Pharmacokinetic, acute toxicity, and pharmacodynamic studies of semen strychni total alkaloid microcapsules

Purpose: To investigate the safety and effectiveness of semen strychni total alkaloid microcapsules (SSTAM), compared with semen strychni total alkaloids (SSTA). Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to assess pharmacokinetics of brucine and strychnine in rats. Acute toxicity was investigated in pre-test and formal experiments in mice. The pharmacodynamics of SSTAM and SSTA were evaluated by their analgesic and anti-inflammatory activities. Results: With respect to brucine, the half-life of SSTA group (1.6 mg/kg), low-dose SSTAM group (6 mg/kg) and high-dose SSTAM group (10 mg/kg) was 5.723, 9.321 and 9.025 h, respectively. With respect to strychnine, the half-life of SSTA group, low-dose SSTAM group and high-dose SSTAM group was 4.065, 8.819 and 8.654 h, respectively. The LD50 values of SSTAM group and SSTA group were 236.59 and 30.27 mg/kg, respectively. The pain inhibition rates of SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group (p < 0.05) while the pain threshold values of the SSTAM groups (25 and 50 mg/kg) were higher than that of blank control (p < 0.01) and SSTA groups (p < 0.01) at 60 min and 120 min. The inhibition rates of the SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group based on ear swelling and cotton ball granulation tests. Compared with blank control and SSTA groups, the absorbance values of SSTAM groups (25 and 50 mg/kg) were lower (p < 0.01). Conclusion: SSTAM increases the dosage of administration but reducea the toxicity of the alkaloids in rats, and is thus a potentially safe and effective drug delivery system

TiG-BEV: Multi-view BEV 3D Object Detection via Target Inner-Geometry Learning

To achieve accurate and low-cost 3D object detection, existing methods propose to benefit camera-based multi-view detectors with spatial cues provided by the LiDAR modality, e.g., dense depth supervision and bird-eye-view (BEV) feature distillation. However, they directly conduct point-to-point mimicking from LiDAR to camera, which neglects the inner-geometry of foreground targets and suffers from the modal gap between 2D-3D features. In this paper, we propose the learning scheme of Target Inner-Geometry from the LiDAR modality into camera-based BEV detectors for both dense depth and BEV features, termed as TiG-BEV. First, we introduce an inner-depth supervision module to learn the low-level relative depth relations between different foreground pixels. This enables the camera-based detector to better understand the object-wise spatial structures. Second, we design an inner-feature BEV distillation module to imitate the high-level semantics of different keypoints within foreground targets. To further alleviate the BEV feature gap between two modalities, we adopt both inter-channel and inter-keypoint distillation for feature-similarity modeling. With our target inner-geometry distillation, TiG-BEV can effectively boost BEVDepth by +2.3% NDS and +2.4% mAP, along with BEVDet by +9.1% NDS and +10.3% mAP on nuScenes val set. Code will be available at https://github.com/ADLab3Ds/TiG-BEV.Comment: Code link: https://github.com/ADLab3Ds/TiG-BE

Experimental and Theoretical Study on the OH-Reaction Kinetics and Photochemistry of Acetyl Fluoride (CH3C(O)F), an Atmospheric Degradation Intermediate of HFC-161 (C2H5F)

