AIM: To investigate the morphological changes of meibomian glands in patients with type 2 diabetes mellitus (DM).METHODS: Of 118 eyes (118 patients) with type 2 DM (DM group) and 100 eyes of 100 control subjec...AIM: To investigate the morphological changes of meibomian glands in patients with type 2 diabetes mellitus (DM).METHODS: Of 118 eyes (118 patients) with type 2 DM (DM group) and 100 eyes of 100 control subjects (control group) were enrolled. After completing an ocular surface disease index (OSDI) questionnaire, the non-invasive tear film break-up time (NI-BUT) and the structure of the meibomian glands (MGs, meibography) were assessed by the Keratograph 5M system. Partial or complete loss of MG was scored for each eyelid from grade 0 (no loss) to grade 3 (lost area was 〉2/3 of the total MG area), which were also examined by laser scanning confocal microscopy (LSCM). The primary outcomes were meibomian gland acinar unit density (MGAUD), meibomian gland acinar longest diameter (MGALD) and meibomian gland acinar shortest diameter (MGASD).RESULTS: Compared with control group, the OSDI was significantly higher in DM group (Z=-5.916; P〈0.001), while the NI-BUT was significantly lower (Z=-7.765; P〈0.001). Keratograph showed that there were more MGs dropout in DM group than that in control group. The meiboscore was significantly higher in DM group compared with control group (Z=-3.937; P〈0.001). LSCM revealed that there were cytological alterations of MGs in DM group compared with control group, which included enlargement of MG acinar units and decreased in density of MG acinar units. Specifically, there were lower MGAUD, larger MGALD and MGASD in DM group than control group (Z=-10.120, -9.4442, -7.771; P〈0.001).CONCLUSION: Compared with the normal control participants, the patients with type 2 DM had more unstable tear films and severe symptoms of dry eye. Using Keratograph 5M system and LSCM, we found that the patients with type 2 DM had more significant morphological and cytological changes and dysfunction in MGs.展开更多
With the aim of developing a low-cost and efficient visible-light-driven photocatalyst for radical polymerization,iron-chelating polyimide networks(Fe@MPI)was fabricated by firstly synthesizing photoactive melamine-co...With the aim of developing a low-cost and efficient visible-light-driven photocatalyst for radical polymerization,iron-chelating polyimide networks(Fe@MPI)was fabricated by firstly synthesizing photoactive melamine-containing polyimide(MPI)networks and then incorporating Fe(III)cations into the polymer networks.Fe@MPI exhibits a wide absorption spectrum ranging from 220 to 1250 nm and 3.5 times higher photocurrent intensity as compared with the pristine MPI.Based on its excellent photo-electric properties,Fe@MPI was employed as a recyclable heterogeneous catalyst,providing sufficient activity for the visible-light driven radical polymerization to synthesize poly(methyl methacrylate)with molecular weight up to 31.×10^4 g mol.Taking advantage of the heterogeneous nature of the catalyst,Fe@MPI could be facilely regenerated from the polymerization solution by filtration without an obvious loss of its activity.This research provides a novel recyclable catalyst for visible-light driven radical polymerization.展开更多
Terminalic acid 1, a new hydrolysable tannin, was isolated from the fruit of Terminalia chebula. Its structure was found to be 1-O-galloyl-2,4-chebuloyl-beta-D-glucopyranose by chemical method and H-1-NMR, C-13-NMR, H...Terminalic acid 1, a new hydrolysable tannin, was isolated from the fruit of Terminalia chebula. Its structure was found to be 1-O-galloyl-2,4-chebuloyl-beta-D-glucopyranose by chemical method and H-1-NMR, C-13-NMR, H-1-H-1 COSY, HMQC, HMBC and FAB-MS spectral analyses.展开更多
A comprehensive mathematical model was established and used to simulate the macro and microstructure evolution during the production process of 5CrNiMo steel ingot by electroslag remelting (ESR) method. Along the in...A comprehensive mathematical model was established and used to simulate the macro and microstructure evolution during the production process of 5CrNiMo steel ingot by electroslag remelting (ESR) method. Along the ingot height, the macrostructure distribution characteristics changed from vertical, fine columnar grains to tilted, coarse columnar grains, and this transformation process occurred at the very beginning of ESR. In the cross section of the ingot, there were three grain morphology regions and two grain type transition regions from the outside to the center of the ingot. These regions