A Pair of New Spirocyclic Alkaloid Enantiomers with TrxR Inhibitory Activities Were Isolated from Marine-Derived Aspergillus ruber TX-M4-1

One new spirocyclic alkaloid,5-isopentenyl-cryptoechinuline D(1),along with 11 known compounds(2–12),were iso-lated from a marine fungus Aspergillus ruber TX-M4-1.The structures of compounds 1–12 were elucidated by spectroscopic evi-dences.Compound 1 was initially isolated as an enantiomer,and further separation of 1 by chiral HPLC afforded a pair of enantio-mers,including(-)-5-isopentenyl-cryptoechinuline D(1a)and(+)-5-isopentenyl-cryptoechinuline D(1b).Their absolute configura-tions were elucidated by ECD spectroscopic data.Compounds 1a,5 and 10 could inhibit thioredoxin reductase(TrxR)activity with IC50 values of 6.2,36.3 and 18.6μmol L^(-1),respectively.Surface plasmon resonance(SPR)study also demonsrated the interactions between compounds 6,8 and Niemann-Pick C1 Like 1(NPC1L1)respectively,which indicate that compounds 6 and 8 are potential NPC1L1 inhibitors.

18β-glycyrrhetinic acid promotes gastric cancer cell autophagy and inhibits proliferation by regulating miR-328-3p/signal transducer and activator of transcription 3

BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.

Synthesis and Antitumor Activity of 3-[2-(4-Hydroxy-Phenyl)-Ethyl]-Benzo[d] Isoxazole-4,6-Diol

A new phloretin derivative 1 3-[2-(4-hydroxy-phenyl)-ethyl]-benzo[d] isoxazole-4,6-diol (yield 63%) was synthesized from phloretin by carbonyl nucleophilic addition condensation reaction. Its structure was characterized by 1H NMR, 13C NMR and HR-MS. The phloretin, compound 1, resveratrol and acetylated resveratrol were determined by comparing them with paclitaxel. Anti-tumor activity of alcohol on SPC-A1, EC109, A549, MCF-7 and MDA-MB-231 cell lines. Compound 1 showed better antitumor activity than docetaxel against A549 tumor cells.

Fixed-Bed Column Adsorption Modeling of MnO4- Ions from Acidic Aqueous Solutions on Activated Carbons Prepared with the Biomass

Activated carbons calcined at 400˚C and 600˚C (AC-400 and AC-600), prepared using palm nuts, collected in the town of Franceville in Gabon, were used to study the dynamic adsorption of MnO4- ions in acidic media on fixed bed column and on the kinetic modeling of experimental data of breakthrough curves of MnO4- ions obtained. Results on the adsorption of MnO4- ions in fixed-bed dynamics obtained on AC-400 and AC-600 adsorbents beds indicated that the AC-400 bed appears to be the most efficient in removing MnO4- ions in acidic media. Indeed, the adsorbed amounts, the adsorbed capacities at saturation and the elimination percentage of MnO4- ions obtained with AC-400 (31.24 mg;52.06 mg·g-1 and 41.65% respectively) were higher compared to those obtained with AC-600 (9.87 mg;16.45 mg·g-1 and 17.79% respectively). The breakthrough curves kinetic modeling revealed that the Thomas model and the pseudo-first-order kinetic model were the most suitable models to describe the adsorption of MnO4- ions on adsorbents studied in our experimental conditions. The results of the intraparticle diffusion model showed that intraparticle diffusion was involved in the adsorption mechanism of MnO4- ions on investigated adsorbents and was not the limiting step and the only process controlling MnO4- ions adsorption. In contrast to AC-400, the intraparticle diffusion on AC-600 bed plays an important role in the adsorption mechanism of MnO4- ions.

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Do Radio-loud Active Galactic Nuclei really follow the same M_(BH)-σ_* Relation as Normal Galaxies?

In an examination of the relationship between the black hole mass MBH and stellar velocity dispersion σ＊ in radio-loud active galactic nuclei （AGNs）, we studied two effects which may cause uncertainties in the black hole mass estimates of radio-loud AGNs： the relativistic beaming effect on the observed optical continuum radiation and the orientation effect on the broad emission line width. After correcting these two effects, we re-examined the MBH- σ[OIII] relation for a sample of radio-loud and radio-quiet AGNs, and found the relation for radio-loud AGNs still deviated from that for nearby normal galaxies and radio-quiet AGNs. We also found there is no significant correlation between radio jet power and narrow [OIII] line width, indicating absence of strong interaction between radio jet and narrow line region. It may be that the deviation of the MBH-σ＊ relation of radio-loud AGNs is intrinsic, or that the [OIII] line width is not a good indicator of σ＊ for radio-loud AGNs.

