Influence of Zn Addition on the Aging Precipitate Behavior and Mechanical Properties of Al-Cu-Li Alloy.

In the present work, the effect of Zn on the aging precipitates and mechanical properties of Al-Cu-Li alloys was investigated by Vickers hardness, tensile tests, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The results indicated that the addition of Zn reduced the activation energy of the T1 phase and makes it easier to precipitate. The activation energy of the T1 phase, which was 107.02 ± 1.8 KJ/mol, 94.33 ± 1.7 KJ/mol, 90.33 ± 1.7 KJ/mol and 90.28 ± 1.6 KJ/mol for 0Zn, 0.4Zn, 0.8Zn and 1.2Zn alloy, respectively. The area number density of the T1 precipitate ranged from 97.0 ± 4.4 pcs/µm2 to 118.2 ± 2.8 pcs/µm2 as the Zn content increased from 0 to 1.2 wt.%. Consequently, the addition of Zn promoted the precipitation of the T1 phase. Therefore, the peak hardness and tensile strength of the alloy also increased with the increase in the Zn content, and the hardness of the alloy with Zn content of 1.2 wt.% increased by 16.5 ± 1.4 HV; meanwhile, the ultimate tensile strength increased by 46.5 ± 2.5 MPa. Therefore, the area number density of precipitates increased and improved the strength of the Zn-containing alloy.

Effects of Different Heating and Cooling Rates during Solution Treatment on Microstructure and Properties of AA7050 Alloy Wires.

In the present study, the effects of varying heating and cooling rates during the solution treatment process on the microstructure and properties of AA7050 alloy wires were investigated using tensile tests, metallographic microscopy, electron backscattered diffraction, and transmission electron microscopy. It was found that the recrystallized grain size of the alloy, subjected to method of rapid heating, exhibited a smaller and more uniform distribution in comparison to method of slow heating. The low density of η' strengthening phases after the artificial aging treatment was formed using air cooling method. Meanwhile, by using the water quenching method sufficient solute atoms and more nucleation sites were provided resulting in a large number of η' strengthening phases being formed. In addition, the alloy processed using the water quenching method displayed higher strength than that treated using the air cooling method for the T6 and T73 states. Furthermore, coarse precipitates formed and less clusters were observed in the matrix, while high density nanoscale clusters and no continuous precipitation are formed when using the water quenching method.

Effects of Cu Addition on Age Hardening Behavior and Mechanical Properties of High-Strength Al-1.2Mg-1.2Si Alloy.

In this study, the effects of Cu addition on artificial age hardening behavior and mechanical properties of Al-1.2Mg-1.2Si-(xCu) alloy was investigated quantitatively and qualitatively by Vickers hardness, tensile test, and transmission electron microscope. The results indicated that Cu addition enhanced the aging response of the alloy at 175 °C. With the increase in Cu content, the time for the alloys to reach peak aging decreased from 12 h to 10 h and 8 h. The tensile strength of the alloy was obviously improved with Cu added in which was 421 MPa of 0Cu alloy, 448 MPa of 0.18Cu alloy, and 459 MPa of 0.37Cu alloy. The results of TEM observation revealed that the addition of 0.37Cu changed the aging precipitation sequence of the alloy, in which the precipitation sequence of 0Cu and 0.18Cu alloy was SSSS→GP zones/pre-ß″→ß″→ß″ + ß', 0.37Cu alloy was SSSS→GP zones/pre-ß″→ß″ + L→ß″ + L + Q'. Moreover, with the addition of Cu, the number density and volume fraction of precipitates of the Al-1.2Mg-1.2Si-(xCu) alloy was evidently increased. The number density was increased from 0.23 × 1023/m3 to 0.73 × 1023/m3 in the initial aging stage and from 1.9 × 1023/m3 to 5.5 × 1023/m3 in the peak aging stage. The volume fraction was increased from 0.27% to 0.59% in the early aging stage and from 4.05% to 5.36% in the peak aging stage. It indicated that Cu addition promoted the precipitation of strengthening precipitates and boosted the mechanical properties of the alloy accordingly.

Microstructure, Precipitates Behavior, and Mechanical Properties of Age-Hardened Al-Mg-Si Alloy Sheet Fabricated by Twin-Roll Casting.