were the fine columnar grain region, columnar competitive growth transition re gion, coarse columnar grain region, columnar to equiaxed grain transition (CET) region, and coarse equiaxed grain region. The influence of the remelting rate on the macrostructure and mlcrostructure was investigated using a series of experiments and simulations. The results showed that a low remelting rate could produce a small grain growth angle (GGA) ; the average secondary dendrite arm spacing (SDAS) firstly decreased and then increased as the remelting rate increased. An excessively high or low remelting rate can increase the GGA and average SDAS in ingots. Thus, the remelting rate should be controlled within a suitable range to reduce composition microsegregation and microshrinkage in the ingot to produce an ESR ingot with satisfactory hot forging performance.展开更多
Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective the...Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective therapy has not yet been developed. In this study, we found that EGCG induced apoptosis in U251 glioma cells via the laminin receptor (molecular weight 67kDa) in a time- and dose-dependent manner, decreased their invasiveness and inhibited their proliferation. The mitogen-activated protein kinase pathway was shown to be involved in glioma cell apoptosis and proliferation. Furthermore, the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9 were reduced after EGCG treatment. These results suggest that EGCG has important therapeutic effects with low toxicity and side-effects, and could be used in cancer chemoprevention.展开更多
The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-...The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 pg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4E- BP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.展开更多
Objective Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of LoniceraeJaponicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely ...Objective Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of LoniceraeJaponicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely used in China for the treatment of viral infection, fever, and inflammation. To assess the potential interacting of RDN with co-administered drugs, the inhibitory effects of RDN on the enzyme activities (CYP1A1, CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2) of rat liver microsomes were investigated by a cocktail method. Methods A sensitive and specific LC-MS method capable of simultaneous quantification of five metabolites in rat liver microsomes was developed and validated. Then RDN (0.625%-1.0%) was incubated with rat liver microsomes and specific substrates. The enzyme activities were expressed as the formation rate of the specific metabolites of the substrates (pmol- mg. protein-1 . min-1). Results RDN competitively inhibited the activities of CYP1A2 and CYP2C11, with inhibition constant (/~) values determined to be 0.18% and 0.63%, respectively. RDN exhibited the mixed inhibition on the activity of CYP2D1, with a K1 value of 0.15%. The activities of CYP1A1 and CYP3A1/2 were not markedly inhibited even by 1.0% RDN. Conclusion RDN could inhibit the rat enzyme activities of CYP1A2, 2Cll, and 2D1 in vitro with different inhibition modes, which is worthy of promoting safety and efficacy of RDN.展开更多
Electroslag surfacing with liquid metal (ESSLM) is an excellent method for producing high quality bimetallic compound rollers. The quality of each compound roller is primarily determined by the metallurgical quality...Electroslag surfacing with liquid metal (ESSLM) is an excellent method for producing high quality bimetallic compound rollers. The quality of each compound roller is primarily determined by the metallurgical quality of the combined interface. A GCrl5/40Cr compound roller is produced using an ESSLM non-consumable electrode electro- slag heating method. The temperature and electric fields produced by the ESSLM system are calculated. As the roller core moves downward in the mold, it passes through five sections., the preheating section, the rapid heating section, the temperature homogenizing section, the bimetal fusing section and the cooling section which listed from the top to bottom of the mold, respectively. The temperature distribution and the degree of the surface temperature fluctuation in the roller core are different for each section. Near the combined interface, four layers are found from the roller core to the cladding layer= the remelting layer, the fusion layer, the interface solidification layer and the chilling layer, re spectively. Among these, the fusion and interface solidification layers are the key transition zones that greatly influ- ence the combination quality. The surface temperature of the roller core prior to cladding is mainly determined by the drawing velocity, and the thickness of the transition layer increases as the drawing velocity decreases. A transition layer that is too thick or too thin will reduce the mechanical properties at the combined interface. Therefore, the drawing velocity should be limited to a moderate range to produce a satisfactory bimetallic Compound roller.展开更多