Disk-Corona Model in Active Galactic Nuclei: an Observational Test

We compiled a sample of 98 radio-quiet active galactic nuclei observed by ASCA, Chandra, XMM-Newton, INTEGRAL and Swift with the aim of testing the formation of hot corona and the magnetic shear stress operating in a disk-corona system. We found a strong correlation between the hard X-ray luminosity, bolometric luminosity LBol and Eddington luminosity LEdd, in the sense that the fraction f of hard X-ray to the bolometric luminosity is inversely proportional to the Eddington ratio. This correlation favors the shear stress tensor being of the form of trФ∝ Pgas, with which the disk-corona structure is stable.

A NEW OPTICALLY ACTIVE POLYURETHANE DERIVED FROM CHIRAL(2R,3R)(+)-DIETHYL L-TARTRATE AND DIISOCYANATE

Optically active polyurethane was synthesized by the polyaddition of (2R, 3R)-(+)-diethyl L-tartrate (DET), 4,4'-diphenylmethane diisocyanate (MDI) and polyethylene glycol (PEG) with various molecular weights at 60 degrees C in DMSO. The polymers were characterized by specific rotation, DSC and H-1 NMR spectra.

调肝止血中药对置Cu-IUD大鼠外周血清及子宫组织t-PA,PAI活性的影响

目的:观察调肝止血中药柴胡止血液对置含铜宫内节育器(Cu-IUD)大鼠子宫局部及外周血清纤溶状态的影响,探讨调肝止血中药治疗置Cu-IUD后子宫异常出血的机理。方法:采用发色底物法测定了柴胡止血液对置Cu-IUD大鼠子宫组织及外周血清中组织型纤溶酶原激活物(t-PA)及其抑制剂(PAI)活性的影响。结果:与正常对照比较,置Cu-IUD后大鼠子宫组织t-PA活性明显升高,PAI活性也代偿性小幅度升高,t-PA/PAI比值明显高于正常对照组:使用柴胡止血液治疗后,t-PA活性及t-PA/PAI比值较模型对照组明显降低。同时,模型组t-PA活及t-PA/PAI比值较正常对照组有所升高,而PAI活性无明显变化,经柴胡止血液治疗后,t-PA、PAI活性及t-PA/PAI比值恢复正常。结论:置Cu-IUD大鼠子宫局部纤维系统功能亢进,其全身纤溶系统功能也有一定升高,调肝止血中药柴胡止血液对置Cu-IUD后大鼠子宫组织及外周血清纤溶状态有一定调整作用,能明显降低t-PA活性及t-PA/PAI比值,这是其有效治疗置Cu-IUD后子宫异常出血的作用机理之一。

置MA-IUD妇女经血纤溶抗凝血及凝血因子的变化

本文以Tcu220c-IUD为对照,测定置MA-IUD妇女月经总量;经血纤溶系统包括组织型纤溶酶原激活剂(t-PA)活性、纤溶酶原(PLG)含量和纤溶活性(Fa);经血抗凝血物质包括抗凝血酶-Ⅲ(AT-Ⅲ)活性、蛋白 C(PC)抗原含量和 PC 活性以及经血凝血因子包括因子Ⅶ相关抗原(ⅧR:Ag)和纤维蛋白原(Fg)含量。实验表明 MA-IUD 能使妇女月经量明显减少,其与宫腔局部纤溶活性和抗凝血系统活性下降有关。宫腔局部凝血因子无明显改变,IUD 之孕激素的局部释放对肝脏无影响。

S-2251底物显色法测定放置IUD后妇女子宫内膜组织纤溶酶原激活物(t-PA)活性

本文采用敏感性高,特异性强和重复性好的S-2251底物显色法对37例放置金属单环后月经量过多、经量正常和未放器经量正常妇女的子宫内膜进行t-PA活性测定。结果表明放器后经量过多者子宫内膜组织纤溶酶原激活物(t-PA)活性明显高于放器后经量正常和未放器者,但后两组之间的差别在统计学上无显著性意义。带器妇女的经量与t-PA活性之间存在正相关性。本文提示,只有放器后经量增多者子宫内膜t-PA活性才增加;虽放器但经量正常者,其t-PA活性并不增加。