Twin-roll casting (TRC), as a near-net-shape technology, is employed to fabricate age-hardened Al-Mg-Si alloy. Compared with conventional direct chill (DC) casting, the TRC method is much more economical and efficient. In this work, the microstructure, precipitates behavior, and mechanical properties of age-hardened Al-Mg-Si alloy sheet fabricated by TRC were investigated by hardness measurements and tensile tests, metallographic microscopy, field emission gun scanning electron microscope, electron backscatter diffraction, transmission electron microscopy, and differential scanning calorimetry analyses. It was found that the size of recrystallized grains for DC casting alloy with finely dispersed particles was larger than that of TRC alloy with coarse particles. Typical CubeND texture accompanied by P texture formed after solution treatment made the value of r reach ~0.7 in the TRC alloy due to the PSN effect caused by the segregation of particles. More GP zones resulted in the strength of TRC alloy being higher than that of DC casting alloy after T8X treatment. With the time of paint-bake hardening extended to 8 h, few segregation particles remained in the TRC alloy. This decreased the concentration of supersaturated atoms. The hardness of the TRC alloy with the lower density of the ß″ strengthening phase was lower compared to the DC casting alloy.

Concurrent pigeon paramyxovirus-1 and Acinetobacter baumannii infection in a fatal case of pneumonia.

Pigeon paramyxovirus type 1 (PPMV-1), an antigenic variant of avian paramyxovirus type 1 (APMV-1), mainly infects pigeons. PPMV-1 genotype VI is the dominant genotype infecting pigeons in China. Human infection of avian paramyxovirus was rarely reported, and usually developed mild symptoms, such as conjunctivitis. We detected PPMV-1 in the lower respiratory sample from a fatal case with severe pneumonia; this patient aged 64 years presented cough, fever, and haemoptysis for 8 days and was admitted to hospital on Dec 26, 2020. He developed acute respiratory distress syndrome and sepsis in the following days and died of multiple organ failure on Jan 7, 2021. Sputum and blood culture reported multidrug-resistant Acinetobacter baumannii (ABA) for samples collected on days 22 and 19 post-illness, respectively. However, clinical metagenomic sequencing further reported PPMV-1 besides ABA in the bronchoalveolar lavage fluid. The PPMV-1 genome showed 99.21% identity with a Chinese strain and belonged to VI genotype by BLAST analysis. Multiple basic amino acids were observed at the cleavage site of F protein (113RKKRF117), which indicated high virulence of this PPMV-1 strain to poultry. The patient had close contact with pigeons before his illness, and PPMV-1 nucleic acid was detected from the pigeon feather. PPMV antibody was also detected in the patient serum 20 days after illness. In conclusion, concurrent PPMV-1 genotype VI.2.1.1.2.2 and ABA infection were identified in a fatal pneumonia case, and cross-species transmission of PPMV-1 may occur between infected pigeons and the human being.

Pulmonary benign metastasizing leiomyoma: a case report and literature review.

Benign metastasizing leiomyoma (BML) is a rare condition that occurs mainly in premenopausal women and is characterized most commonly by pulmonary metastases. Here, we report the case of a 45-year-old woman who presented with multiple bilateral pulmonary nodules on chest examination during a health checkup 13 years after myomectomy. This patient has a normal menstrual cycle, moderate anemia, and no obvious respiratory symptoms. Serum concentrations of cancer markers such as carcinoembryonic antigen, neuron specific enolase, cytokeratin 19 fragments, and pro-gastrin-releasing peptide were within normal limits. Color doppler ultrasound was also performed, several hypoechoic regions were found in uterine bodies and cavity. The computed tomography (CT)-guided lung biopsy was used for histopathological examination. Immunohistochemical staining revealed BML which were positive for smooth muscle antibody, desmin, vimentin, estrogen and progesterone receptors, and Ki-67 positive rate of about 1%. Hysterectomy and bilateral adnexectomy were performed as a part of treatment. The lung nodules were meticulously monitored at follow-up. Three months later, the repeat CT scan showed that the nodules had reduced in size, and no new nodules had appeared, 1 year later, CT scan showed no obvious changes in lung nodules. This study is of great significance as the results will be helpful in diagnosing and treating future pulmonary benign metastasizing leiomyoma (PBML) cases.