Objective To study the in vitro antiproliferative effect and probable mechanism of solasonine on human breast cancer Bcap-37 cells, meanwhile, make comparison with solamargine. Methods The cytotoxicity was evaluated b...Objective To study the in vitro antiproliferative effect and probable mechanism of solasonine on human breast cancer Bcap-37 cells, meanwhile, make comparison with solamargine. Methods The cytotoxicity was evaluated by MTT assay. The cell damage and type of cell death were examined through Hoechst33342/PI and Annexin V/PI staining, respectively. Mitochondrial membrane potential was detected by JC-1 staining. The expression of Bcl-2, Bcl-x L, Bax, and cytochrome c was determined by immunoblot method, and the activation of caspase-3 was analyzed by immunocytochemistry method. Results Solasonine showed the different extents of cytotoxicity on eight human tumor cell lines as well as four human normal cell lines, and the IC50 values of solasonine ranged from 12.73 to 37.15 μmol/L. Cell apoptosis and mitochondria depolarization were observed in Bcap-37 cells after treatment with solasonine for 24 h, respectively. In immunoblot and immunocytochemistry analysis, solasonine obviously induced the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-x L, caused the release of cytochrome c from mitochondria into cytosol, and increased the expression of both pro- and cleaved caspase-3. Solamargine exhibited stronger antipoliferative activity than solasonine, but the similar mechanism in Bcap-37 cells in this study. Conclusion Solasonine possesses the antiproliferative effect on tumor cells. Regulation of the levels of Bcl-2, Bcl-x L, Bax, and activation of mitochondria cytochrome c-dependent apoptosis pathway might be one of its main antitumor mechanisms against breast cancer cells. In view of the cytotoxic effect of solasonine and solamargine also shown on normal cells, the safety needs concern when the antitumor activity is studied.展开更多
Objective In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods...Objective In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.展开更多
Swainsonine (1) belongs to the family of indolizine alkaloid with strong neurologically toxic effects on herbivorous livestock. Recently, a great amount of evidence confirmed that this alkaloid displayed a wide rang...Swainsonine (1) belongs to the family of indolizine alkaloid with strong neurologically toxic effects on herbivorous livestock. Recently, a great amount of evidence confirmed that this alkaloid displayed a wide range of bioactivities especially anti-cancer biological effects. The potential targets of swainsonine (1) were now revealed to be the mannosidase and Golgi mannosidase 1I. Its low yield in plants or fungi, and no economically total synthesis route in practice as the key bottleneck restricted its further structure- activities relationships (SAR) investigation in drug discovery. This mini-review highlighted the biosynthetic advance of swainsonine (1) from 1973 to 2017 based on the results of isotope-labelled experiments and the recent research of its biosynthetic gene cluster, which could provide some thoughts for further biosynthetic investigation and efficiently biomimetic synthesis of swainsonine (1) in order to increase its output in practice.展开更多
Objective To analyse the quantification of protopine from Corydalis Decumbentis Rhizoma(CDR)extract in brain tissues of rats.Methods A rapid,sensitive,and accurate analytical method based on rapid resolution liquid ...Objective To analyse the quantification of protopine from Corydalis Decumbentis Rhizoma(CDR)extract in brain tissues of rats.Methods A rapid,sensitive,and accurate analytical method based on rapid resolution liquid chromatography(RRLC)coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(Q-TOF-MS)was developed for the quantification of protopine in brain of rats.A simple liquid-liquid extraction process was employed for the sample preparation.Chromatographic separation was achieved using 1.8μm porous particle columns.Results The calibration curve of protopine was linear in the range of 12-897 ng/mL.The relative standard deviations of intra-and inter-day precision values were less than 10%.The extraction recoveries were 96.4%,99.6%,and 98.5%,for protopine at the concentration of 598.0,119.6,and 12.0 ng/mL,respectively,and internal standard(1.27μg/mL)was(98.60±0.02)%.Conclusion The validated method is successfully applied for the determination of protopine in brain tissue of rats after ig administration of CDR extract.展开更多
