Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as “Beimu”, for the treatment of cough for thousands of ...years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3–6), and 19 known steroidal alkaloids (7–25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7–10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-β (TGF-β) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-β-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-β-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-β-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents.
Six undescribed and nineteen known cevanine-type alkaloids were isolated from the bulbs of Fritillaria unibracteata var. wabuensis and eight alkaloids exhibited antifibrotic activities in vitro. Display omitted
•25 cevanine-type alkaloids were isolated from Fritillaria unibracteata var. wabuensis.•The antifibrotic activities of steroidal alkaloids were evaluated for the first time.•Compounds 14 and 17 inhibited TGF-β-induced EMT in A549 cells.•Compounds 14 and 17 inhibited TGF-β-induced migration and proliferation of fibroblasts.
Nicotinamide phosphoribosyltransferase (NAMPT) maintains mitochondrial function and protects against cerebral ischemic injury by improving energy metabolism. Notoginsenoside R1 (R1), a unique ...constituent of Panax notoginseng, has been shown to promote the proliferation and tube formation of human umbilical vein endothelial cells. Whether R1 has proangiogenesis on the activation of NAMPT in ischemic stroke remains unclear. The purpose of this study was to investigate the pharmacodynamic effect and mechanism of R1 on angiogenesis after ischemic stroke. We used male Sprague-Dawley (SD) rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered via intraperitoneal (i.p.) injection immediately after ischemia induction. The promotion of R1 on angiogenesis were detected by immunofluorescence staining, 3D stereoscopic imaging and transmission electron microscopy detection. HBMEC cells were pretreated with different concentrations of R1 for 12 h before oxygen-glucose deprivation/reoxygenation (OGD/R) exposure. Afterward, scratch assay, EdU staining and tube formation were determined. Western blot analyses of proteins, including those involved in angiogenesis, NAMPT-SIRT1 cascade, VEGFR-2, and Notch signaling, were conducted. We showed that R1 significantly restored cerebral blood flow, improved mitochondrial energy metabolism and promoted angiogenesis. More importantly, incubation with 12.5–50 μM R1 significantly increased the migration, proliferation and tube formation of HBMECs in vitro. The promotion of R1 on angiogenesis were associated with the NAMPT-NAD+-SIRT1 cascade and Notch/VEGFR-2 signaling pathway, which was partially eliminated by inhibitors of NAMPT and SIRT1. We demonstrated that R1 promotes post-stroke angiogenesis via activating NAMPT-NAD+-SIRT1 cascade. The modulation of Notch signaling and VEGFR-2 contribute to the post-stroke angiogenesis. These findings offer insight for exploring new therapeutic strategies for neurorestoration via R1 treatment after ischemic stroke.
Schematic diagram of the mechanisms underlying the R1-induced promotion of angiogenesis after ischemia-reperfusion injury. Overall, R1 activates the NAMPT-NAD+-SIRT1 cascade, SIRT1 deacetylates NICD, which led to inhibition of DLL4-Notch signaling. Inhibition of the Dll4-Notch signaling pathway can upregulate the expression of VEGFR-2, thereby promoting angiogenesis after ischemia. Display omitted
•A new therapeutic strategy in the treatment of ischemic stroke was proposed.•The mechanism relies on the promotion of angiogenesis.•A new method for the detection of energy metabolic molecules were proposed.
Silicon carbide (SiC) vertical-diffused metal oxide field transistor (VDMOSFET) is an important power device for aerospace application. However, it is sensitive to heavy particles radiation in space ...which can cause catastrophic single-event effects (SEEs). In this article, a method of SEE hardening at a high linear energy transfer (LET) value range is studied to the 1.2 kV-rated SiC VDMOSFET by the 2-D numerical simulator SILVACO TCAD. Simulation results illustrate that, compared with the VDMOSFET which only has four buffer (FB-VDMOSFET) layers, the improved MOSFET could increase the abilities of single-event burnout (SEB) and the single-event gate rupture (SEGR) of the device effectively. At the same time, the proposed MOSFET has the lower specific ON-resistance (<inline-formula> <tex-math notation="LaTeX">{R}_{\text {on, sp}} </tex-math></inline-formula>) at room temperature. As a result, the gate oxide of the FB-VDMOSFET has reached 7.5 MV/cm and the maximum temperature reached 2480 K at a voltage of 600 V and an LET value of 0.5 pC/<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula>. However, the maximum temperature of the improved VDMOSFET is 2150 K when <inline-formula> <tex-math notation="LaTeX">{V}_{\mathrm {DS}} </tex-math></inline-formula> = 950 V.
