Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated with porin OmpK36 loss and DHA-1 β-lactamase production

Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains are being increased worldwide. Five pan-resistant K. pneumoniae strains have been isolated from respiratory and ICU wards in a Chinese hospital, and reveal strong resistance to all β-lactams, fluoroquinolones and aminoglycosides. Totally 27 β-lactamase genes and 2 membrane pore protein (porin) genes in 5 K. pneumoniae strains were screened by polymerase chain reaction (PCR). The results indicated that all of 5 K. pneumoniae strains carried blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the resistant isolates markedly lacked the protein band of 34-40 kDa, which might be the outer membrane proteins of OmpK36 according to the electrophoresis mobility. In addition, the conjugation test was confirmed that blaDHA-1 mediated by plasmids could be transferred between resistant and sensitive strains. When reserpine (30 µg/mL) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 µg/mL) were added in imipenem and meropenem, the MICs had no change against K. pneumoniae strains. These results suggest that both DHA-1 β-lactamase and loss or deficiency of porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance in K. pneumoniae strains in our hospital

Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β

Background. Reducing β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer’s disease (AD). Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. Methods. We used Aβ1–42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA). Results. We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor α (TNF-α) and interleukin- (IL-) 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1) expression and brain-derived neurotrophic factor (BDNF) release, in the Aβ-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC) inhibitor partially abolished the nicotine-induced effects. Conclusion. These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Aβ via PKC

Association between serum estradiol levels and cognitive function in older women: a cross-sectional analysis

IntroductionEstradiol is a sex steroid hormone, which has been implicated in the pathogenesis of Alzheimer’s disease and cognitive impairment. This cross-sectional study aimed to examine the relationship between serum estradiol levels and cognitive performance in older American women.MethodsData were obtained from the National Health and Nutrition Examination Survey 2013–2014. A total of 731 women aged ≥60 years who met the inclusion criteria were included in this study. Serum estradiol levels were measured using the isotope dilution liquid chromatography tandem mass spectrometry (ID-LC–MS/MS) method developed by the Centers for Disease Control and Prevention for routine analysis. All measured serum levels were further divided into three parts: T1, <3.68 pg./mL; T2, 3.68–7.49 pg./mL; T3, >7.49 pg./mL, and analyzed. Participants’ cognitive abilities were tested using the Vocabulary Learning Subtest (CERAD), Animal Fluency Test (AFS), and digital symbol substitution test (DSST). Scores for each test were calculated based on the sample mean and standard deviation (SD). To examine the relationship between serum estradiol level tertiles and cognitive scores, multiple linear regression models were developed, controlling for race/ethnicity, education level, hypertension, diabetes, and insomnia.ResultsThe mean age of the participants was 69.57 ± 6.68 years. The non-Hispanic whites were 78.95%, and those who had completed at least some college-level education were 60.62%. The mean BMI of the participants was 29.30 ± 6.79, and 10.85% had a history of smoking. Further, 73.41% did not have a history of alcohol consumption, and 63.03% had hypertension (63.03%). In addition, 81.81 and 88.3% did not have a history of diabetes mellitus and did not have sleep disorders, respectively. The mean serum estradiol level was 8.48 ± 0.77 pg./mL. Multivariate linear regression of the reference group consisting of participants in tertiles of serum estradiol levels revealed that one unit increase in serum estradiol levels increased DSST scores by 0.61 (0.87, 6.34) in the T3 group. However, no significant correlation was found in the CERAD and AFS tests.ConclusionParticipants with higher estradiol levels had higher DSST scores and better processing speed, sustained attention, and working memory, suggesting that serum estradiol may serve as a biomarker for cognitive decline in older women

Orexigenic Hormone Ghrelin Attenuates Local and Remote Organ Injury after Intestinal Ischemia-Reperfusion