Bupivacaine ranks as the most potent and efficient drug among class I local anesthetics, but its high potential for toxic reactions severely limits its clinical use. Although bupivacaine-induced toxicity is mainly cau...Bupivacaine ranks as the most potent and efficient drug among class I local anesthetics, but its high potential for toxic reactions severely limits its clinical use. Although bupivacaine-induced toxicity is mainly caused by substantial blockade of voltage-gated sodium channels (VGSCs), how these hydrophobic molecules interact with the receptor sites to which they bind remains unclear. Navl.5 is the dominant isoform of VGSCs expressed in cardiac myocytes, and its dysfunction may be the cause of bupivacaine- triggered arrhythmia. Here, we investigated the effect of bupivacaine on Navl.5 within the clinical concentration range. The electrophysiological measurements on Navl.5 expressed in Xenopus oocytes showed that bupivacaine induced a voltage- and concentration-dependent blockade on the peak of/Na and the half-maximal inhibitory dose was 4.51 pmol/L. Consistent with other local anesthetics, bupivacaine also induced a use-dependent blockade on Navl.5 currents. The underlying mechanisms of this blockade may contribute to the fact that bupivacaine not only dose-dependently affected the gating kinetics of Nay1.5 but also accelerated the development of its open-state slow inactivation. These results extend our knowledge of the action of bupivacaine on cardiac sodium channels, and therefore contribute to the safer and more efficient clinical use of bupivacaine.展开更多
The paper focus on exploring new theoretical approach in education with development of online learning technology,from e-learning to u-learning and virtual reality technology,and points out possibilities such as const...The paper focus on exploring new theoretical approach in education with development of online learning technology,from e-learning to u-learning and virtual reality technology,and points out possibilities such as constructing a new teaching ecological system,ubiquitous educational awareness with ubiquitous technology,and changing the cognitive mode in learning process with virtual reality technology.Finally,the paper concerns effective approach to promote school-based teachers professional development through integrated ICT and classroom teaching.展开更多
Chaetoxanthone D(1), a new tetrahydropyran-substituted xanthone originated from polyketide pathway, together with the four known natural products chaetoxanthone C(2), alternariol methyl ether(3), alternariol(4...Chaetoxanthone D(1), a new tetrahydropyran-substituted xanthone originated from polyketide pathway, together with the four known natural products chaetoxanthone C(2), alternariol methyl ether(3), alternariol(4) and 2,5-dimethyl-7-hydroxychromone(5) was isolated from a strain of Chaetomium murorum. The structures of these compounds were elucidated based on extensive spectroscopic analyses. The absolute configurations of 1 and 2 were determined by using quantum chemical electronic circular dichroism(ECD) calculations.展开更多
Three new ent-kaurane diterpenoids fimbrialtols K–M(3–5) with highly substituted functionalities were isolated from the extract of Flickingeria fimbriata(B1.) Hawkes. The structures of these new compounds were d...Three new ent-kaurane diterpenoids fimbrialtols K–M(3–5) with highly substituted functionalities were isolated from the extract of Flickingeria fimbriata(B1.) Hawkes. The structures of these new compounds were determined by NMR and HR-ESIMS. The relative configurations of these compounds were determined by analysis of NOESY correlations. The absolute configurations of these new compounds were established by CD methods together with considering the biosynthetic pathway. Compounds 3 and4 contain a cinnamic carboxyl group, whereas compound 5 possesses a benzoic carboxyl group representing the first report in more than known 600 ent-kaurane diterpenoids.展开更多
