with preoperative BRAF V600E mutation analysis can significantly increase the diagnostic performance in comparison with FNAC alone. False-positive and false-negative BRAF V600E mutation results are found in preoperative FNAC specimens, whereas it does not affect the overall auxiliary diagnosis of TNs., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Mitogen-activated protein kinase 6 (MKK6) is one of the major important central regulatory proteins response to environmental and physiological stimuli. In this study, a novel MKK6, EcMKK6, was isolated from Epinephelus coioides, an economically important cultured fish in China and Southeast Asian counties. The open reading frame (ORF) of EcMKK6 is 1077 bp encoding 358 amino acids. EcMKK6 contains a serine/threonine protein kinase (S&#95;TKc) domain, a tyrosine kinase catalytic domain, a conserved dual phosphorylation site in the SVAKT motif and a conserved DVD domain. By in situ hybridization (ISH) with Digoxigenin-labeled probe, EcMKK6 mainly located at the cytoplasm of cells, and a little appears in the nucleus. EcMKK6 mRNA can be detected in all eleven tissues examined, but the expression level is different in these tissues. After challenge with Vibrio alginolyticus and Singapore grouper iridovirus (SGIV), the transcription level of EcMKK6 was apparently up-regulated in the tissues examined. The data demonstrated that the sequence and the characters of EcMKK6 were conserved, EcMKK6 showed tissue-specific expression profiles in healthy grouper, and the expression was significantly varied after pathogen infection, indicating that EcMKK6 may play important roles in E. coioides during pathogen-caused inflammation., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Esophageal squamous cell carcinoma (ESCC) accounts for the highest incidence rate worldwide and is responsible for the fourth leading cause of cancer-related death. Currently, serologic biomarkers for early ESCC diagnosis are needed for timely treatment., Methods: The performance of a four-autoantibody panel (i.e., anti-TP53, HRAS, CTAG1A, and NSG1) was evaluated by ELISA for the early diagnosis of ESCC with 569 retrospective serum samples. A training set comprising 129 patients with early-stage ESCC, 130 patients with esophageal benign lesion (EBL), and 150 healthy controls (HC) was used to develop an early ESCC predictive model. Data obtained from an independent validation set were used to evaluate and validate the predictive model to distinguish the early ESCC from the controls (EBL+HC). Finally, a multiplexed assay based on the Luminex xMAP technology platform was developed to enable simultaneous detection of the four-autoantibody panel using the validation set., Results: The four-autoantibody panel significantly discriminated early ESCC cases from the controls with 62.8% sensitivity at 88.9% specificity in the training set and with 58.0% sensitivity at 90.0% specificity in the independent validation set. The results of the multiplexed assay using xMAP technology for early ESCC showed a significant correlation with that of the ELISA assays with 66.0% sensitivity at 90.9% specificity., Conclusions: A four-autoantibody panel showed good performance for early ESCC diagnosis with ELISA and could be further developed into a multiplex assay using the Luminex xMAP technology., Impact: The four-autoantibody panel could be used for serologic screening for early ESCC., (©2019 American Association for Cancer Research.)

Considerable attention has been drawn to the lead halide perovskites (LHPs) because of their outstanding optoelectronic characteristics. LHP nanosheets (NSs) grown from single crystalline lead halide possess advantages in device applications as they provide the possibility for control over morphology, composition, and crystallinity. Here, free-standing lead bromide (PbBr 2 ) single-crystalline NSs with sizes up to one centimeter are synthesized from solution. These NSs can be converted to LHP while maintaining the NS morphology. We demonstrate that these perovskite NSs can be processed directly for fabrication of photodetector and laser arrays on a large scale. This strategy will allow high-yield synthesis of large-size perovskite NSs for functional devices in an integrated photonics platform.

