Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that ...the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction–related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired β2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.
•Hyperuricemia suppresses neutrophil adhesion and extravasation during sterile inflammation.•Uric acid impairs neutrophil migration by suppressing β2 integrin activity/recycling and cytoskeletal dynamics upon urate transporter–mediated uric acid uptake.
Display omitted
As a typical representative of the third-generation semiconductor materials, GaN is an ideal substrate for the fabrication of blue-green lasers, RF microwave devices, and power electronic devices. ...The application of substrate materials cannot be separated from the post-treatment of materials. Although wet etching and thermal annealing are not necessary steps, they have great research value for GaN crystals. This review systematically reviews the importance of wet etching in GaN crystal applications, which can not only characterize the dislocations and study the crystal defects, but can also rapidly remove the damaged layer, improve the grinding and polishing efficiency, and achieve a smooth and non-damaged surface, so as to improve the performance of GaN-based devices. After thermal annealing of the GaN crystal, the surface quality will be improved, stress relaxation will occur, and the photoelectric properties will be significantly improved. Finally, the challenges and opportunities of the wet etching and thermal annealing of GaN crystals are briefly described, and their development prospects are noted.
This manuscript systematically reviews the importance of wet etching and thermal annealing in GaN crystal applications for the first time.
Assess the efficiency and cost-effectiveness of infliximab, cyclosporine and tacrolimus for the treatment of ulcerative colitis (UC).
A literature search identified studies that investigated ...infliximab, cyclosporine or tacrolimus compared with placebo in UC patients. Short-term, long-term remission rates and response rates were employed to assess efficacy. Odds ratios with 95% confidence intervals were analyzed. A Markov model was constructed to simulate the progression in a cohort of patients with UC, with an over 10 years of time horizon, with a discount rate of 3%, and established threshold of €30,000/quality-adjusted life-year (QALY) or ¥82442/QALY.
Results of network meta-analysis showed that the order was cyclosporine, tacrolimus, infliximab and placebo from high rate to low with regard to short-term clinical response. The comparison between infliximab versus cyclosporine achieved an incremental cost effectiveness ratio (ICER) of €184435/QALY and ¥531607/QALY, with a 0.34893 QALYs difference of efficacy, and an incremental cost of €64355 and ¥185494. Tacrolimus versus cyclosporine reached an ICER of €44236/QALY and ¥57494/QALY, with a difference of 0.40963 QALYs in efficacy, and a raising cost to €18120 and ¥23551. The probabilistic sensitivity analysis shows that cyclosporine would be cost-effective in the 75.8% of the simulations, tacrolimus in the 24.2%, and infliximab for the 0%.
Infliximab, cyclosporine and tacrolimus as salvage therapies are efficacious. For long-term of clinical remission, the order of pharmacological agents was tacrolimus, infliximab and cyclosporine from high efficacy to low while no significant difference is seen. In cost-effectiveness analysis, the cyclosporine versus infliximab or tacrolimus is expected to be at best.
Purpose
The purpose of this paper is to study the effect of current-carrying condition on the electrochemical process and atmospheric corrosion behavior of the commercial aluminum alloys.
...Design/methodology/approach
Potentiodynamic polarization tests were performed to study the electrochemical process of the aluminum alloys. Salt spray tests and weight loss tests were carried out to study the atmospheric corrosion behavior. The corrosion morphology of the alloys was observed, and the products were analyzed.
Findings
The corrosion process of four aluminum alloys was accelerated in the current-carrying condition. Moreover, the acceleration effect on A2024 and A7075 was much stronger than that on A1050 and A5052. The main factors would be the differences in microstructure and corrosion resistance between these alloys. As the carried current increased, the corrosion rate and corrosion current density of the aluminum alloys gradually increased, with the protection of the corrosion product film decreasing linearly.
Originality/value
This is a recent study on the corrosion behavior of conductors under current-carrying condition, which truly understands the corrosion status of power grid materials. Relevant results provide support for the corrosion protection and safe service of aluminum alloy in power systems.
We designed this study to investigate the effects of the coronavirus disease 2019 (COVID-19) vaccine on epileptic seizures, as well as its adverse effects, in children with epilepsy (<18 years).
This ...anonymous questionnaire study involved a multicenter prospective survey of outpatients and inpatients with epilepsy (＜18 years) registered in epilepsy clinics in eight hospitals in six cities of Shandong Province.
