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Infectious diseases pose a major challenge to human health, and there is an urgent need to develop new antimicrobial agents with excellent antibacterial activity. A series of novel triazolo[4,3-a]pyrazine derivatives were synthesized and their structures were characterized using various techniques, such as melting point, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. All the synthesized compounds were evaluated for in vitro antibacterial activity using the microbroth dilution method. Among all the tested compounds, some showed moderate to good antibacterial activities against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli strains. In particular, compound 2e exhibited superior antibacterial activities (MICs: 32 μg/mL against Staphylococcus aureus and 16 μg/mL against Escherichia coli), which was comparable to the first-line antibacterial agent ampicillin. In addition, the structure–activity relationship of the triazolo[4,3-a]pyrazine derivatives was preliminarily investigated. [ABSTRACT FROM AUTHOR]

SiC P /Al composite is regarded as a superior alternative material in the aerospace industry due to its excellent properties. Meanwhile, electrically-assisted aging (EAA) heat treatment has emerged as a promising method for artificial aging to obtain better aging performances. This study explores the potential of EAA heat treatment to enhance the aging kinetics of SiC P /Al composite. The impact of EAA on the aging behavior of SiC P /AA2009 composites is investigated and compared with conventional furnace aging treatment, ranging from microstructure to macroscopic properties. The electric current has few effects on the evolution trend of aging strength, but can enhance the aging process of SiC P /AA2009 with higher yield strength (about 13.7 MPa improvement) and ultimate tensile strength (about 9.7 MPa improvement). Analysis of microstructures demonstrates that EAA can generate more nucleation sites and reduce consumption of Cu atoms by Cu–Mg co-clusters near SiC P interface, resulting in more θ' phases compared to conventional aging (CA). Additionally, more fine precipitates and dislocations contribute to higher strength under EAA condition. Subsequently, a precipitation kinetic model based on the Lagrange-like approach is employed to predict the particular electric current effects on the particle size distribution and evolution during aging, and to calculate yield strength by establishing a relationship between microstructural characteristics and macroscopic performance, providing a model basis for the design of potential EAA processes. [ABSTRACT FROM AUTHOR]

This paper investigated the cyclic plasticity of AA6014-T4P with the tension-compression (T-C) and compression-tension (C-T) cyclic loading tests. A new compression-induced softening behavior is found and modeled. Specifically, the material was softened permanently during the tensile load when a compressive pre-strain was applied, whereas such an abnormal phenomenon was not observed when the loading sequence is reversed. Moreover, the magnitude of the permanent softening scale linearly with the compressive pre strain. Therefore, we term this phenomenon as compression-induced softening in this paper. Based on this compression-induced softening phenomena, a modified Y–U model is formulated by introducing a correction factor that modifies the hardening rate of the boundary surface to describe the permanent softening effect, which can predict the compression-induced softening well. Our work reveals a new phenomenon for the cyclic loading of metal sheets and stimulates further efforts on the path-dependence of metal plasticity. [Display omitted] • Cyclic tension-compression (T-C) and compression-tension (C-T) tests were performed for 6014-T4P aluminum alloys. • An anomalous compression-induced softening behavior of AA6014-T4P was revealed during cyclic loading. • The plastic compressive pre strain is linear with the permanent softening stress drop. • A modified Y–U model was proposed to successfully capture the compression-induced softening behavior. [ABSTRACT FROM AUTHOR]

Electrically-assisted (EA) forming is an effective method to improve forming quality of sheet metal. In order to reveal the effects of current on material flow behavior under complex strain paths and develop corresponding constitutive model, the EA tension-compression cyclic loading tests with particularly designed setup were carried out. Then, the effects of current on the elastic modulus degradation and cyclic deformation were investigated. Further, corresponding modulus degradation model and constitutive model were developed. The results showed that the flow stress under EA uniaxial tension was lower than that under warm uniaxial tension. Moreover, the current-induced growth of precipitate and the decrease of dislocation occur under EA uniaxial tension. Regarding the EA cyclic deformation behavior, the elastic modulus decreases with the increase of plastic strain, temperature and current density, which is described by a proposed modified modulus degradation model. The Bauschinger effect and permanent softening effect are weakened with the increase of temperature and current density. The asymmetric tension-compression behavior becomes more obvious with the increase of temperature and current density. Based on above results, a modified Y-U model was established and verified with EA draw-bending process. The above research work can provide some research basis for the application of electrically-assisted forming. • Non-thermal effect was confirmed in electrically-assisted forming of 7075-T6. • An electrically-assisted (EA) tension-compression cyclic loading test device was developed. • A proposed modified elastic modulus model could well predict the elastic modulus under different conditions. • Unique permanent softening, flow asymmetry and transient Bauschinger effect during EA cyclic loading were revealed. • A modified Y-U model suitable for EA tension-compression cyclic loading was proposed and verified. [ABSTRACT FROM AUTHOR]

