Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Effect of the <i>PmARF6</i> Gene from Masson Pine (<i>Pinus massoniana</i>) on the Development of <i>Arabidopsis</i>

Masson pine (Pinus massoniana) is a core industrial tree species that is used for afforestation in southern China. Previous studies have shown that Auxin Response Factors (ARFs) are involved in the growth and development of various species, but the function of ARFs in Masson pine is unclear. In this research, we cloned and identified Masson pine ARF6 cDNA (PmARF6). The results showed that PmARF6 encodes a protein of 681 amino acids that is highly expressed in female flowers. Subcellular analysis showed that the PmARF6 protein occurred predominantly in the nucleus and cytomembrane of Masson pine cells. Compared with wild-type (WT) Arabidopsis, transgenic Arabidopsis plants overexpressing PmARF6 had fewer rosette leaves, and their flower development was slower. These results suggest that overexpression of PmARF6 may inhibit the flower and leaf development of Masson pine and provide new insights into the underlying developmental mechanism

Design and Operating Mode Study of a New Concept Maglev Car Employing Permanent Magnet Electrodynamic Suspension Technology

Based on the principle of permanent magnet electrodynamic suspension (PMEDS), a new concept maglev car was designed by using rotary magnetic wheels and a conductor plate. It has the advantages of being high-speed, low-noise, environmentally friendly, safe and efficient. The PMEDS car is designed to use a permanent magnet electrodynamic wheel (EDW) to achieve the integration of levitation force and driving force. The levitation force is generated by the repulsive force of the eddy current magnetic field, and the driving force is generated by the reaction force of magnetic resistance. A simplified electromagnetic force model of the EDW and a dynamics model of the PMEDS car were established to study the operating mode. It shows that the PMEDS car can achieve suspension when the rotational speed of the EDWs reaches a certain threshold and the critical speed of the EDWs is 600 rpm. With the cooperation of four permanent magnet EDWs, the PMEDS car can achieve stable suspension and the maximum suspension height can reach 7.3 mm. The working rotational speed of EDWs is 3500 rpm. At the same time, the movement status of the PMEDS car can be controlled by adjusting the rotational speed of rear EDWs. The functions of propulsion, acceleration, deceleration, and braking are realized and the feasibility of the PMEDS car system is verified

Experimental Study of the Flow Mechanism of Deep Lacustrine Carbonate Reservoirs in the Yingxi Area of the Qaidam Basin

Many of the exploration and development theories derived for conventional clastic rock reservoirs are not applicable to pore-fracture lacustrine carbonate reservoirs. The fluid flow mechanisms under reservoir conditions are still unclear. Therefore, in this study, the rock samples were characterized using X-ray diffraction (XRD), porosity-permeability analysis, scanning electron microscopy (SEM), plain thin sections, and casting thin sections. The core samples were classified into two types (fractures and matrix pores) based on their reservoir spaces. The core flow experiments were performed under reservoir conditions using reservoir core plugs. The experimental results demonstrate that the cores, especially the fractured cores, have a strong stress sensitivity. The oil phase flow in the core has the characteristics of non-Darcy flow, and the threshold pressure gradient is 0.01–0.003 MPa/m. Additionally, for the oil-water two-phase flow in the fractured core, the water phase relative permeability of the residual oil is high. In contrast, the water phase relative permeability of the matrix core is less than 0.2. The nuclear magnetic resonance (NMR) transverse relaxation time (T2) spectra were used to analyze the differences between the water flooding characteristics of the two pore structures. The experimental results show that the peaks of the T2 spectra after water flooding are lower than those before water flooding, and the matrix cores have a better oil displacement effect. The relaxation time of 0.1–10 ms makes the greatest contribution to the water flooding efficiency. The micropores smaller than 10 μm in diameter play an important role in the water flooding of the matrix core. These results will provide theoretical basis for solving the difficult problems of developing deep lacustrine carbonate reservoirs