文摘AIM: To investigate the morphological changes of meibomian glands in patients with type 2 diabetes mellitus (DM).METHODS: Of 118 eyes (118 patients) with type 2 DM (DM group) and 100 eyes of 100 control subjects (control group) were enrolled. After completing an ocular surface disease index (OSDI) questionnaire, the non-invasive tear film break-up time (NI-BUT) and the structure of the meibomian glands (MGs, meibography) were assessed by the Keratograph 5M system. Partial or complete loss of MG was scored for each eyelid from grade 0 (no loss) to grade 3 (lost area was 〉2/3 of the total MG area), which were also examined by laser scanning confocal microscopy (LSCM). The primary outcomes were meibomian gland acinar unit density (MGAUD), meibomian gland acinar longest diameter (MGALD) and meibomian gland acinar shortest diameter (MGASD).RESULTS: Compared with control group, the OSDI was significantly higher in DM group (Z=-5.916; P〈0.001), while the NI-BUT was significantly lower (Z=-7.765; P〈0.001). Keratograph showed that there were more MGs dropout in DM group than that in control group. The meiboscore was significantly higher in DM group compared with control group (Z=-3.937; P〈0.001). LSCM revealed that there were cytological alterations of MGs in DM group compared with control group, which included enlargement of MG acinar units and decreased in density of MG acinar units. Specifically, there were lower MGAUD, larger MGALD and MGASD in DM group than control group (Z=-10.120, -9.4442, -7.771; P〈0.001).CONCLUSION: Compared with the normal control participants, the patients with type 2 DM had more unstable tear films and severe symptoms of dry eye. Using Keratograph 5M system and LSCM, we found that the patients with type 2 DM had more significant morphological and cytological changes and dysfunction in MGs.
文摘With the aim of developing a low-cost and efficient visible-light-driven photocatalyst for radical polymerization,iron-chelating polyimide networks(Fe@MPI)was fabricated by firstly synthesizing photoactive melamine-containing polyimide(MPI)networks and then incorporating Fe(III)cations into the polymer networks.Fe@MPI exhibits a wide absorption spectrum ranging from 220 to 1250 nm and 3.5 times higher photocurrent intensity as compared with the pristine MPI.Based on its excellent photo-electric properties,Fe@MPI was employed as a recyclable heterogeneous catalyst,providing sufficient activity for the visible-light driven radical polymerization to synthesize poly(methyl methacrylate)with molecular weight up to 31.×10^4 g mol.Taking advantage of the heterogeneous nature of the catalyst,Fe@MPI could be facilely regenerated from the polymerization solution by filtration without an obvious loss of its activity.This research provides a novel recyclable catalyst for visible-light driven radical polymerization.
文摘Terminalic acid 1, a new hydrolysable tannin, was isolated from the fruit of Terminalia chebula. Its structure was found to be 1-O-galloyl-2,4-chebuloyl-beta-D-glucopyranose by chemical method and H-1-NMR, C-13-NMR, H-1-H-1 COSY, HMQC, HMBC and FAB-MS spectral analyses.
基金Item Sponsored by National Natural Science Foundation of China(51165030)
文摘A comprehensive mathematical model was established and used to simulate the macro and microstructure evolution during the production process of 5CrNiMo steel ingot by electroslag remelting (ESR) method. Along the ingot height, the macrostructure distribution characteristics changed from vertical, fine columnar grains to tilted, coarse columnar grains, and this transformation process occurred at the very beginning of ESR. In the cross section of the ingot, there were three grain morphology regions and two grain type transition regions from the outside to the center of the ingot. These regions were the fine columnar grain region, columnar competitive growth transition re gion, coarse columnar grain region, columnar to equiaxed grain transition (CET) region, and coarse equiaxed grain region. The influence of the remelting rate on the macrostructure and mlcrostructure was investigated using a series of experiments and simulations. The results showed that a low remelting rate could produce a small grain growth angle (GGA) ; the average secondary dendrite arm spacing (SDAS) firstly decreased and then increased as the remelting rate increased. An excessively high or low remelting rate can increase the GGA and average SDAS in ingots. Thus, the remelting rate should be controlled within a suitable range to reduce composition microsegregation and microshrinkage in the ingot to produce an ESR ingot with satisfactory hot forging performance.