Liquid chromatography-mass spectrometry based profiling of microbial metabolites has been a challenging task due to their diverse physicochemical properties and wide concentration ranges. This study is aimed to develop a systematic platform for the broad-scale profiling of microbial metabolites by integrating aqueous-lipophilic biphasic extractions and chemical derivatizations with a data-dependent automatable metabolite annotation algorithm. This complementary strategy of detection will not only largely expand the metabolite coverage, but also facilitate the drawing out of interested submetabolome using designed chemical derivatizations. Then, the data-dependent metabolite annotation algorithm is able to automatically match the raw MS/MS data with those of compounds in the self-collected databases. The performance of this platform is illustrated through the analysis of two representative bacteria (Escherichia coli and Pseudomonas aeruginosa) and intestinal contents samples from experimental colitis mice. As a result, 292 metabolites corresponding to 875 annotated features distributing over 25 chemical families were putatively annotated in a short time. Of these metabolites, 197 and 218 are respectively from the bacteria and intestinal contents, and 107 are identified in all three biological samples. This systematic platform could be used to accomplete high-coverage detection and high-quality data processing of microbial metabolites. At the same time, chemical derivatization design and the establishment of self-collected databases will facilitate self-driven untargeted analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The objective of the present study was to observe and analyze the significance of perfusion-weighted imaging for guiding the operation implementation for non-enhanced glioma, and analyze the estimation of the histopathological grade of the non-enhanced glioma and the accuracy of the degree of malignancy degree before surgery., Methods: Fifty-six patients diagnosed with non-enhanced glioma through conventional magnetic resonance scanning were selected. Before surgery, conventional magnetic resonance scanning and perfusion-weighted imaging were performed on all patients. The property classification was performed with the perfusion-weighted imaging parameters: cerebral blood volume (CBV) and cerebral blood flow (CBF) before surgery., Results: Surgery was performed on the 56 patients. Tumors were excised and processed for histopathological classification and semi-quantitative immunohistochemical analysis of vascular endothelial growth factor (VEGF) levels. Histology was compared after surgery and the classification accuracy rate was analyzed before surgery. Additionally, conventional magnetic resonance scanning and perfusion-weighted imaging were performed on 15 patients during surgery. We compared and analyzed the reference value of perfusion-weighted imaging before and during surgery. Residual diseased tissues were excised; histopathological examination was performed, and semi-quantitative immunohistochemical analysis of VEGF was performed. Regarding maximal magnetic resonance perfusion-weighted imaging measured before surgery, the CBV, CBF, and expression level of VEGF were positively correlated with the pathological grade of tumors. If the CBV and CBF values of the non-enhanced glioma were higher, the grade of malignancy was higher (P<0.01), and the positive expression rate of VEGF was higher (P<0.01)., Conclusions: Magnetic resonance perfusion-weighted imaging can display vessel growth and distribution within non-enhanced gliomas before surgery, and effectively evaluate the histopathological grade and grade of malignancy, and provide accurate guidance for tumor resection during surgery.

Objective: To investigate the effect of SARI overexpression on the proliferation and apoptosis of core binding factor leukemia (CBFL) cells and explore the potential molecular mechanisms., Methods: C-KIT N822K mutation status in Kasumi-1 cell line was detected by exon 17 sequencing. Then the SARI lentiviral vector (pGC-FU-SARI) was constructed, meanwhile Kasumi-1 cells were transfected with the SARI lentiviral vector. Quantitative PCR and Western blot were employed to identify efficacy of SARI overexpression after the transfection of cells. Cells were divided into three groups, including the cells infected with pGC-FU-SARI (OE group), the cells infected with pGC-FU-GFP (NC group) and the untreated cells (blank control group). Cell proliferative activity was tested by MTT assay, cell apoptosis was measured by flow cytometry (FCM) and the expression of apoptosis-related proteins: BCL-2,BAX,Cyto C,Caspase 9,Caspase 3,cleaved-Caspase 3,PARP and cleaved-PARP as well as PI3K/Akt pathway proteins: PI3K（p85）,p-PI3K（p85）,Akt and p-Akt were detected by Western blot., Results: The Kasumi-1 cells were detected to bear c-KIT N822K (T>A) mutation. The Kasumi-1 cells with SARI was overexpression were construeted successfully. Compared with NC group, the cell proliferation was decreased and cell apoptosis was increased; BCL-2 expression was reduced, BAX expression was enharued; cyto C expression appeared; the expression of Caspase 9 and Caspase 3 was down-regulated, the expression of cleaved Caspase 3 was up-regulated; the PARP expression was decreased, cleaved PARP expression was increased; the phosphorylation level of PI3K/Akt pathway proteins: p-PI3K/PI3K, p-Akt/Akt was down-regulated in OE group (P<0.05)., Conclusion: SARI gene may suppress the proliferation of CBFL cells, and induce their apoptosis through the mitochondrial pathway, which may be related with the inhibition of PI3K/Akt pathway.