Gut ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area of the intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation of the vagus nerve can rapidly attenuate systemic inflammatory responses through inhibiting the activation of macrophages and endothelial cells. Ghrelin, a novel orexigenic hormone, is produced predominately in the gastrointestinal system. Ghrelin receptors are expressed at a high density in the dorsal vagal complex of the brain stem. In this study, we investigated the regulation of the cholinergic anti-inflammatory pathway by the novel gastrointestinal hormone, ghrelin, after gut I/R.Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 90 min in male adult rats. Our results showed that ghrelin levels were significantly reduced after gut I/R and that ghrelin administration inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival after gut I/R. Administration of a specific ghrelin receptor antagonist worsened gut I/R-induced organ injury and mortality. To determine whether ghrelin's beneficial effects after gut I/R require the intact vagus nerve, vagotomy was performed in sham and gut I/R animals immediately prior to the induction of gut ischemia. Our result showed that vagotomy completely eliminated ghrelin's beneficial effect after gut I/R. To further confirm that ghrelin's beneficial effects after gut I/R are mediated through the central nervous system, intracerebroventricular administration of ghrelin was performed at the beginning of reperfusion after 90-min gut ischemia. Our result showed that intracerebroventricular injection of ghrelin also protected the rats from gut I/R injury.These findings suggest that ghrelin attenuates excessive inflammation and reduces organ injury after gut I/R through activation of the cholinergic anti-inflammatory pathway

Research on hydraulic tension Fuzzy-PID control technology of mine belt conveyor

Aiming at the problems of slow response speed, poor regulation, time-varying and nonlinear tensioning control of traditional belt conveyor tensioning system in mine, a Fuzzy-PID control (PID control based on fuzzy algorithm) method of hydraulic tensioning system of belt conveyor in mine is proposed. Firstly, a mathematical model is established according to the hydraulic tensioning device, and secondly, the hydraulic tensioning system with Fuzzy-PID controller and PID controller are simulated by the built-in Simulink simulation library of Matlab, respectively, to derive the start-up response stage of the conveyor belt tensioning force and the regulation response graph of the sudden change of tension, and to make a comparative analysis. Finally, the effectiveness of the algorithm model is verified by experimental tests. The simulation results show that the hydraulic belt conveyor tensioning Fuzzy-PID control system has better steady state performance and faster response speed not only in the start-up phase but also during the sudden change of tension. The overshoot of tension in the start-up response phase of the tensioning device is reduced by 13.5%, and the time to reach the desired value is shortened by 0.5 s. The tension change of the tensioning device is the simulated tensioning and loosening stage, when the tension is increased, the speed of regulation of the Fuzzy-PID controller is shortened by 0.4 s, and the overshoot is reduced by 4%. When the tension decreases, the regulation speed of the Fuzzy-PID controller is shortened by 0.3 s and the overshoot is reduced by 2%. The experimental results show that the effect of using Fuzzy-PID control is better and more stable with less loss. Compared with PID control, Fuzzy-PID control is more effective, the average time is reduced by 31% and the overall tendency is stable. For the mine belt conveyor such as continuous transportation equipment, Fuzzy-PID control technology for the mine belt conveyor smooth operation provides a certain guarantee, not only reduces the waste of electricity, but also reduces the maintenance cost of maintenance belt conveyor

Machine learning to improve prognosis prediction of metastatic clear-cell renal cell carcinoma treated with cytoreductive nephrectomy and systemic therapy

Cytoreductive nephrectomy (CN) combined with systemic therapy is commonly used to treat metastatic clear-cell renal cell carcinoma (mccRCC). However, prognostic models for these patients are limited. In the present study, the clinical data of 782 mccRCC patients who received both CN and systemic therapy were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016), and patients were divided into training and internal test cohorts. A total of 144 patients who met the same criteria from our center (Peking Union Medical College Hospital) were placed in the external test cohort. The cancer-specific survival rate (CSS) at 1, 3, and 5 years was set as the research outcome. Then, four ML models, i.e., a gradient boosting machine (GBM), support vector machine (SVM), random forest (RF), and logistic regression (LR), were established. Fifteen potential independent features were included in this study.  Model performance was evaluated using the area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). Seven clinical features, namely pathological grade, T stage, N stage, number of metastatic sites, brain or liver metastases, and metastasectomy were selected for subsequent analysis via the recursive feature elimination (RFE) algorithm. In conclusion, the GBM model performed best at 1-, 3- and 5-year CSS prediction (0.836, 0.819 and 0.808, respectively in the internal test cohort and 0.819, 0.805 and 0.786, respectively in the external cohort). Furthermore, we divided the patients into three strata (high-, intermediate- and low-risk) via X-tile analysis and concluded that clinically individualized treatment can be aided by these practical prognostic models