基金supported by the Innovation Program of the Shanghai Municipal Education Commission(12ZZ100)the Natural Science Foundation of Shanghai Municipality+5 种基金China(10ZR1410800)the Leading Academic Discipline Project of Shanghai Municipal Education Commission‘Molecular Physiology’the Foundation for the University Scientific Selection and Cultivation for Excellent Youth Scholars of Shanghai MunicipalityChinathe National Basic Research Development Program of China(2010CB529806)
文摘Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective therapy has not yet been developed. In this study, we found that EGCG induced apoptosis in U251 glioma cells via the laminin receptor (molecular weight 67kDa) in a time- and dose-dependent manner, decreased their invasiveness and inhibited their proliferation. The mitogen-activated protein kinase pathway was shown to be involved in glioma cell apoptosis and proliferation. Furthermore, the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9 were reduced after EGCG treatment. These results suggest that EGCG has important therapeutic effects with low toxicity and side-effects, and could be used in cancer chemoprevention.
基金supported by grants from the National Basic Research Development Program of China(2010CB529806)the National Natural Science Foundation of China(31171064)+2 种基金the Shanghai Science and Technology CommissionChina(11JC140430010411956700 and 124119b0600)
文摘The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 pg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4E- BP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.
基金National Science and Technology Major Project“Creation of Major New Drugs”from China(No.2013ZX09402203)Natural Science Foundation of Jiangsu Province(No.BK2013403)
文摘Objective Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of LoniceraeJaponicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely used in China for the treatment of viral infection, fever, and inflammation. To assess the potential interacting of RDN with co-administered drugs, the inhibitory effects of RDN on the enzyme activities (CYP1A1, CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2) of rat liver microsomes were investigated by a cocktail method. Methods A sensitive and specific LC-MS method capable of simultaneous quantification of five metabolites in rat liver microsomes was developed and validated. Then RDN (0.625%-1.0%) was incubated with rat liver microsomes and specific substrates. The enzyme activities were expressed as the formation rate of the specific metabolites of the substrates (pmol- mg. protein-1 . min-1). Results RDN competitively inhibited the activities of CYP1A2 and CYP2C11, with inhibition constant (/~) values determined to be 0.18% and 0.63%, respectively. RDN exhibited the mixed inhibition on the activity of CYP2D1, with a K1 value of 0.15%. The activities of CYP1A1 and CYP3A1/2 were not markedly inhibited even by 1.0% RDN. Conclusion RDN could inhibit the rat enzyme activities of CYP1A2, 2Cll, and 2D1 in vitro with different inhibition modes, which is worthy of promoting safety and efficacy of RDN.
基金Item Sponsored by National Natural Science Foundation of China(51165030)
文摘Electroslag surfacing with liquid metal (ESSLM) is an excellent method for producing high quality bimetallic compound rollers. The quality of each compound roller is primarily determined by the metallurgical quality of the combined interface. A GCrl5/40Cr compound roller is produced using an ESSLM non-consumable electrode electro- slag heating method. The temperature and electric fields produced by the ESSLM system are calculated. As the roller core moves downward in the mold, it passes through five sections., the preheating section, the rapid heating section, the temperature homogenizing section, the bimetal fusing section and the cooling section which listed from the top to bottom of the mold, respectively. The temperature distribution and the degree of the surface temperature fluctuation in the roller core are different for each section. Near the combined interface, four layers are found from the roller core to the cladding layer= the remelting layer, the fusion layer, the interface solidification layer and the chilling layer, re spectively. Among these, the fusion and interface solidification layers are the key transition zones that greatly influ- ence the combination quality. The surface temperature of the roller core prior to cladding is mainly determined by the drawing velocity, and the thickness of the transition layer increases as the drawing velocity decreases. A transition layer that is too thick or too thin will reduce the mechanical properties at the combined interface. Therefore, the drawing velocity should be limited to a moderate range to produce a satisfactory bimetallic Compound roller.