To evaluate the value of intraperitoneal hyperthermic perfusion (IPHP) in the treatment of gastric cancer.Gastric cancer (GC) is a malignancy with poor prognosis, recent years have demonstrated advances in the use of IPHP for the treatment of advanced gastric cancer (AGC), but the outcome is controversial.Between January 2015 and January 2017, 134 patients with GC were treated with IPHP in our surgery department, 130 of them were advanced GC patients, and other 1439 cases were treated without IPHP for comparison. In this retrospective cohort study, demographic, perioperative data, and follow-up data were analyzed by univariant analysis, Kaplan-Meier and Cox regression survival analysis.We found the 1-year survival in IPHP group was significantly longer than it in non-IPHP group (85.5% vs 73.8%, P = .027). and IPHP decreased mortality 1.8 times in 2-year course (OR = 0.556, P = .004). The incidence rate of total complications in IPHP group was similar to that in the Non-IPHP group (6.67% vs 7.46%, respectively; P = .718). We classified all patients into four groups, operation alone, operation + chemotherapy, operation + IPHP, and operation + IPHP + chemotherapy. The 1-year survival in the groups was 70.2%, 77.5%, 83.1%, and 93.5%, respectively (P = .001), compared with the group of operation alone, the 2-year mortality risk was decreased 1.76 times (OR = 0.569, P = .030) and 2.59 times (OR = 0.385, P = .022) in operation + IPHP group and operation + IPHP + chemotherapy group.Our results suggest that IPHP could contribute to improve survival of patients with gastric cancer. And the modality of operation + IPHP + chemotherapy is the optimal treatment modality for gastric cancer.

The phytohormone 6-benzylaminopurine (6-BAP) significantly improves lipid synthesis of oleaginous microorganisms with the great potential applied in lipid production. In the current study, the lipid and DHA productions in oleaginous Aurantiochytrium sp. were found to be improved by 48.7% and 55.3%, respectively, induced by 6-BAP treatments. Then, using high-throughput RNA-seq technology, the overall de novo assembly of the cDNA sequence data generated 53871 unigenes, and 15902 of these were annotated in at least one database. The comparative transcriptomic profiles of cells with and without 6-BAP treatments revealed that a total of 717 were differently expressed genes (DE), with 472 upregulated and 245 downregulated. Further annotation and categorization indicated that some DE genes were involved in pathways crucial to lipid and DHA productions, such as fatty acid synthesis, central carbon metabolism, transcriptional factor, signal transduction, and mevalonate pathway. A regulation mode of 6-BAP, in turn, perception and transduction of 6-BAP signal, transcription factor, expression regulations of the downstream genes, and metabolic changes, respectively, was put forward for the first time in the present study. This research illuminates the transcriptomic mechanism of phytohormone stimulation of lipid and DHA production in an oleaginous microorganism and provides the potential targets modified using genetic engineering for improving lipid and DHA productivity.