Efficient electroreduction of nitrate via enriched active phases on copper-cobalt oxides

Electrochemical conversion of nitrate(NO_(3)~-) to ammonia(NH_(3)) can target two birds with one stone well, in NO_(3)^(-)-containing sewage remediation and sustainable NH_(3) production. However, single metalbased catalysts are difficult to drive high-efficient NO_(3)~- removal due to the multi-electron transfer steps.Herein, we present a tandem catalyst with simple structure, Cu-Co binary metal oxides(Cu-Co-O), by engineering intermediate phases as catalytic active species for NO_(3)~- conversion. Electrochemical evaluation,X-ray photoelectron spectroscopy, and in situ Raman spectra together suggest that the newly-generated Cu-based phases was prone to NO_(3)~- to NO_(2)~- conversion, then NO_(2)~- was reduced to NH_(3) on Co-based species. At an applied potential of -1.1 V vs. saturated calomel electrode, the Cu-Co-O catalyst achieved NO_(3)~- -N removal of 90% and NH_(3) faradaic efficiency of 81% for 120 min in 100 m L of 50 mg/L NO_(3)~- -N,consuming only 0.69 k Wh/mol in a two-electrode system. This study provides a facile and efficient engineering strategy for developing high-performance catalysts for electrocatalytic nitrate conversion.

Activity of the Fungicide JS399-19 Against Fusarium Head Blight of Wheat and the Risk of Resistance

This report reviews the characteristics of JS399-19, a novel cyanoacrylate fungicide. JS399-19 strongly inhibits the mycelial growth of the fungal plant pathogens of the genus Fusarium and exhibits great potential in controlling Fusarium head blight （FHB） on wheat and other cereals. The mode of action of JS399-19 is evidently different from that of benzimidazole （for example, carbendazim） and other sort of fungicides, making it a possible replacement for carbendazim in China to manage carbendazim-resistant subpopulations of Fusarium graminearum and F. asiaticum. JS399-t9 has excellent protective and curative activity against these pathogens. Incorrect use of this fungicide, however, is likely to select for resistance. Among JS399-19-resistant mutants of F. asiaticum induced in the laboratory, the resistant level of mutants was high and the phenotype of resistance against JS399-19 was conferred by a major gene by genetic analysis. The fitness of laboratory-induced JS399-19-resistant mutants of F. asiaticum was nearly equal to that of their parents. JS399-19 lacks cross resistance with other sort fungicides. To control FHB with JS399-19 and to delay the development of the fungicide-resistance, farmers should use tank mixtures containing JS399-19 and carbendazim, metconazole, tebuconazole, or prothioconazole.

Statistics of Superluminal Motion in Active Galactic Nuclei

We have collected an up-to-date sample of 123 superluminal sources （84 quasars, 27 BL Lac objects and 12 galaxies） and calculated the apparent velocities （βapp） for 224 components in the sources with the A-CDM model. We checked the relationships between their proper motions, redshifts,βapp and 5 GHz flux densities. Our analysis shows that the radio emission is strongly boosted by the Doppler effect. The superluminal motion and the relativistic beaming boosting effect are, to some extent, the same in active galactic nuclei.

Calculation of Activity Coefficients for Components in Ti-15-3 Melt

Based on Kohler’s ternary solution model and Miedemaa’s model for calculating the heats of formation-△Hij of binary Systems, the integral equation has ben established for calculating the activity coefficients in ternarysolution. With the equation, the activity coefficients in Ti-15-3 melt have been calculated. The results show that allof components’ activity coefficients are less than 1, in other wolds, compared with ideal solution, all components takeon a negative deviation. At 2000K, the activity coefficients in Ti-15-3 melt are shown as: about 0.9 for Ti, about0.85 for V, about 0. 1 for Al, aboaut 0.5 for Cr and about 0.23 for Sn. me addition of V lowers the activity coefficient of Ti, but raise the ones of Al, Cr and Sn. These results can be directly used to calculate the evaporation loss ofAl, Cr and Sn during the ISM(Induction Skull Melting) process and at the same time estimate the reactivity betweenTi-15-3 melt and refractory during the cast production.