This article proposes an RC -IGBT structure with N-Si/n-Ge heterojunction (NNH-IGBT) to suppress snapback effect. Because the proposed N-Si/n-Ge heterojunction acts as a gradually reverse bias diode ...to suppress the electron flow into the N-short region, so the snapback effect can be suppressed. For the same <inline-formula> <tex-math notation="LaTeX">{\mathrm{\scriptstyle {ON}}} </tex-math></inline-formula>-state voltage drop (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {CE}} </tex-math></inline-formula>), the turn-off loss (<inline-formula> <tex-math notation="LaTeX">{E}_{\mathrm{\scriptstyle {OFF}}} </tex-math></inline-formula>) of the NNH-IGBT is lower than the conventional RC -IGBT (Con- RC -IGBT). In addition, the reverse recovery speed of NNH-IGBT is nearly identical to the Con- RC -IGBT. Because of the use of heterojunction, the NNH-IGBT is suitable for operate to suppress the snapback effect, especially at low temperatures.
Spontaneous imbibition of water-based frac- turing fluids into the shale matrix is considered to be the main mechanism responsible for the high volume of water loss during the flowback period. ...Understanding the matrix imbibition capacity and rate helps to determine the frac- turing fluid volume, optimize the flowback design, and to analyze the influences on the production of shale gas. Imbibition experiments were conducted on shale samples from the Sichuan Basin, and some tight sandstone samples from the Ordos Basin. Tight volcanic samples from the Songliao Basin were also investigated for comparison. The effects of porosity, clay minerals, surfactants, and KC1 solutions on the matrix imbibition capacity and rate were systematically investigated. The results show that the imbibition characteristic of tight rocks can be characterized by the imbibition curve shape, the imbibition capacity, the imbibition rate, and the diffusion rate. The driving forces of water imbibition are the capillary pressure and the clay absorption force. For the tight rocks with low clay contents, the imbibition capacity and rate are positively correlated with the porosity. For tight rocks with high clay content, the type and content of clay minerals are the most impor- tant factors affecting the imbibition capacity. The imbibed water volume normalized by the porosity increases with an increasing total clay content. Smectite and illite/smectite tend to greatly enhance the water imbibition capacity. Furthermore, clay-rich tight rocks can imbibe a volume of water greater than their measured pore volume. The aver- age ratio of the imbibed water volume to the pore volume is approximately 1.1 in the Niutitang shale, 1.9 in the Lujiaping shale, 2.8 in the Longmaxi shale, and 4.0 in the Yingcheng volcanic rock, and this ratio can be regarded as a parameter that indicates the influence of clay. In addition, surfactants can change the imbibition capacity due to alteration of the capillary pressure and wettability. A 10 wt% KC1 solution can inhibit clay absorption to reduce the imbibition capacity.
With the enhancement in the functional integration of components and concentration on lightweight materials, complex sheet metal parts are widely used in automobile and aviation industrial clusters. ...Consequently, the sheet hydroforming process has become an attractive fabricating technology for forming lightweight materials and complicated products. In this research, the hydrodynamic deep drawing (HDD) process of a composite conical box with double concave cavities was investigated through theoretical analysis, numerical simulation, and process experimentation. Furthermore, the process window diagram (PWD) was calculated using the stress analytical model combining material properties with workpiece geometrical features. The influence of cavity pressure loading locus on the forming quality of the fabricated part and the deformation behavior of aluminum alloy was explored. The forming results indicated that the initial pressure, full pressure, and loading locus are the fundamental parameters directly related to the forming quality and dimensional accuracy. For the conical part with composite features, the reasonable initial pressure value is crucial for the thickness homogeneity of the double concave characteristics, whereas the magnitude of the full pressure is vital for improving the quality of the conical feature. In addition, the optimal loading locus of the cavity pressure is characterized by two turning points, which are related to the punch corner radius, die shoulder radius, blank thickness, and angle of the conical feature.