Pichia pastoris expression is a mature and efficient eukaryotic expression system. In this work, Aspergillus oryzae lipase (AOL, with the molecular mass of 28 kDa), which can perform highly stereoselective hydrolysis of (R, S)-methyl 2-(4-hydroxyphenoxy) propanoate, was expressed in P. pastoris X-33. The specific activity of AOL was 432 U/mg, which was obtained by fed-batch cultivation in a 5 L bioreactor using a methanol feeding strategy. After fermentation, the supernatant was concentrated by ultrafiltration with a 10 kDa cut-off membrane and purified with DEAE-Sepharose™ FF ion-exchange chromatography and phenyl Seflnose™ 6 FF hydrophobic interaction chromatography. The purified lipase activity reached 5509 U/mg. AOL showed high activity toward short-chain triacylglyceride (C 4 ), and the optimum temperature and pH were 40 °C and 8.0, respectively. The purified enzyme activity was inhibited by Zn 2+ and Cu 2+ . Moreover, the K m and V max values were 1 mM and 32.89 mmol/min, respectively., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aim: The dramatic color change after iodine staining (from white-yellow to pink after 2-3 min), designated as the "pink-color sign" (PCS), is indicative of esophageal high-grade intraepithelial neoplasia (HGIN) or an invasive lesion. However, no study has yet examined the association between the time of PCS appearance and histopathology. We investigated the association between the time of PCS appearance and esophageal histopathology in 456 lesions of 438 patients who were examined for suspected esophageal cancer., Materials and Methods:: The records of 495 consecutive patients who had suspected esophageal cancer based on gastroscopy and who underwent Lugol's chromoendoscopy from January 2015 to March 2018 were retrospectively reviewed. The time of PCS appearance was recorded in all patients, and tissue specimens were examined., Results: We examined 456 lesions in 438 patients. Use of PCS positivity at 2 min for the diagnosis of HGIN/invasive cancer had a sensitivity of 84.1%, a specificity of 72.7%, and an accuracy of 80.4%. We classified the PCS-positive patients in whom the time of PCS appearance was recorded (168 lesions) into 4 groups: 0-30, 31-60, 61-90, and 91-120 s. Based on a 60-s time for appearance of the PCS, the area under the receiver operating characteristic curve was 0.897, indicating good validity. At the optimal cutoff value of 60 s, the sensitivity was 90.2% and the specificity was 82.3%. The appearance of the PCS within 60 s had a diagnostic accordance rate of 88.6%, significantly higher than appearance of the PCS within 2 min (79.7%, P < 0.05)., Conclusion: Appearance of the PCS within 1 min after iodine staining has a higher diagnostic accordance rate for esophageal HGIN/invasive cancer than appearance of the PCS at 2 min., Competing Interests: None

Background: To analyze the cardio-protective effects of ticagrelor in patients with acute coronary syndrome with S-T segment elevation., Methods: The sample was 200 patients who had been diagnosed with acute coronary syndrome accompanied by diabetes Mellitus type II. Only patients having ST segment elevation before the treatment were included. Then, the subjects were further randomly divided into an observation group and a control group. The control group of 100 patients received clopidogrel; the observation group of 100 patients of ticagrelor. The serous creatine kinase CK-MB, functional cardiac indexes of left ventricular end diastolic diameter (LVDD), cardiac troponin I, ventricular ejection fraction, and relevant major adverse cardiovascular events (MACE) were compared between the two groups., Results: One month after a percutaneous coronary intervention (PCI) the observation group showed better results against angina, stent thrombosis, and all-cause mortality compared with those of the control subjects. Six months after treatment, both groups suffered adverse reactions. The number of patients who suffered adverse reactions in respiratory tract in the observation group was higher than in the control group. The inhibition of platelet aggregation IPA of ticagrelor was found to be significantly higher than clopidogrel, having a significant p value., Conclusion: Ticagrelor can effectively protect myocardial function for patients with ST-segment elevation acute coronary syndrome accompanied by diabetes and can reduce the incidence of adverse reactions.., Competing Interests: Conflict of interest Conflict of interest statement: Authors state no conflict of interest.

Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer's disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors. Then, we stereotaxically injected EphB2-Flox-AAV into the hippocampus of GFAP-cre/APP/PS1 mice and further evaluated hippocampal synaptic plasticity and astroglial function. Interestingly, astrocytic EphB2 expression was significantly increased in APP/PS1 mice in contrast to its expression profile in neurons. Moreover, depressing this astroglial EphB2 upregulation enhanced hippocampal synaptic plasticity, which results from harmful D-serine release. These results provide evidence of the different expression profiles and function of EphB2 between astrocytes and neurons in AD pathology., Competing Interests: None.