基金Science and Technology Office of Jiangsu Province,and National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2013ZX09402203)
文摘Objective To study the in vitro antiproliferative effect and probable mechanism of solasonine on human breast cancer Bcap-37 cells, meanwhile, make comparison with solamargine. Methods The cytotoxicity was evaluated by MTT assay. The cell damage and type of cell death were examined through Hoechst33342/PI and Annexin V/PI staining, respectively. Mitochondrial membrane potential was detected by JC-1 staining. The expression of Bcl-2, Bcl-x L, Bax, and cytochrome c was determined by immunoblot method, and the activation of caspase-3 was analyzed by immunocytochemistry method. Results Solasonine showed the different extents of cytotoxicity on eight human tumor cell lines as well as four human normal cell lines, and the IC50 values of solasonine ranged from 12.73 to 37.15 μmol/L. Cell apoptosis and mitochondria depolarization were observed in Bcap-37 cells after treatment with solasonine for 24 h, respectively. In immunoblot and immunocytochemistry analysis, solasonine obviously induced the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-x L, caused the release of cytochrome c from mitochondria into cytosol, and increased the expression of both pro- and cleaved caspase-3. Solamargine exhibited stronger antipoliferative activity than solasonine, but the similar mechanism in Bcap-37 cells in this study. Conclusion Solasonine possesses the antiproliferative effect on tumor cells. Regulation of the levels of Bcl-2, Bcl-x L, Bax, and activation of mitochondria cytochrome c-dependent apoptosis pathway might be one of its main antitumor mechanisms against breast cancer cells. In view of the cytotoxic effect of solasonine and solamargine also shown on normal cells, the safety needs concern when the antitumor activity is studied.
基金supported by grants from the National Basic Research Development Program of China (2010CB529806)the National Natural Science Foundation of China (31171064)+1 种基金the Key Research Program of Science and Technology Commissions of Shanghai Municipality (11JC1404300)the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50108)
文摘Objective In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.
基金financial support from the National Natural Science Foundation of China(No. 31570340, for G. Ding)The National Key Research and Development Program of China (No. 2017ZX09101003-006-006)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Agricultural Sciences(No.502-17)
文摘Swainsonine (1) belongs to the family of indolizine alkaloid with strong neurologically toxic effects on herbivorous livestock. Recently, a great amount of evidence confirmed that this alkaloid displayed a wide range of bioactivities especially anti-cancer biological effects. The potential targets of swainsonine (1) were now revealed to be the mannosidase and Golgi mannosidase 1I. Its low yield in plants or fungi, and no economically total synthesis route in practice as the key bottleneck restricted its further structure- activities relationships (SAR) investigation in drug discovery. This mini-review highlighted the biosynthetic advance of swainsonine (1) from 1973 to 2017 based on the results of isotope-labelled experiments and the recent research of its biosynthetic gene cluster, which could provide some thoughts for further biosynthetic investigation and efficiently biomimetic synthesis of swainsonine (1) in order to increase its output in practice.
基金National Science and Technology Major Project"Creation of Major New Drugs"from China(2011ZX09401-097)
文摘Objective To analyse the quantification of protopine from Corydalis Decumbentis Rhizoma(CDR)extract in brain tissues of rats.Methods A rapid,sensitive,and accurate analytical method based on rapid resolution liquid chromatography(RRLC)coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(Q-TOF-MS)was developed for the quantification of protopine in brain of rats.A simple liquid-liquid extraction process was employed for the sample preparation.Chromatographic separation was achieved using 1.8μm porous particle columns.Results The calibration curve of protopine was linear in the range of 12-897 ng/mL.The relative standard deviations of intra-and inter-day precision values were less than 10%.The extraction recoveries were 96.4%,99.6%,and 98.5%,for protopine at the concentration of 598.0,119.6,and 12.0 ng/mL,respectively,and internal standard(1.27μg/mL)was(98.60±0.02)%.Conclusion The validated method is successfully applied for the determination of protopine in brain tissue of rats after ig administration of CDR extract.
