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Background: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795.Objectives: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795.Methods: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795.Results: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795.Conclusions: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795.Trial Registration: Vupanorsen is a GalNAc3-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non–high-density lipoprotein cholesterol [non–HDL-C]), and safety were assessed.Absorption of vupanorsen was rapid (median time to maximum concentration [Tmax]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [Cmax]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were – 59.7% and – 69.5% for ANGPTL3, – 41.9% and – 52.5% for TG, and – 23.2% and – 25.4% for non–HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.ClinicalTrials.gov identifier: NCT04916795. [ABSTRACT FROM AUTHOR]

Because the valence state of metal with variable valences is sensitive to oxidation atmosphere, it is difficult to fabricate single-phased metal oxide with intermediate valence by vapor or vacuum deposition. In this work, the copper valence state in oxides was controlled by introducing a nitrogen flow into the sputtering chamber. The surface chemical potential of oxygen can be efficiently tuned through adsorption competition on the growth surface. The transition process from CuO–Cu2O mixture to single Cu2O was observed with increasing the nitrogen flow rate. For the single-phased Cu2O, the hole concentration was tuned in a range of 2.6 × 1017 to 1.1 × 1018 cm−3. [ABSTRACT FROM AUTHOR]

Fe-3.3Si-6.5Cr powders were first treated by phosphoric acid solution and then mixed with epoxy-modified silicone resin uniformly, forming insulation coating. The Fe-3.3Si-6.5Cr soft magnetic composites were prepared by compaction and annealing treatment of the coated Fe-3.3Si-6.5Cr powders. The microstructure and composition of Fe-3.3Si-6.5Cr powders were analyzed by scanning electron microscope coupled with energy-dispersive spectrometer, Fourier-transform infrared spectra, and X-ray photoelectron spectroscopy, respectively. The magnetic properties were determined by the LCR bridge tester and an auto testing system for magnetic materials (MATS-2010SA). Results show that both proper phosphating treatment and annealing at higher temperature can improve the permeability and reduce the core loss of the Fe-3.3Si-6.5Cr SMCs. When the concentration of phosphoric acid was 0.5 wt% and the heat treatment temperature reached 500 °C, the Fe-3.3Si-6.5Cr SMCs showed the optimized magnetic properties, including the permeability (μe) of 44.7 H/cm, the core loss (P) of 521.8 mW/cm3 at the saturated magnetic flux density of 50 mT, and the frequency of 100 kHz. The Fe-3.3Si-6.5Cr SMCs with distinguished magnetic properties provide great application prospect in various fields such as filter inductors, transformers, and sensors. [ABSTRACT FROM AUTHOR]

A systematic strategy of absorbing boundary conditions for molecular dynamics simulations are presented. The exact boundary conditions for crystalline solids with harmonic approximation are expressed as a dynamic Dirichlet-to-Neumann (DtN) map. It connects the displacement of the atoms at the boundary to the traction on these atoms. The DtN map is valid for a domain with general geometry. To avoid evaluating the time convolution of the dynamic DtN map, we approximate the associated kernel function by rational functions in the Laplace domain. The parameters in the approximations are determined by interpolations. The explicit forms of the zeroth, first, and second order approximations will be presented. The stability of the molecular dynamics model, supplemented with these absorbing boundary conditions is established. Two numerical simulations are performed to demonstrate the effectiveness of the methods. [ABSTRACT FROM AUTHOR]

To screen the stable expression genes related to the stress (strong light, dehydration and temperature shock) we applied Absolute real-time PCR technology to determine the transcription numbers of the selected test genes in P orphyra yezoensis, which has been regarded as a potential model species responding the stress conditions in the intertidal. Absolute real-time PCR technology was applied to determine the transcription numbers of the selected test genes in P orphyra yezoensis, which has been regarded as a potential model species in stress responding. According to the results of photosynthesis parameters, we observed that Y(II) and F/ F were significantly affected when stress was imposed on the thalli of P orphyra yezoensis, but underwent almost completely recovered under normal conditions, which were collected for the following experiments. Then three samples, which were treated with different grade stresses combined with salinity, irradiation and temperature, were collected. The transcription numbers of seven constitutive expression genes in above samples were determined after RNA extraction and cDNA synthesis. Finally, a general insight into the selection of internal control genes during stress response was obtained. We found that there were no obvious effects in terms of salinity stress (at salinity 90) on transcription of most genes used in the study. The 18S ribosomal RNA gene had the highest expression level, varying remarkably among different tested groups. RPS8 expression showed a high irregular variance between samples. GAPDH presented comparatively stable expression and could thus be selected as the internal control. EF-1α showed stable expression during the series of multiple-stress tests. Our research provided available references for the selection of internal control genes for transcripts determination of P. yezoensis. [ABSTRACT FROM AUTHOR]