Semiannual velocity variations around the 2008 M_w 7.9 Wenchuan Earthquake fault zone revealed by ambient noise and ACROSS active source data

We continuously monitor the long-term seismic velocity variation of one of the major ruptured faults of the devastating 2008 Mw7.9 Wenchuan earthquake in China from July 2009 to January 2012,jointly using accurately controlled routinely operated signal system active source and seismic noise-based monitoring technique.Our measurements show that the temporal velocity change is not homogeneous and highly localized in the damaged fault zone and the adjacent areas.Velocity variations from the active and passive methods are quite consistent,which both are characterized by ±0.2 % seasonal variation,with peak and trough at winter and summer,respectively.The periodic velocity variation within fault zone exhibits remarkably positive correlation with barometric pressure with stress sensitivity in the order of 10-6Pa-1,suggesting that the plausible mechanism might be the crack density variation of the shallow subsurface medium of the damaged fault zone in response to the cyclic barometric pressure loading.

STRUCTURE,MOLECULAR WEIGHT AND BIOACTIVITIES OF(1→3)-β-D-GLUCANS AND ITS SULFATED DERIVATIVES FROM FOUR KINDS OF LENTINUS EDODES

Lentinan samples,(1→3)-β-D-glucans containing 4.6-15.2 wt% proteins,coded as L-I_1 L-I_2 L-I_3 and L-I_4(L-I)were isolated from four kinds of Lentinus edodes.These glucans were treated with acetone to remove the protein in orderto obtain free protein glucans coded as LNP-I_1,LNP-I_2.LNP-I_3 and LNP-I_4(LNP-I).The free-protein polysaccharideswere sulfated to give derivatives(S-LNP-I)with degree of substitution(DS)from 0.4-0.8.The structural features andweight-average molecular weight(M_w)of the samples were investigated by using infrared spectroscopy,elemental analysis,^(13)C-NMR,size exclusion chromatography combined with laser light scattering(SEC-LLS)and viscometry.The effects ofstructure and conformation of the polysaccharides on antitumor activities were assayed in vivo(Sarcoma 180 solid tumors)and in vitro(Sarcoma 180,HL-60,MCF-7 and Vero tumors).The results indicated that the predominant species of thesamples L-I and LNP-I in 0.2 mol/L NaCl aqueous solution existed as triple-helical chains with high rigidity and in dimethylsulfoxide(DMSO)as single-flexible chains.Interestingly,the antitumor activities of LNP-I are lower than those of the nativeglucans(L-I),whereas their sulfated derivatives have higher inhibition ratio against Sarcoma 180 than LNP-I.The resultsreveal that the binding of protein,sulfated modification and the triple helix conformation are important factors in theenhancement of the antitumor activities of polysaccharides on the whole.

Characterization and Anti-tumor Activity of Glycopeptides from Ganoderma sinensis

The water-soluble part（GS） of Ganoderma sinense Zhao, Xu et Zhang was divided into high molecular（GS-H） and low molecular（GS-L） parts by Cellulose Super Filtration, and GS was also fractionated into four fractions, GS-1, 2, 3, and 4 by ethanol precipitation according to their molecular weights. Chemical analysis shows that GS and GS-1, 2, 3, 4 were complexes of polysaccharide and peptide. The fractions with molecular weights over 4000, GS-1, 2, 3, and GS-H show anti-tumor activities, however, the fractions with molecular weights lower than 4000, GS-4, and GS-L have no anti-tumor activity, indicating that the anti-tumor activity of Ganoderma Sinensis was caused by glucopeptides with molecular weight ranging from 4000 to 20000. Two purified glucopeptides, GS-6b and GS-7b were obtained from GS-H by ion-exchange and gel-permeation chromatography. Their molecular weights, glycosidic linkages, and configurations were detected by means of IR spectrum, sugar composition analysis, and methylation analysis. The polysaccharide parts of GS-6b and GS-7b had glucan backbone consisting of β-1→3 Glc, and side chain containing glucosyl, mannosyl, fucosyl, xylosyl, galactosyl, and glucuronic acid residues attached on 1-2, 1-4, 1-6 positions of the backbone of GS-6b, or 1-6, 1-4 positions of the backbone of GS-7b. The peptide parts in GS-6b and GS-7b were composed of 10 kinds of amino acids, including Asp, Ser, Arg, Gly, Thr, Pro, Ala, Val, Met, and Lys.

Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.