Summary
Hepatitis B virus surface antigen (HBsAg) plays an important role in maintaining the tolerance and may interfere with host innate and adaptive immune responses; therefore, novel therapeutic ...strategies to reduce HBsAg loads in patients infected with hepatitis B virus (HBV) are emerging as an attractive but challenging issue. Metformin could regulate hepatic metabolism while the latter interacts with HBV infection. We hypothesized that metformin could affect HBsAg expression and HBV replication and may work synergistically when combined with current antivirals. In our study, a notably inhibitory effect on HBsAg production, as well as a moderate inhibition in HBV replication and HBeAg expression was observed following metformin treatment. The 50% effective concentration (EC50) for extracellular HBsAg and intracellular HBsAg in HBV‐producing HepG2.2.15 cells was 2.85 mm and 2.75 mm, respectively, with a similarly selective index of about 18. When administered in combination, metformin enhanced the inhibitory effects of interferon‐α2b on HBsAg expression and HBV replication and provided a complimentary role in HBsAg expression for lamivudine (LMV). This novel action of metformin derives partially from its inhibition on multiple HBV cis‐acting elements. By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HBsAg production inhibitor.
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
High-β_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the ...Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-β_{θe} regime.
To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors.
H. pylori strains were collected from ...patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method.
H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China.
The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.
Tire-road friction coefficient is an important parameter for vehicle stability and active safety systems. However, precise measurement of tire-road friction coefficient is hard to achieve without ...expensive equipment. Considering easy availability and good economy, this paper proposes a method which first combines auxiliary particle filter and the iterated extended kalman filter (APF-IEKF), and then processes the results of the first step using iteration algorithm. APF-IEKF is used to estimate the slip angle of the front tires with strong nonlinearity and non-Gaussian noise, in which APF filters non-Gaussian noise and reach a preliminary estimation of sideslip angle, then IEKF is used to optimize the result, making the estimation of the sideslip angle more accurate. The iteration algorithm is used to estimate the tire-road friction coefficient based on self-aligning torque, which is more sensitive to tire slip angle and provides faster estimation. In this way, this method can estimate tire road friction coefficient more accurately and in real time. Both numerical simulation in Carsim/Simulink and actual off-vehicle tests in winter are provided to demonstrate the efficiency of the proposed algorithm.
•A method that combines APF-IEKF and iteration algorithm is proposed for tire-road friction coefficient.•Tire slip angle estimated by APF-IEKF is much more accurate than common UKF because it is fit for non-Gaussian noise.•Tire-road friction coefficient estimate by proposed method is also much more accurate.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
We re-estimate the peculiar velocity of the Sun with respect to the local standard of rest (LSR) using a sample of local stars within 600 pc of the Sun, selected from the Large Sky Area Multi-Object ...Fiber Spectroscopic Telescope (LAMOST, also named the Guoshoujing Telescope) Spectroscopic Survey of the Galactic Anti-centre (LSS-GAC). The sample consists of 94 332 FGK main-sequence stars with well-determined radial velocities and atmospheric parameters. To derive the LSR, two independent analyses are applied to the data. First, we determine the solar motion by comparing the observed velocity distribution to that generated with the analytic formulism of Schönrich & Binney that has been demonstrated to show excellent agreement with rigorous torus-based dynamics modelling by Binney & McMillan. Secondly, we propose that cold populations of thin disc stars, selected by applying an orbital eccentricity cut, can be directly used to determine the LSR without the need of asymmetric drift corrections. Both approaches yield consistent results of solar motion in the direction of Galactic rotation, V
⊙, that are much higher than the standard value adopted hitherto, derived from Strömgren's equation. The newly deduced values of V
⊙ are 1–2 km s−1 smaller than the more recent estimates derived from the Geneva–Copenhagen Survey (GCS) sample of stars in the solar neighbourhood (within 100 pc). We attribute the small difference to the presence of several well-known moving groups in the GCS sample that, fortunately, hardly affect the LSS-GAC sample. The newly derived radial (U
⊙) and vertical (W
⊙) components of the solar motion agree well with the previous studies. In addition, for all components of the solar motion, the values yielded by stars of different spectral types in the LSS-GAC sample are consistent with each other, suggesting that the local disc is well relaxed and that the LSR reported in the current work is robust. Our final recommended LSR is, (U⊙, V⊙, W⊙) = (7.01 ± 0.20, 10.13 ± 0.12, 4.95 ± 0.09) km s−1.
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. ...However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
This study investigated the extent of heavy metal accumulation in leaf vegetables and associated potential health risks in agricultural areas of the Pearl River Delta (PRD), South China. Total ...concentrations of mercury (Hg), cadmium (Cd), lead (Pb), chromium (Cr) and arsenic (As) were determined in 92 pairs of soil and leaf vegetable (flowering Chinese cabbage, lettuce, pakchoi, Chinese cabbage, loose-leaf lettuce, and Chinese leaf mustard) samples collected from seven agricultural areas (cities). The bioconcentration factors (BCF) of heavy metals from soil to vegetables were estimated, and the potential health risks of heavy metal exposure to the PRD residents through consumption of local leaf vegetables were assessed. Results showed that among the six leaf vegetables, pakchoi had the lowest capacity for heavy metal enrichment, whereas among the five heavy metals, Cd had the highest capacity for transferring from soil into vegetables, with BCF values 30-fold those of Hg and 50-fold those of Cr, Pb and As. Sewage irrigation and fertilization were likely the main sources of heavy metals accumulated in leaf vegetables grown in agricultural areas of the PRD region. Different from previous findings, soil pH had no clear effect on metal accumulation in leaf vegetables. Despite a certain degree of metal enrichment from soil to leaf vegetables, the PRD residents were not exposed to significant health risks associated with consumption of local leaf vegetables. Nevertheless, more attention should be paid to children due to their sensitivity to metal pollutants.
Since December 2019, the novel coronavirus disease 2019 (COVID-19) that emerged in Wuhan city has spread rapidly around the world. The risk for poor outcome dramatically increases once a patient ...progresses to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in individuals with mild to moderate COVID-19.
We conducted a cohort study that included 1007 individuals with mild to moderate COVID-19 from three hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients were followed up for 28 days for observation of disease progression. The end point was the progression to a more severe disease stage.
During a follow up of 28 days, 720 patients (71.50%) had recovered or were symptomatically stable, 222 patients (22.05%) had progressed to severe disease, 22 patients (2.18%) had progressed to the critically ill stage and 43 patients (4.27%) had died. Multivariate Cox proportional hazards models identified that increased age (hazard ratio (HR) 2.56, 95% CI 1.97–3.33), male sex (HR 1.79, 95% CI 1.41–2.28), presence of hypertension (HR 1.44, 95% CI 1.11–1.88), diabetes (HR 1.82, 95% CI 1.35–2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38–2.93) and coronary artery disease (HR 1.83, 95% CI 1.26–2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34–0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02–2.90), urea nitrogen (HR 1.72, 95% CI 1.21–2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26–7.21) and D-dimer (HR 2.01, 95% CI 1.12–3.58) at baseline were also associated with risk for disease progression.
This study identified a panel of risk factors for disease progression in individuals with mild to moderate COVID-19.
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