Model predictive control (MPC) is recognized as an efficient control method for the modular multilevel converter (MMC), owing to its advantages, such as good robustness, rapid dynamic response, and multi-objective control. However, due to the coupling relationship between the ac-side current and the circulating current, the existing MPC has an impact on the ac-side current while suppressing the circulating current. In this paper, the relationship between the ac-side current performance and circulating current suppression is discussed in detail, and a three-stage MPC (TS-MPC) strategy is proposed to optimize the comprehensive performance. With the ac-side current control, circulating current control, and comprehensive optimization control, the optimum performance of both the ac-side current and circulating current suppression is realized while maintaining a low computational burden. Moreover, a grouping sorting algorithm is designed to reduce the calculation burden and to balance the capacitor voltages. The steady-state and transient performances of the proposed TS-MPC strategy have been verified by experimental results, which validates its correctness and effectiveness. [ABSTRACT FROM AUTHOR]

To address the technical limitations of automatic coal and gangue detection technology in fully mechanized top coal caving mining operations, the low radiation level radioactivity measurement method is utilized to assess the degree of coal-gangue mixture in top coal caving process. This approach is based on the distinguishing radiation characteristics of natural γ-rays between coal and gangue. This study analyzed the distribution characteristics of natural γ-rays in coal and rock layers of thick coal seams and the applicability of this method, introduced the basic principle of coal-gangue detection technology based on natural γ-ray, developed the test system about automatic coal-gangue detection, studied the radiation characteristics of coal and gangue, proposed determination model of the coal-gangue mixed degree, combined with the time sequence characteristics of the top coal's releasing flow and the energy spectrum characteristics of different layers of rock, realized the precise coal-gangue detection technology in complex structure thick coal seam with multiple gangue. Field tests were conducted in Lilou, Xiaoyu and Tashan Coal Mine. The test results were well corroborated with the research results and achieved the expected results, which laid the foundation for the field application of intelligent coal mining. [ABSTRACT FROM AUTHOR]

Introduction: Levornidazole is a novel nitroimidazole antimicrobial agent active against anaerobes. We aimed to investigate the pharmacokinetic (PK) profile of levornidazole after single and multiple oral doses of levornidazole tablets in healthy Chinese subjects and propose the dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods: A single-center, randomized, double-blind, placebo-controlled study was conducted with a single ascending dose (250, 500, 1000, and 1500 mg) and multiple doses of 500 mg levornidazole q12h for 7 days. Food effect on PK and absolute bioavailability were investigated at the 500 mg dose level. Blood and urine samples were collected to determine the PK parameters of levornidazole. The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated by Monte Carlo simulation to predict the clinical efficacy of levornidazole tablets. Results: Plasma concentration reached peak about 0.5 h after single dose (250–1500 mg) of levornidazole tablets. The maximal concentration (Cmax) and exposure (AUC0–∞) of levornidazole increased linearly with dose. High-fat diet did not affect the absorption extent of levornidazole tablets. The absolute oral bioavailability of levornidazole tablets was 98.3% ± 7.6%, associated with large apparent volume of distribution (48.68 ± 4.92 l) and long half-life (11.93 ± 1.28 h). The urinary excretion of levornidazole was 7.99%. Levornidazole, administered at either 500 mg q12h or 750 mg q24h, achieved a CFR > 95.4% and PTA > 99% for B. fragilis (minimum inhibitory concentration ≤ 1.0 mg/l) infections. Conclusion: Levornidazole tablets are absorbed rapidly and completely and distributed extensively with a long half-life and low urinary excretion after a single dose or multiple doses in healthy Chinese subjects. Levornidazole tablets can be taken with or without food. Levornidazole tablets 500 mg q12h and 750 mg q24h are expected to achieve the desired efficacy in B. fragilis infections. Clinical Trail Registration: Trial registration number CTR20160786 at http://www.chinadrugtrials.org.cn/. [ABSTRACT FROM AUTHOR]