Accurate nucleic acid quantification in a single sample tube without the need for calibration.

Convenient and accurate nucleic acid quantification (NAQ) is crucial to clinical diagnosis, forensic medicine, veterinary medicine and food analysis. However, traditional NAQ relies on the preparation of a laborious, time-consuming and expensive calibration curve, which would also propagate pipette errors through serially dilutions. Besides, traditional NAQ is run in different tubes, which introduces bias from random tube-to-tube variations and is unable to detect inhibitors from biological samples. To solve these problems, a single-tube quantitative PCR (stqPCR) technique is proposed which enables accurate quantification without the need for a calibration curve. In this method, an internal quantitative standard DNA (IQS-DNA) for quantification was screened out by co-amplification with the target DNA. Then the difference between the quantification cycle value (ΔCq) of the IQS-DNA and the target DNA was used for NAQ. The method permitted high accuracy quantification with reliable data for concentrations in plasmid, serum standard, and clinical samples being confirmed (R2 values of 0.9951, 0.9889, and 0.9727, slope values of 1.011, 1.028, and 0.9327, and intercept values of -0.06037, -0.1486, and 0.3325, respectively). Accurate NAQ could also be achieved by stqPCR even though inhibitors were present in a sample; however, in the case of using a commercial assay kit, satisfactory performance was only attained after the same sample was diluted some 32-fold. Moreover, integration of the present method into a microfluidic system could achieve super-fast NAQ in less than 30 min and achieve super-fast "sample in, quantitative answer out" testing in less than 40 min. Thus, the stqPCR method present here would promote the development of NAQ in the laboratory and on site.

An environmentally-friendly, highly efficient, gas pressure-assisted sample introduction system for ICP-MS and its application to detection of cadmium and lead in human plasma.

An environmentally friendly and highly efficient gas pressure-assisted sample introduction system (GPASIS) was developed for inductively-coupled plasma mass spectrometry. A GPASIS consisting of a gas-pressure control device, a customized nebulizer, and a custom-made spray chamber was fabricated. The advantages of this GPASIS derive from its high nebulization efficiencies, small sample volume requirements, low memory effects, good precision, and zero waste emission. A GPASIS can continuously, and stably, nebulize 10% NaCl solution for more than an hour without clogging. Sensitivity, detection limits, precision, long-term stability, double charge and oxide ion levels, nebulization efficiencies, and matrix effects of the sample introduction system were evaluated. Experimental results indicated that the performance of this GPASIS, was equivalent to, or better than, those obtained by conventional sample introduction systems. This GPASIS was successfully used to determine Cd and Pb by ICP-MS in human plasma.

Expression of voltage-gated potassium channels in human and rhesus pancreatic islets.

Voltage-gated potassium channels (Kv channels) are involved in repolarization of excitable cells. In pancreatic beta-cells, prolongation of the action potential by block of delayed rectifier potassium channels would be expected to increase intracellular free calcium and to promote insulin release in a glucose-dependent manner. However, the specific Kv channel subtypes responsible for repolarization in beta-cells, most importantly in humans, are not completely resolved. In this study, we have investigated the expression of 26 subtypes from Kv subfamilies in human islet mRNA. The results of the RT-PCR analysis were extended by in situ hybridization and/or immunohistochemical analysis on sections from human or Rhesus pancreas. Cell-specific markers were used to show that Kv2.1, Kv3.2, Kv6.2, and Kv9.3 are expressed in beta-cells, that Kv3.1 and Kv6.1 are expressed in alpha-cells, and that Kv2.2 is expressed in delta-cells. This study suggests that more than one Kv channel subtype might contribute to the beta-cell delayed rectifier current and that this current could be formed by heterotetramers of active and silent subunits.

Selenium speciation using capillary electrophoresis coupled with modified electrothermal atomic absorption spectrometry after selective extraction with 5-sulfosalicylic acid functionalized magnetic nanoparticles.