Progress in Antarctic marine geophysical research by the Chinese Polar Program

Marine geophysical survey by the Chinese National Antarctic Research Expedition (CHINARE) began with the first science expedition in 1984/1985, although only four cruises were performed in the vicinity of the Antarctic Peninsula between then and 1991/1992. After a 20 year hiatus, Antarctic marine geophysical research was relaunched by the Chinese Polar Environmental Comprehensive Investigation and Assessment Programs (known simply as the Chinese Polar Program) in 2011/2012. Integrated geophysical surveys have been carried out annually since, in Prydz Bay and the Ross Sea. During the last 5 years, we have acquired about 5500 km of bathymetric, gravimetric, and magnetic lines; more than 1800 km of seismic reflection lines; and data from several heat flow and Ocean Bottom Seismometer (OBS) stations. This work has deepened understandings of geophysical features and their implications for geological tectonics and glacial history in Antarctica and its surrounding seas. Compiled Antarctic Bouguer and Airy isostatic gravity anomalies show different features of tectonics between the East Antarctic stability and West Antarctic activity. Calculated magnetic anomalies, heat flow anomalies and lithospheric anisotropy offshore of Prydz Bay may imply high heat capacity of mantle shielded by the continental shelf lithosphere, but high heat dissipation of mantle due to the Cretaceous breakup of Gondwana along the continent and ocean transition (COT), where large sediment ridges would be brought about by the Oligocene ice sheet retreat and would enlarge free-air gravity anomalies. In the western Ross Sea, CHINARE seismic profiles indicate northern termination of the Terror Rift and deposition time of the grounding zone wedge in the northern JOIDES Basin

Characteristics of fine particulate matter and its sources in an industrialized coastal city, Ningbo, Yangtze River Delta, China

Chemical information is essential in understanding the characteristics of airborne particles, and effectively controlling airborne particulate matter pollution, but it remains unclear in some regions due to the scarcity of measurement data. In the present study, 92 daily PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) samples as well as historical observation data of air pollutants were collected in urban Ningbo, one of important industrial cities in the coastal area of the Yangtze River Delta, China in autumn and winter (from Nov. 2014 to Feb. 2015). Various chemical species in PM2.5 were determined including water soluble ions, organic and elemental carbon and elements. Positive matrix factorization model, cluster analysis of back trajectories, potential source contribution function (PSCF) model and concentration-weighted trajectory (CWT) model were used for identifying sources, apportioning contributions from each source and tracking potential areas of sources. The results showed the PM2.5 concentration has been reducing; nonetheless, the concentrations of PM2.5 are still much higher than the World Health Organization guideline with high PM2.5 concentrations observed in autumn and winter for the past few years. During the sampling period, the average PM2.5 mass concentration was 77 μg/m3 with the major components of OC, NO3−, SO42 −, NH4+ and EC, accounting for 24.7, 18.8, 14.5, 11.8 and 6.4% in the total mass concentration, respectively. When the aerosol pollution got worse during the sampling period, the NO3−, SO42 − and NH4+ concentrations increased accordingly and NO3− appeared to increase at fastest rate. SO42 − transported from industrial areas led to slight difference in spatial distribution of SO42 − in Ningbo. More secondary organic carbon was formed and the enrichment factor values of Cu, Ag, Cd, Sn and Pb increased with the degradation of air quality. Ten types of sources were identified for PM2.5 in the autumn and winter of Ningbo, which are metallurgical industry, biomass burning and waste incineration, manufacturing related with Mo, chlor-alkli chemical industry, oil combustion, vehicular emission, secondary source, soil dust, road dust and manufacturing related with Cr, accounting for 9.4, 4.8, 9.4, 7.6, 8.1, 18.7, 27.6, 2, 7.1 and 5.2% of the total sources, respectively. There were five groups of air parcels arriving in Ningbo, of which inland air masses originating from Shandong province were associated with the highest PM2.5 concentrations. Despite the slight differences, it was obvious that the north of Jiangxi, east of Anhui, west of Jiangsu, south of Shandong were identified as major potential sources-areas of SO42 −, NO3−, NH4+, Cl−, OC and EC by both PSCF and CWT models