A total of 224 children with epilepsy were included in the study. Fifty of them experienced general adverse events after vaccination. The most common local adverse events were pain or tenderness at the injection site. The most common systemic adverse effects were muscle soreness and headache. No severe adverse events were reported. There were no significant differences in the number of antiseizure medications (P = 0.459), gender (P = 0.336), etiology (P = 0.449), age (P = 0.499), duration of disease (P = 0.546), or seizure type (P = 0.475) between the patients with and without general adverse events. We found that the risk of seizure after vaccination was decreased in children who were seizure free for more than six months before vaccination. There was no significant difference in the number of seizures during the first month before vaccination, the first month after the first dose, and the first month after the second dose (P = 0.091).
The benefits of vaccination against COVID-19 outweighed the risks of seizures/relapses and severe adverse events after vaccination for children with epilepsy.
To study pharmacokinetic parameters and absolute bioavailability for oral use of sinomenine tablet in beagle dogs.
Applying to double cycle self crossover design, a single oral or intravenous dose of ...10 mg x kg(-1) sinomenine was given to 10 beagle dogs. Drug concentrations in plasma were determined by HPLC. The pharmacokinetic parameters were calculated by 3P97 pharmacokinetic program.
The concentration-time curves of oral administration fitted to one compartment model in the beagle dogs. The T(max), C(max), t1/2 and AUC(0-T) was (82.5 +/- 13.9) min, (0.15 +/- 0.027) mg x L(-1), (87.6 +/- 28.3) min and (28.43 +/- 3.48) mg x min x L(-1), respectively. The concentration -time curves of i.v. fitted to two compartment model in the beagle dogs. The t1/2beta and AUC(0-T) was (106.7 +/- 120.2) min and (93.32 +/- 82.08) mg x min x L(-1). The absolute bioavailability for oral use was (30.46 +/- 4.24)%.
The absolute bioavailability of sinomenine is low, and the elimination of sinomenine tablet is fast.
Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant genetic disorder involving multiple organ systems and primarily characterized by structural brain abnormalities and ...a distinctive facial appearance.
To study the clinical characteristics, gene types and seizures of BWCFF. The natural history, clinical data and peripheral blood sample were collected in the child and his patients. To screen the β-actin gene (ACTB) of a newly diagnosed child, hoping to find the gene mutation.
The child had left ptosis, ocular hypertelorism, arched eyebrows, only 30% of the left ear hearing, a slight hypotonia, normal muscle strength, walking instability. The seizures were difficult to control with antiepileptic drugs and presented some degree of psychomotor development delay. Genetic screening showed De Novo in ACTB gene (c.484A> G, p.Thr162Ala). Parents did not detect related gene mutations.
Patients with typical facial features and cerebral cortical malformations associated with refractory epilepsy should be highly suspected BWCFF. Patients are advised to carry out genetic screening to confirm the diagnosis.
Contrary to a previous report, electron microscopic studies on the Fny strain of cucumber mosaic virus (CMV)-infected tobacco tissues revealed that plasmodesmata were not structurally modified during ...CMV infection, nor were virions ever observed in plasmodesmata connecting infected cells. To further explore the basis of CMV infection, experiments were performed on the CMV 3a ORF. The 3a protein of CMV was expressed in and purified from
Escherichia coli. The purified protein was labeled with fluorescein isothiocyanate (FITC) and subsequently microinjected into mesophyll cells of mature leaves of
Nicotiana tabacum cv. Turkish Samsun NN. Within a brief period (as little as 1 sec), the microinjected FITC-labeled CMV 3a protein moved into neighboring cells. Co-injection of unlabeled CMV 3a protein with 9.4-kDa fluorescein-conjugated dextran (F-dextran) resulted in extensive cell-to-cell movement (diffusion) of the F-dextran, indicating that the 3a protein can interact with and dilate plasmodesmata. Furthermore, co-injection of unlabeled 3a protein with fluorescently labeled infectious CMV RNA molecules resulted in rapid and extensive cell-to-cell transport. In contrast, a mutant form of the 3a protein was unable to traffic from cell to cell, to increase the size exclusion limit of plasmodesmata, or to potentiate cell-to-cell trafficking of CMV RNA molecules. Microinjection studies performed on transgenic tobacco plants expressing the CMV 3a protein indicated that fluorescently labeled CMV RNA moved out of the target cell into the surrounding mesophyll tissue. In addition, expression of the CMV 3a protein also potentiated the cell-to-cell movement of 9.4-kDa F-dextran. Collectively, these results provide direct experimental evidence that the CMV 3a protein functions as the movement protein of CMV. These findings are consistent with the hypothesis that CMV moves from cell-to-cell in the form of a ribonucleoprotein complex.
PDF