基金supported by grants from the National Natural Science Foundation of China (31171064)the Key Research Program of Science and Technology Commissions of Shanghai Municipality (11JC1404300,13DJ1400300)with financial support from Xinhua Hospital (Chongming),Shanghai Jiaotong University School of Medicine
文摘Bupivacaine ranks as the most potent and efficient drug among class I local anesthetics, but its high potential for toxic reactions severely limits its clinical use. Although bupivacaine-induced toxicity is mainly caused by substantial blockade of voltage-gated sodium channels (VGSCs), how these hydrophobic molecules interact with the receptor sites to which they bind remains unclear. Navl.5 is the dominant isoform of VGSCs expressed in cardiac myocytes, and its dysfunction may be the cause of bupivacaine- triggered arrhythmia. Here, we investigated the effect of bupivacaine on Navl.5 within the clinical concentration range. The electrophysiological measurements on Navl.5 expressed in Xenopus oocytes showed that bupivacaine induced a voltage- and concentration-dependent blockade on the peak of/Na and the half-maximal inhibitory dose was 4.51 pmol/L. Consistent with other local anesthetics, bupivacaine also induced a use-dependent blockade on Navl.5 currents. The underlying mechanisms of this blockade may contribute to the fact that bupivacaine not only dose-dependently affected the gating kinetics of Nay1.5 but also accelerated the development of its open-state slow inactivation. These results extend our knowledge of the action of bupivacaine on cardiac sodium channels, and therefore contribute to the safer and more efficient clinical use of bupivacaine.
文摘The paper focus on exploring new theoretical approach in education with development of online learning technology,from e-learning to u-learning and virtual reality technology,and points out possibilities such as constructing a new teaching ecological system,ubiquitous educational awareness with ubiquitous technology,and changing the cognitive mode in learning process with virtual reality technology.Finally,the paper concerns effective approach to promote school-based teachers professional development through integrated ICT and classroom teaching.
基金financial support from Program for Innovative Research Team in IMPLAD(PIRTI)the Open Funding Project of the State Key Laboratory of Bioactive Substance and Function of Natural Medicines+1 种基金PUMC Youth Fund and the Fundamental Research Funds for the Central Universitiesthe Chinese National S&T Special Project on Major New Drug Innovation(Nos.2013ZX09508104,2011ZX09307-002-01)
文摘Chaetoxanthone D(1), a new tetrahydropyran-substituted xanthone originated from polyketide pathway, together with the four known natural products chaetoxanthone C(2), alternariol methyl ether(3), alternariol(4) and 2,5-dimethyl-7-hydroxychromone(5) was isolated from a strain of Chaetomium murorum. The structures of these compounds were elucidated based on extensive spectroscopic analyses. The absolute configurations of 1 and 2 were determined by using quantum chemical electronic circular dichroism(ECD) calculations.
基金financially supported by the Chinese National S&T Special Project on Major New Drug Innovation(No.2013ZX09508104)the Fundamental Research Funds for the Central Scientific Research Institutes for Public WelfareCAMS Innovation Fund for Medical Sciences(CIFMS,No.2016-I2M-3-015)
文摘Three new ent-kaurane diterpenoids fimbrialtols K–M(3–5) with highly substituted functionalities were isolated from the extract of Flickingeria fimbriata(B1.) Hawkes. The structures of these new compounds were determined by NMR and HR-ESIMS. The relative configurations of these compounds were determined by analysis of NOESY correlations. The absolute configurations of these new compounds were established by CD methods together with considering the biosynthetic pathway. Compounds 3 and4 contain a cinnamic carboxyl group, whereas compound 5 possesses a benzoic carboxyl group representing the first report in more than known 600 ent-kaurane diterpenoids.