A rapid and sensitive Ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of fourteen alkaloids in beagle dog plasma after a single oral dose of the Corydalis bungeana Turcz (C. bungeana) extract selected bifendate as the internal standard (IS). The plasma samples were preprocessed by liquid-liquid extraction (LLE) with aether before separation on an Agilent SB-C18 column (1.8 µm, 150 × 2.1 mm) using a gradient elution program. The mobile phase consists of 0.2% acetic acid and acetonitrile at the flow rate of 0.3 mL/min. In the positive ion mode, the analytes were detected by multiple reaction monitoring (MRM). The results indicated that calibration curves for fourteen analytes have good linearity (R2 = 0.9904). The lower limits of quantification (LLOQ) of fourteen alkaloids and IS were all over 4.87 ng/mL and the matrix effects ranged from 94.08% to 102.76%. The mean extraction recoveries of Quality control samples at low (LQC), medium (MQC) and high (HQC) and IS were all more than 78.03%. The intra- and inter-day precision (R.S.D.%) also met the criterion, at the same time the deviation of assay accuracies (R.E) ranged from −13.70% to 14.40%. The Tmax values of fourteen alkaloids were no more than 1 h. The range of Cmax was from 74.16 ± 8.71 to 2256 ± 255.9 ng/mL. The assay was validated in the light of the regulatory bioanalytical guidelines and proved acceptable, which was successfully applied to a pharmacokinetic study of these compounds in beagle dogs after oral administration of Corydalis bungeana Turcz extract. [ABSTRACT FROM AUTHOR]

Sheet metals usually experience various loading paths such as uniaxial tension, uniaxial compression, biaxial tension, and simple shear during the forming process. However, the existing constitutive models cannot always accurately describe blanks' anisotropic yield and plastic flow behavior of blanks under all typical stress states. Given this, this paper improves the Eyld2000-2d yield criterion by introducing hydrostatic pressure to the A-Eyld2000-2d yield criterion that can describe the strength differential effect of materials. Meanwhile, to control the curvature of the yield surface more effectively, the near-plane strain yield stresses were added in the parameter identification process to calibrate the exponent m, so that the exponent is no longer considered as a constant value. Taking the widely used AA6016-T4, AA5754-O, DP980, and QP980 blanks in the automotive stamping industry as an example, the effectiveness of the new model and different parameter identification methods was verified by predicting experimental data under various simple and complex loading paths. Subsequently, the new model employing the optimal parameter identification strategy was compared with four widely used asymmetric yield criteria under associated and non-associated flow rules, including CPB06, LHY2013, S-Y2004, and Hu & Yoon2021, to further verify the accuracy of the proposed constitutive model. The results indicate that parameter identification strategy with variable exponent can significantly improve the flexibility of the yield criterion in describing the plastic anisotropy of blanks. Compared to the other yield criteria examined in this work, the new model provides the best prediction accuracy for the yield stresses and plastic flows of all blanks, especially in the near-plane strain and simple shear stress states. Modeling under the concept of anisotropic hardening can more accurately capture the evolving plastic behavior of blanks than isotropic hardening. [ABSTRACT FROM AUTHOR]