The direct reaction kinetic method of low pressure fast discharge flow (DF) with resonance fluorescence monitoring of OH (RF) has been applied to determine rate coefficients for the overall reactions OH + C2H5F (EtF) (1) and OH + CH3C(O)F (AcF) (2). Acetyl fluoride reacts slowly with the hydroxyl radical, the rate coefficient at laboratory temperature is k(2)(300 K) = (0.74 +/- 0.05) x 10(-14) cm(3) molecule(-1) s(-1) (given with 2 sigma statistical uncertainty). The temperature dependence of the reaction does not obey the Arrhenius law and it is described well by the two-exponential rate expression of k(2)(300-410 K) = 3.60 x 10(-3) exp(-10500/T) + 1.56 x 10(-13) exp(-910/T) cm(3) molecule(-1) s(-1). The rate coefficient of k(1) = (1.90 +/- 0.19) x 10(-13) cm(3) molecule(-1) s(-1) has been determined for the EtF-reaction at room temperature (T = 298 K). Microscopic mechanisms for the OH + CH3C(O)F reaction have also been studied theoretically using the ab initio CBS-QB3 and G4 methods. Variational transition state theory was employed to obtain rate coefficients for the OH + CH3C(O)F reaction as a function of temperature on the basis of the ab initio data. The calculated rate coefficients are in good agreement with the experimental data. It is revealed that the reaction takes place predominantly via the indirect H-abstraction mechanism involving H-bonded prereactive complexes and forming the nascent products of H2O and the CH2CFO radical. The non-Arrhenius behavior of the rate coefficient at temperatures below 500 K is ascribed to the significant tunneling effect of the in-the-plane H-abstraction dynamic bottleneck. The production of FC(O)OH + CH3 via the addition/elimination mechanism is hardly competitive due to the significant barriers along the reaction routes. Photochemical experiments of AcF were performed at 248 nm by using exciplex lasers. The total photodissociation quantum yield for CH3C(O)F has been found significantly less than unity; among the primary photochemical processes, C-C bond cleavage is by far dominating compared with CO-elimination. The absorption spectrum of AcF has also been determined by displaying a strong blue shift compared with the spectra of aliphatic carbonyls. Consequences of the results on atmospheric chemistry have been discussed

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes

Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1‘s pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3-promoter in response to Nell-1 treatment. By revealing the Nell-1 → Nfatc1 → Runx3→Ihh cascade, we demonstrate the involvement of Nfatc1, a nuclear factor of activated T-cells, in chondrogenesis, while providing innovative insights into developing a novel therapeutic strategy for cartilage regeneration and other chondrogenesis-related conditions. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

Fibromodulin Reduces Scar Size and Increases Scar Tensile Strength in Normal and Excessive-Mechanical-Loading Porcine Cutaneous Wounds

Hypertrophic scarring is a major postoperative complication which leads to severe disfigurement and dysfunction in patients and usually requires multiple surgical revisions due to its high recurrence rates. Excessive-mechanical-loading across wounds is an important initiator of hypertrophic scarring formation. In this study, we demonstrate that intradermal administration of a single extracellular matrix (ECM) molecule—fibromodulin (FMOD) protein—can significantly reduce scar size, increase tensile strength, and improve dermal collagen architecture organization in the normal and even excessive-mechanical-loading red Duroc pig wound models. Since pig skin is recognized by the Food and Drug Administration as the closest animal equivalent to human skin, and because red Duroc pigs show scarring that closely resembles human proliferative scarring and hypertrophic scarring, FMOD-based technologies hold high translational potential and applicability to human patients suffering from scarring—especially hypertrophic scarring. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine

Development of a hardware-in- loop simulation platform for NPP main control systems

The simulation technology of the nuclear power plant are gradually applying to the nuclear power industry. However, most of the research on nuclear power plant simulation system only focus on pure computerized simulation at present, and it is difficult to fully display the characteristics of the simulating objects. In order to simulate the response characteristics of control system more really, a hardware-in-loop simulation platform of main control systems in the nuclear power plant has been developed in this paper. This simulation platform consists of thermal-hydraulic model, control and protection system model, physical DCS system and real-time interactive database. A physical industrial DCS system has been coupled to this platform to simulate the main control systems in the NPP, which makes the simulation result much closer to the actual control systems. The devoloped simulation platform has been validated by some steady and transient cases in this paper. This hardware-in-loop simulation platform can be used in the simulation and optimal design of NPP control systems. Furthermore, it can be used in the failure mode and effect analysis of the instrumentation and control systems in the nuclear power plant

Global quasi-daily fractional vegetation cover estimated from the DSCOVR EPIC directional hotspot dataset

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