Ginsenoside Rb1 (Rb1), as the major bioactive ingredient of Panax ginseng C.A. Meyer, elicited a novel antidepressant-like effect in the forced swim test (FST) in chronic unpredictable mild stress (CUMS) rats in our previous study. To further explore the molecular mechanism of Rb1 on the neurotransmitters such as 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), norepinephrine (NE), dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), glutamate (Glu) and gamma-aminobutyric acid (GABA) in this antidepressant-like effect, the neurochemical changes in the monoaminergic and aminoacidergic receptors were investigated in the present pharmacological study by using reuptake inhibitors, receptors agonists and antagonists. The results showed that a sub-effective dose of Rb1 (5 mg/kg, p.o.) co-administered with fluoxetine (1 mg/kg, i.p., a selective serotonin reuptake inhibitor), reboxetine (2.5 mg/kg, i.p., a noradrenalin reuptake inhibitor), bupropion (10 mg/kg, i.p., a dopaminergic reuptake inhibitor), Mk-801 (0.05 mg/kg, i.p., an N-methyl-d-aspartic acid (NMDA) receptor antagonist) or baclofen (0.1 mg/kg, i.p., a selective GABA agonist) significantly decreased the immobility time in the FST. In addition, pretreating mice with NAN190 (0.5 mg/kg, i.p., a 5-HT 1A receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT 2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT 3A receptor antagonist), prazosin (1 mg/kg, i.p., an α 1 -adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α 2 -adrenoceptor antagonist), SCH23390 (0.05 mg/kg, i.p., a selective D 1 receptor antagonist), haloperidol (0.2 mg/kg, i.p., a non-selective D 2 receptor antagonist), NMDA (75 mg/kg, i.p., an agonist at the glutamate site) or bicuculline (4 mg/kg, i.p., a competitive GABA antagonist) reversed the antidepressant-like effect of Rb1 (10 mg/kg, p.o.) in the FST. The results obtained for the neurotransmitters in the mouse hippocampus (CA3) and prefrontal cortex showed that Rb1 up-regulated the levels of 5-HT, 5-HIAA, NE, DA, and GABA and decreased the level of Glu. However, there were no significant differences in HVA or DOPAC. Furthermore, there were no significant alterations in the total path of spontaneous locomotor activity in all treatments. These results suggest that both monoaminergic (serotonergic, noradrenergic and dopaminergic) and aminoacidergic (glutamatergic and GABAergic) receptors may be involved in the antidepressant-like effect of Rb1., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Two isostructural lanthanide-based MOFs [Ln(HL)L]·H2O (1-Ln, Ln = Eu, Dy, H2L = 5-((pyridin-4-ylthio)methyl)isophthalic acid) were successfully obtained via the solvothermal reaction. 1-Eu exhibits high fluorescence quenching efficiency for C2O72- and Fe3+, which can be potentially used as a luminescent probe; 1-Dy behaves as a typical single-molecule magnet with an energy barrier (ΔUeff) of 54(2) K.