Objective: A sensitive and rapid ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was successfully applied to the determination of 10 alkaloids in beagle dog plasma following a single oral dose of Xiatianwu capsules and enteric‐coated capsules, with theophylline serving as the internal standard (IS). Methods: Plasma samples were preprocessed using liquid–liquid extraction (LLE) with ethyl acetate ahead to separation using a gradient elution procedure on a Waters ACQUITY UPLC HSS T3 column (1.8 μm, 100 × 2.1 mm). The mobile phase was composed of 0.1% formic acid solution and acetonitrile at the flow rate of 0.3 ml/min. Multiple reaction monitoring (MRM) was used to determine the analytes in the positive ion mode. Results: The calibration curves for 10 analytes demonstrated a high degree of linearity (r ≥ 0.9920). The lower limit of quantification (LLOQ) values for 10 alkaloids were all more than 1.074 ng/ml, and matrix effects varied from 94.25% to 106.15%. The mean extraction recovery of quality control samples at low (LQC), medium (MQC) and high (HQC) concentrations, as well as IS, was all more than 76.60%. The intra‐day and inter‐day precision (RSD) also satisfied the requirement. Simultaneously, the variation of assay accuracies (RE) was between 13.05% and 9.38%. Conclusion: The test was validated in accordance with regulatory bioanalytical guidelines and was found to be suitable for use in a pharmacokinetic investigation of these compounds in beagle dogs after oral administration of Xiatianwu general capsules and enteric‐coated capsules. The Cmax of 10 alkaloids ranged from 52.61 to 192.46 ng/ml after oral administration of Xiatianwu capsules, and from 67.50 to 247.36 ng/ml. The Tmax was between 0.59 and 1.33 h of Xiatianwu capsules, and between 1.08 and 2.00 h of enteric‐coated capsules. The t1/2 ranged from 3.18 to 7.47 h of general capsules, and from 6.01 to 11.36 h. AUC0‐t ranged from 181.06 to 722.74 ng·h/ml of Xiatianwu capsules, and from 275.03 to 884.17 ng·h/ml of enteric‐coated capsules. The Cmax of enteric‐coated capsules were significantly increased except for tetrahydropalmatine and berberine. Tmax of general capsules were less than 1 h, and of enteric‐coated capsules were less than 2 h. The t1/2 of dehydrocorydaline, palmatine, tetrahydrojatrorrhizine, jatrorrhizine and coptisine in enteric‐coated capsules was longer than that in ordinary capsule. The AUC0‐t and AUC0‐∞ of bicuculline, dehydrocorydaline, protopine, magnoflorine, tetrahydrojatrorrhizine, jatrorrhizine, berberine and coptisine were all significantly higher in enteric‐coated capsules. [ABSTRACT FROM AUTHOR]

Primary membrane nephropathy (PMN) and IgA nephropathy (IgAN) are the most common glomerular diseases in China. Because of different pathogenesis, prognosis is significantly different. When the two diseases coexist (PMN/IgAN), the clinicopathological manifestations and prognosis remain unclear. In the present study, we analyzed the clinicopathological characteristics of PMN/IgAN patients, with only IgA deposition (PMN/IgA deposition) patients as controls. Galactose-deficient IgA1(KM55) and M-type Phospholipase A2 Receptor(PLA2R), both in circulation and renal tissues, were detected. Furthermore, prognosis of PMN/IgAN was explored. We found that PMN/IgAN also had some clinical features of IgAN in addition to PMN, such as higher serum albumin, along with a similar heavy proteinuria and lower titers of serum anti-PLA2R antibody. The positive rate of glomerular KM55 in PMN/IgAN was 23.5% (20/85), and 0% (0/29) in PMN/IgA deposition. Among those glomerular KM55 positive patients, KM55 and IgA colocalized mainly along the glomerular mesangial and capillary areas. Unfortunately, there was no significant difference in serum level of Gd-IgA1 between KM55+ and KM55− subgroups in PMN/IgAN patients, similar to the PMN/IgA deposition group. Notably, glomerular KM55 positive may predict a poorer prognosis in PMN/IgAN patients. In conclusion, our study suggested that, when glomerular KM55 staining was positive, this special coexisting PMN/IgAN disorder was prone to have more characteristics of IgAN besides PMN, and may predict poorer prognosis, while the mechanism requires further investigation. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the underlying pathological muscle damage in neuromyelitis optica spectrum disorder (NMOSD) patients without muscular symptoms. We prospectively enrolled 15 patients with aquaporin 4 (AQP4) antibody seropositive NMOSD and 16 patients with non-NMOSD diseases as a control group. Biceps biopsy samples from 18 patients were examined. Six NMOSD patients exhibited inflammatory lesions/edema in lower muscles on muscle MRI. On histopathological examination, NMOSD samples showed significantly decreased IgG-targeting AQP4 expression on sarcolemma compared with non-NMOSD samples in terms of the area of positive staining and integrated optical density. Muscle biopsy can support the differential diagnosis of NMOSD. Unlabelled Image • NMOSD rarely manifests as symptomatic muscle damage. • Aquaporin 4-IgG seropositive NMOSD exhibits underlying muscular pathological damage • Muscle specimens in NMOSD show decreased AQP4-targeting IgG expression in sarcolemma. • Muscle biopsy can support the differential diagnosis of NMOSD. [ABSTRACT FROM AUTHOR]