Compared with the single-phase wireless power transfer systems, the three-phase wireless power transfer systems have the advantages of large transfer power, high position offset tolerance, and small output ripple, etc., which have been widely used for high-power application. For a three-phase rail-type dynamic wireless power transfer system, the interphase cross-coupling mutual inductance, will lead to three-phase unbalance, difficult modeling and analysis. So, a new type of three-phase rail-type magnetic coupling structure is proposed and optimized. Firstly, a magnetic coupling structure for a three-phase rail-type dynamic wireless power transfer system is proposed. Secondly, the physical principle and mathematical tools are used to calculate the primary and secondary equivalent parameters of the system, and a fully decoupled equivalent mathematical model of the system is established. Thirdly, based on the model, the output characteristics of the system such as power and efficiency are analyzed. Finally, an experimental platform for a 1 kW three-phase rail-type dynamic wireless power transfer system is built to verify the theoretical analysis. The experimental results show that the magnetic coupling structure proposed in this paper can well solve the problem of system imbalance caused by interphase cross-coupling mutual inductance, and improve the power and efficiency of the system. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tegoprazan is one of the potassium-competitive acid blockers (P-CABs). It exhibits its anti-secretory effects by competitively and reversibly blocking the availability of K+ of the H+, K+-ATPase. This study was designed to investigate the safety and pharmacokinetics of tegoprazan in healthy Chinese subjects. Methods: Thirty-eight healthy Chinese subjects were recruited in this randomized, single-center, double-blind, placebo-controlled study, with a single ascending dose of 50, 100, 200 mg and a multiple dose of 100 mg for 10 days. The plasma concentration of tegoprazan was determined by a validated liquid chromatography tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetics were evaluated via non-compartmental and compartmental model analysis. Safety was assessed by physical examinations, vital signs, clinical laboratory tests, and electrocardiograms. Results: No serious adverse event was observed in this study. After single-dose administration (50, 100 and 200 mg), tegoprazan was rapidly absorbed with a median maximum measure plasma concentration (Tmax) at 0.5 h and declined with a terminal (elimination) half-life (t1/2) of 3.87–4.57 h. The maximum measured plasma concentration (Cmax) for tegoprazan was 813.80, 1494.60 and 2829.00 ng/mL. Meanwhile, the corresponding area under the concentration–time curve (AUC) from time zero to infinity (AUC0−inf) was 2761.00, 5980.05 and 11,044.72 ng∙h/mL in 50, 100, 200 mg group, respectively. Dose-dependent increase was observed in the value of Cmax and AUC after administration of tegoprazan 50 to 200 mg. The two-compartment model well described the pharmacokinetic profile of tegoprazan. In the steady state, no accumulation was found after repeated administration at the 100-mg dose level. No experimental differences were found based on gender. Conclusions: Tegoprazan was well tolerated in the dose range of 50–200 mg in single- and 100 mg in multiple-dose studies. Tegoprazan shows dose linearity with oral administration after a single dose of 50 to 200 mg and less drug accumulation after 10 days of continuous administration in 100 mg. [ABSTRACT FROM AUTHOR]

Transfer efficiency is one of the most significant indexes of magnetic coupling wireless power transfer (MC-WPT) systems, which is severely affected by frequency splitting. In this paper, a novel method is proposed for MC-WPT systems to achieve the maximum transfer efficiency by introducing and controlling the circuit detuning factors while maintaining the operating frequency at constant. Firstly, the circuit model of tri-coil MC-WPT systems is established along with the derivation of some key concepts, including the transfer efficiency and circuit detuning factors. Then the analytical expressions of the optimal circuit detuning factors, maximum transfer efficiency and a comprehensive discriminant which could quickly and accurately determine the critical value for every system parameters are derived. Further, the physical interpretation of the maximum transfer efficiency is firstly elucidated from the perspective of energy flow: (1) when the system is in non-splitting region, the energy flow path of the maximum transfer efficiency is transmitter–relay–receiver; (2) when system is in splitting region, the energy flow path of the maximum transfer efficiency is directly from the transmitter to the receiver. Finally, simulation models and practical prototypes are designed to verify the theoretical results. The simulation and experimental results show that the proposed system can maintain an almost constant maximum transfer efficiency over a wide range of transfer distance. The derived discriminant is very useful for guiding the system design in the future, and the energy flow analysis method will be beneficial for maximizing the efficiency for multi-coil MC-WPT systems. [ABSTRACT FROM AUTHOR]