Background and Purpose: In response to hypoxic succinate accumulates in arthritis synovium, however, the implication is little known. This study aims to investigate whether succinate could act as a metabolic signal linking metabolic alternation with angiogenesis in arthritis synovium., Experimental Approach: The interaction between elevated succinate and VEGF production was examined in endothelial cells. Succinate production, HIF-1α induction and angiogenesis in the hypoxic synovium of collagen-induced arthritis rats were also investigated., Key Results: Intracellular succinate promoted VEGF production and induced angiogenic response dependent on HIF-1α induction in endothelial cells. Luciferase reporter assay showed that succinate increased VEGF expression through gene promoter activation dependent on HIF-1α induction. Intracellular succinate released into intercellular space, where extracellular succinate activated succinate receptor G-protein-coupled receptor 91 (GPR91) and induced VEGF production, further exacerbating angiogenesis. In addition, TGF-β1 treatment increased succinate production due to the reversal of succinate dehydrogenase (SDH) activation, and consistently, SDH inhibitor dimethyl malonate reduced angiogenesis in the arthritis synovium., Conclusion and Implications: More than an intermediate, succinate functioned as a signaling molecule to link metabolic reprograming with angiogenesis. Intracellular succinate induced angiogenesis through HIF-1α induction, while extracellular succinate acted on GPR91 activation, working together to disturb energy metabolism and exacerbate inflammation and angiogenesis in arthritis synovium. Our work suggested that suppression of SDH could prevent succinate accumulation and inhibit angiogenesis via blocking HIF-1α/VEGF axis. This finding not only provides a novel insight into angiogenesis, but also reveals a potential therapeutical strategy to attenuate revascularization in arthritis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To achieve a feasible heat-assisted magnetic recording (HAMR) system, a near-field transducer (NFT) is necessary to strongly focus the optical field to a lateral region measuring tens of nanometres in size. An NFT must deliver sufficient power to the recording medium as well as maintain its structural integrity. The self-heating problem in the NFT causes materials failure that leads to the degradation of the hard disk drive performance. The literature reports NFT structures with physical sizes well below 1 micron which were found to be thermo-mechanically unstable at an elevated temperature. In this paper, we demonstrate an adiabatic NFT to address the central challenge of thermal engineering for a HAMR system. The NFT is formed by an isosceles triangular gold taper plasmonic waveguide with a length of 6 µm and a height of 50 nm. Our study shows that in the full optically and thermally optimized system, the NFT efficiently extracts the incident light from the waveguide core and can improve the shape of the heating source profile for data recording. The most important insight of the thermal performance is that the recording medium can be heated up to 866 K with an input power of 8.5 mW which is above the Curie temperature of the FePt film while maintaining the temperature in the NFT at 390 K without a heat spreader. A very good thermal efficiency of 5.91 is achieved also. The proposed structure is easily fabricated and can potentially reduce the NFT deformation at a high recording temperature making it suitable for practical HAMR application.

CD58 and CD2 have long been known as a pair of reciprocal adhesion molecules involved in the immune modulations of CD8 + T and NK-mediated cellular immunity in humans and several other mammals. However, the functional roles of CD58 and CD2 in CD4 + T-mediated adaptive humoral immunity remain poorly defined. Moreover, the current functional observations of CD58 and CD2 were mainly acquired from in vitro assays, and in vivo investigation is greatly limited due to the absence of a Cd58 homology in murine models. In this study, we identified cd58 and cd2 homologs from the model species zebrafish ( Danio rerio ). These two molecules share conserved structural features to their mammalian counterparts. Functionally, cd58 and cd2 were significantly upregulated on antigen-presenting cells and Cd4 + T cells upon antigen stimulation. Blockade or knockdown of Cd58 and Cd2 dramatically impaired the activation of antigen-specific Cd4 + T and mIgM + B cells, followed by the inhibition of antibody production and host defense against bacterial infections. These results indicate that CD58/CD2 interaction was required for the full activation of CD4 + T-mediated adaptive humoral immunity. The interaction of Cd58 with Cd2 was confirmed by co-immunoprecipitation and functional competitive assays by introducing a soluble Cd2 protein. This study highlights a new costimulatory mechanism underlying the regulatory network of adaptive immunity and makes zebrafish an attractive model organism for the investigation of CD58/CD2-mediated immunology and disorders. It also provides a cross-species understanding of the evolutionary history of costimulatory signals from fish to mammals as a whole.

Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model. We found that treatment with 25nmol/kg. i.p. once-daily after the induction of SE for 7 days reduced chronic inflammation as shown by reduced numbers of activated microglia and astrocytes, and reduced levels of TNF-α and IL-1ß in the hippocampus. The mitochondrial stress marker BAX was reduced and the survival factor Bcl-2 was enhanced by liraglutide. Blood glucose levels were not affected by liraglutide. We show for the first time that liraglutide can reduce the chronic inflammation and mitochondrial stress induced by SE, and the results suggest that GLP-1 receptor agonists such as liraglutide have restorative and protective effects in the brain after SE and could serve as a potential treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Terphenyllin (1), a naturally abundant p-terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2-5. To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α-glucosidase inhibitory, cytotoxic, and antibacterial activities. Compounds 1, 3, 4, 7, 8, 10, 11, 14, 15, 21, 23, 24, 29, 39, and 40 showed significant α-glucosidase inhibitory activity with IC 50 values of 4.79-15 μM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC 50  = 192.0 μM) and acarbose (IC 50  = 707.9 μM). Compounds 7 and 10 have relatively higher therapeutic indices (CC 50 /IC 50  = 17 and 10, respectively), representing potential promising leads. The enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α-glucosidase with Ki values of 1.50 and 3.45 μM, respectively. Additionally, compounds 14, 21, 26, 29, 32, 35, and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC 50 values ranging from 0.15 to 5.26 μM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Superoxide anion (O 2 .- ), as the first generated reactive oxygen species (ROS), has been considered to be highly deleterious to cell functions. The measurement of intracellular O 2 .- level is of great importance to uncover its roles in a variety of oxidative damage diseases. Hydroethidium (HE) fluorescence-based method is dominating intracellular O 2 .- assay by monitoring the unique product 2-OH-E + of HE/O 2 .- reaction. However, the avoid-less cross-interference of red fluorescence limited its ability to provide trustworthy information on intracellular O 2 .- formation. By the detection of 2-OH-E + , we herein developed and validated an improved LC/MS-based method for the measurement of intracellular O 2 .- . Firstly, we demonstrated the proportionality of HE/O 2 .- reaction. Secondly, ungerimine was used as internal standard to eliminate daily basis and matrix effect in the LC/MS-based detection of 2-OH-E + . Afterward, the total protein concentration was utilized for cell number normalization. Accordingly, an equation was further proposed to calculate the relative abundance (RA) of intracellular O 2 .- . Finally, the developed method has been successfully utilized to evaluate the inhibitory effects of natural compounds on O 2 .- generation, the result of which was validated by the HE-based fluorescent measurement. Compared with the fluorescent measurement, the LC/MS-based intracellular O 2 .- assay method is more sensitive, selective and accurate., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Kruppel like factor 6 (KLF6), a member of KLF family, which has classic zinc finger structure, is broadly considered to have anticancer activity. The role of SV2 variant, one of KLF6 alternative splicing isoforms has not yet been definite in the colorectal cancer. This study aimed to detect the expression of the KLF6-SV2 in colorectal cancer and investigate its impact on cell proliferation and apoptosis. qRT-PCR was used to quantitatively determine KLF6-SV2 mRNA expression in colorectal cancer samples, corresponding normal tissue, normal colonic mucosal cell line FHC and seven colorectal cancer cell lines. SW480 and SW620 cell models with over-expressing KLF6-SV2 were constructed. Cell proliferation, cell cycle and apoptosis were measured respectively using MTT assay, DNA ploidy detection and Annexin V flow cytometry. Meanwhile, expression of p53, p21 and Bax were detected by qRT-PCR and western blot. The mRNA expression level of KLF6-SV2 in colorectal cancer tissues (0.783±0.409) was decreased than in corresponding normal tissues (1.086±0.449) (P<0.01), and expression in SW480 and SW620 were lower than in FHC, HCT116, LoVo, HT29, Caco-2 and RKO. In cell lines over-expressing KLF6-SV2, cell proliferation was markedly suppressed, cell cycle was blocked and cell apoptosis was significantly induced. Simultaneously, expression of p21 and Bax were remarkably up-regulated, while p53 remained unchanged. Decreased expression of KLF6-SV2 may be associated with the occurrence and development of colorectal cancer. KLF6-SV2 plays a role as tumor suppressor by efficiently blocking cell proliferation, arresting cell cycle and inducing apoptosis in colorectal cancer, which may be related to increased expression of p21 and Bax.