This study has developed a sensitive and simple ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of corydaline, dehydrocorydaline, tetrahydropalmatine, protopine, palmatine, tetrahydroberberine, columbamine, berberine, coptisine and berberrubine in beagle dog plasma after the oral administration of the Corydalis yanhusuo W.T. Wang and Yuanhuzhitong tablets. Chromatographic separation was achieved on an Agilent Eclipse Plus C18 RRHD column (1.8 µm, 50 × 2.1 mm) using a gradient elution program with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection was conducted by multiple reaction monitoring (MRM) mode via an electrospray ionization source in the positive mode. The calibration curves of all analytes showed good linear (r2 > 0.9800). The intra-day and inter-day precisions were less than 15% and the accuracies were within ±15%. The extraction recoveries conformed to the acceptable range. And there was no interference of endogenous substances in the sensitive assay method. All analytes were proven to be stable during sample storage and analysis procedures. The pharmacokinetic study indicated that the Yuanhuzhitong tablets could get a better absorption than Corydalis yanhusuo W.T. Wang. [ABSTRACT FROM AUTHOR]

In this study, the constituents of a Corydalis bungeana Turcz extract were qualitatively analyzed using gradient elution with a mobile phase of 0.2% acetic acid and acetonitrile. We obtained comprehensive insight into the constituents of C. bungeana Turcz extracts through the quantitative analysis of 14 compounds by comparison with authentic reference standards, and tentatively identified an additional 44 compounds through electrospray ionization mass spectrometry (ESI–MS) and tandem MS detection. The separation was successfully achieved using an Agilent SB-C18 column (1.8 µm, 150 × 2.1 mm; Agilent, Santa, CA, USA). A tandem quadrupole spectrometer was operated in either full-scan mode or multiple reaction monitoring (MRM) for the qualitative and quantitative analyses of the constituents, respectively. Validation data (inter-day and intra-day combined) for accuracy and precision ranged from −4.80% to 4.73%, and 0.30% to 4.97%, respectively. An ultrahigh performance liquid chromatographic–ESI–tandem MS (UHPLC–ESI–MS/MS) method for qualitative of C. bungeana Turcz (C. bungeana) extract and the quantification of 14 alkaloids, namely, A–N, was developed and validated. Quantitative analysis involved gradient elution with a mobile phase of 0.1% acetic acid and methanol for 45 min. The separation was successfully achieved using a Waters SB-C18 column (1.8 µm, 100 mm × 2.1 mm, Waters, Milford, Massachusetts, USA). The repeatability and stability of the method also met USFDA criteria with CV values lower than 5%. The limit of detection of the 14 alkaloids ranged from 9.74 to 13.00 ng/mL, whereas the linearities of the standard curves were between 0.9991 and 0.9995. In total, 15 commercial samples from 11 different sources were analyzed. [ABSTRACT FROM AUTHOR]

Coptidis rhizoma (CR) is the dried rhizome of the ranunculaceous plant CR. For decades in China, this plant has been used to treat hypertension, hyperlipidemia, and chronic diarrhea and has been officially included in the Chinese Pharmacopoeia. The present paper presents a review of the pharmacokinetics of CR. The pharmacokinetic studies and differences of 10 alkaloids among Coptis deltoidea C. Y. cheng et Hsiao, Coptis chinensis Franch and Coptis teeta Wall. Are seldom reported. This study is the first to determine corydaline, dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine, which adopted an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, simultaneously. Chromatographic separation was performed within 8 min by using an Agilent SB-C 18 column (150 mm × 2.1 mm, 1.8 μm) with gradient mobile phase consisting of 0.3% acetic acid water (v / v) and acetonitrile at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode was used to detect the tandem mass spectrum in the positive ionization mode by electrospray ionization source. The method was fully validated to be linear over a wide concentration (r > 0.9916), and the linear concentration range was 0.195–2260 ng/mL. Intra- and interday precisions were below 14.19% and 18.56% for the 10 analytes, respectively. The accuracy ranged from −9.30% to 6.31%. The extraction recovery of the 10 alkaloids and internal standard ranged from 79.76% to 95.37%. Pharmacokinetic comparative study showed that the C max and AUC 0-∞ values of dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine increased significantly (p < 0.05), which was different for beagles after oral administration. The results can help determine the mechanism of action and guide clinical application of these three extracts. This validated method was successfully applied for the pharmacokinetics study of beagle plasma after oral administration of three CR extract types. Image 1 [ABSTRACT FROM AUTHOR]

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester (II), 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (III), rosamultin (IV), 1β-hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid–liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from −9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58–1.58 h), and then eliminated relatively slowly (t1/2, 6.86–11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis. [ABSTRACT FROM AUTHOR]