This brief presents 2-D numerical simulation results of a single-event burnout (SEB) in a 4H-silicon carbide (SiC) junction termination extension (JTE) termination structure of a power ...metal-oxide-semiconductor field-effect transistor (MOSFET). Using the rated 1.5-kV JTE termination structure, the most sensitive ion's strike position to SEB is proved to be the edge of the P + /P − JTE region. Due to the severe punchthrough of the electric field, the source contact region is found to the most sensitive region to induce an SEB event. The SEB performance of the JTE termination structure with a single buffer layer or multilayer buffer is evaluated. The results show that the electric field distribution in four buffer layers (FBLs) is the most uniform to achieve the best SEB performance. Therefore, by adding an optimal FBL design to the termination region, the SEB threshold voltage can be increased to 1210 V instead of the common structure's 250 V. The SEB safe operating area of the power MOSFET with an optimal FBL can increase more than three times compared with the common one.
In this article, the performance and triggering mechanism of the single-event burnout (SEB) of a 4H-SiC trench-gate (TG) MOSFET structure are evaluated by the 2-D numerical simulations. The novel N + ...island buffer 4H-SiC TG MOSFET and the conventional TG 4H-SiC MOSFET are analyzed and compared to examine whether an N + island region introduced in the second buffer can effectively reduce the impact ionization located at the N − drift/N + buffer junction and improve device tolerance to the SEB. The TCAD simulation results revealed that compared with the conventional structure, which is a simple double-buffer structure, the N + island buffer-hardened structure changed the burnout threshold voltage, improving the SEB performance significantly. In addition, the results proved that the impact ionization played an important role in the SEB triggering mechanism, significantly affecting the SEB performance of the 4H-SiC TG MOSFET. The performance of the hardened N + island buffer with a different dopant concentration of N-buffer 2 and a size of N + island is discussed. The specific burnout threshold voltage at the optimal parameters of the proposed structure is 47% higher than that of the conventional structure.
In this study, we have synthesised fluorescent liquid crystal polymers with good fluorescence and optical properties through effective molecular design. Firstly, two series of cholesteric liquid ...crystal polymers (PN and PS series) were prepared by graft copolymerisation of cholesteric monomer(N
1
), monomer containing cyanobiphenyls with different length of carbon-chain (N
2
and N
3
) and monomer containing bromine (6-Br) with polymethylhydrosiloxane chain as the polymer backbone. Secondly, we obtained fluorescent polymers RPN and RPS series by etherification reaction of PN and PS series with fluorescent monomer (F). The molecular structures and mesomorphic behaviour of monomers and polymers were characterised by usual ways. All the polymers are confirmed to consist with molecular design. The fluorescence of the polymers was investigated by fluorescence spectroscopy and fluorescent images. The fluorescence intensity of polymers is highly dependent on temperature. Fluorescent cholesteric liquid crystal polymers emitted different intensity fluorescence under ultraviolet irradiation and some regularities were summarised. RPN series with short carbon-chain meets our expectations for performance with dual effects of fluorescence and selective reflection, which were well verified. The effect of monomers with different chain lengths on the properties of fluorescent polymers has been described.
Fluorescent cholesteric liquid crystal polymers were synthesised with polymethylhydrogensiloxane as the main chain by hydrosilylation and etherification reaction, which seems a viable strategy for preparing such multifunction polymers.
The polymers of RPN series we synthesised are equipped with both selective reflection and fluorescence properties.
The selective reflection and fluorescence both have a characteristic of depending on temperature.
The fluorescent cholesteric liquid crystal polymers we synthesised presented lower glass transition temperature and higher isotropic transition temperature. In other words, it has a wide range of application.
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