A new method for selenium speciation in fermented bean curd wastewater and juice was described. This method involved sample extraction with 5-sulfosalicylic acid (SSA)-functionalized silica-coated magnetic nanoparticles (SMNPs), capillary electrophoresis (CE) separation, and online detection with a modified electrothermal atomic absorption spectrometry (ETAAS) system. The modified interface for ETAAS allowed for the introduction of CE effluent directly through the end of the graphite tube. Elimination of the upper injection hole of the graphite tube reduced the loss of the anlayte and enhanced the detection sensitivity. The SSA-SMNPs were synthesized and used to extract trace amounts of selenite [Se(IV)], selenite [Se(VI)], selenomethionine (SeMet), and selenocystine (SeCys2) from dilute samples. The concentration enrichment factors for Se(VI), Se(IV), SeMet, and SeCys2 were 21, 29, 18, and 12, respectively, using the SSA-SMNPs extraction. The limits of detection for Se(VI), Se(IV), SeMet, and SeCys2 were 0.18, 0.17, 0.54, 0.49ngmL(-1), respectively. The RSD values (n=6) of method for intraday were observed between 0.7% and 2.9%. The RSD values of method for interday were less than 3.5%. The linear range of Se(VI) and Se(IV) were in the range of 0.5-200ngmL(-1), and the linear ranges of SeMet and SeCys2 were 2-500 and 2-1000ngmL(-1), respectively. The detection limits of this method were improved by 10 times due to the enrichment by the SSA-SMNP extraction. The contents of Se(VI) and Se(IV) in fermented bean curd wastewater were measured as 3.83 and 2.62ngmL(-1), respectively. The contents of Se(VI), Se(IV), SeMet, and SeCys2 in fermented bean curd juice were determined as 6.39, 4.08, 2.77, and 4.00ngmL(-1), respectively. The recoveries were in the range of 99.14-104.5% and the RSDs (n=6) of recoveries between 0.82% and 3.5%.

Functional assay of voltage-gated sodium channels using membrane potential-sensitive dyes.

The discovery of novel therapeutic agents that act on voltage-gated sodium channels requires the establishment of high-capacity screening assays that can reliably measure the activity of these proteins. Fluorescence resonance energy transfer (FRET) technology using membrane potential-sensitive dyes has been shown to provide a readout of voltage-gated sodium channel activity in stably transfected cell lines. Due to the inherent rapid inactivation of sodium channels, these assays require the presence of a channel activator to prolong channel opening. Because sodium channel activators and test compounds may share related binding sites on the protein, the assay protocol is critical for the proper identification of channel inhibitors. In this study, high throughput, functional assays for the voltage-gated sodium channels, hNa(V)1.5 and hNa(V)1.7, are described. In these assays, channels stably expressed in HEK cells are preincubated with test compound in physiological medium and then exposed to a sodium channel activator that slows channel inactivation. Sodium ion movement through open channels causes membrane depolarization that can be measured with a FRET dye membrane potential-sensing system, providing a large and reproducible signal. Unlike previous assays, the signal obtained in the agonist initiation assay is sensitive to all sodium channel modulators that were tested and can be used in high throughput mode, as well as in support of Medicinal Chemistry efforts for lead optimization.

Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia.

BACKGROUND: Extended-release niacin/laropiprant (ERN/LRPT) reduces flushing and preserves the lipid-modifying effects of ERN. This study compared the efficacy and safety of ERN/LRPT plus simvastatin (ERN/LRPT+SIMVA) with atorvastatin (ATORVA) in patients with mixed hyperlipidemia. METHODS: After a 4-week placebo run-in, 2340 patients (LDL-C ≥ 130 and ≤ 190 mg/dL, TG ≥ 150 and ≤ 500 mg/dL and above NCEP ATP III risk-based LDL-C goal) were randomized to 1 of 6 treatment arms: ERN/LRPT 1g/20mg+SIMVA (10 or 20mg), or ATORVA (10, 20, 40, or 80 mg) once daily. RESULTS: At Week 12, ERN/LRPT+SIMVA was superior to ATORVA in decreasing LDL-C/HDL-C (primary endpoint) at each pre-specified dose comparison: ERN/LRPT+SIMVA 20mg vs. ATORVA 10mg (-13.2%; p<0.001); ERN/LRPT+SIMVA 40 mg vs. ATORVA 20mg (-10.8%; p<0.001); ATORVA 40 mg (-5.1%; p<0.001); and ATORVA 80 mg (-4.2%; p=0.007). At Week 12, ERN/LRPT+SIMVA was superior to ATORVA in increasing HDL-C and reducing TG for all pre-specified treatment comparisons, and reducing non-HDL-C and LDL-C for the ERN/LRPT+SIMVA 20mg versus ATORVA 10mg and ERN/LRPT+SIMVA 40 mg versus ATORVA 20-mg dose comparisons, but not the ERN/LRPT+SIMVA 40 mg versus ATORVA 40- and 80-mg dose comparisons. Adverse experiences (AEs) typically associated with niacin (flushing, pruritus, increased glucose, increased uric acid) were more common with ERN/LRPT+SIMVA, and hepatic-related laboratory AEs were more common with ATORVA. CONCLUSION: ERN/LRPT+SIMVA was generally superior to ATORVA in improving lipid parameters after 12 weeks and was generally well tolerated in patients with mixed hyperlipidemia.

Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels.

Voltage-gated potassium (Kv) channels regulate many physiological functions and represent important therapeutic targets in the treatment of several clinical disorders. Although some of these channels have been well-characterized, the study of others, such as Kv3 channels, has been hindered because of limited pharmacological tools. The current study was initiated to identify potent blockers of the Kv3.2 channel. Chinese hamster ovary (CHO)-K1 cells stably expressing human Kv3.2b (CHO-K1.hKv3.2b) were established and characterized. Stichodactyla helianthus peptide (ShK), isolated from S. helianthus venom and a known high-affinity blocker of Kv1.1 and Kv1.3 channels, was found to potently inhibit 86Rb+ efflux from CHO-K1.hKv3.2b (IC50 approximately 0.6 nM). In electrophysiological recordings of Kv3.2b channels expressed in Xenopus laevis oocytes or in planar patch-clamp studies, ShK inhibited hKv3.2b channels with IC50 values of approximately 0.3 and 6 nM, respectively. Despite the presence of Kv3.2 protein in human pancreatic beta cells, ShK has no effect on the Kv current of these cells, suggesting that it is unlikely that homotetrameric Kv3.2 channels contribute significantly to the delayed rectifier current of insulin-secreting cells. In mouse cortical GABAergic fast-spiking interneurons, however, application of ShK produced effects consistent with the blockade of Kv3 channels (i.e., an increase in action potential half-width, a decrease in the amplitude of the action potential after hyperpolarization, and a decrease in maximal firing frequency in response to depolarizing current injections). Taken together, these results indicate that ShK is a potent inhibitor of Kv3.2 channels and may serve as a useful pharmacological probe for studying these channels in native preparations.

Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic beta-cells.

Voltage-gated potassium (Kv) currents of human pancreatic islet cells were studied by whole-cell patch clamp recording. On average, 75% of the cells tested were identified as beta-cells by single cell, post-recording RT-PCR for insulin mRNA. In most cells, the dominant Kv current was a delayed rectifier. The delayed rectifier activated at potentials above -20 mV and had a V(1/2) for activation of -5.3 mV. Onset of inactivation was slow for a major component (tau = 3.2 s at +20 mV) observed in all cells; a smaller component (tau = 0.30 s) with an amplitude of approximately 25% was seen in some cells. Recovery from inactivation had a tau of 2.5 s at -80 mV and steady-state inactivation had a V(1/2) of -39 mV. In 12% of cells (21/182) a low-threshold, transient Kv current (A-current) was present. The A-current activated at membrane potentials above -40 mV, inactivated with a time constant of 18.5 ms at -20 mV, and had a V(1/2) for steady-state inactivation of -52 mV. TEA inhibited total Kv current with an IC50 = 0.54 mm and PAC, a disubstituted cyclohexyl Kv channel inhibitor, inhibited with an IC50 = 0.57 microm. The total Kv current was insensitive to margatoxin (100 nm), agitoxin-2 (50 nm), kaliotoxin (50 nm) and ShK (50 nm). Hanatoxin (100 nm) inhibited total Kv current by 65% at +20 mV. Taken together, these data provide evidence of at least two distinct types of Kv channels in human pancreatic beta-cells and suggest that more than one type of Kv channel may be involved in the regulation of glucose-dependent insulin secretion.