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Maintaining the effects of nematode-trapping fungi (NTF) agents in order to control plant-parasitic nematodes (PPNs) in different ecological environments has been a major challenge in biological control applications. To achieve such an objective, it is important to understand how populations of the biocontrol agent NTF are geographically and ecologically structured. A previous study reported evidence for ecological adaptation in the model NTF species Arthrobotrys oligospora. However, their large-scale geographic structure, patterns of gene flow, their potential phenotypic diversification, and host specialization remain largely unknown. In this study, we developed a new panel of 20 polymorphic short tandem repeat (STR) markers and analyzed 239 isolates of A. oligospora from 19 geographic populations in China. In addition, DNA sequences at six nuclear gene loci and strain mating types (MAT) were obtained for these strains. Our analyses suggest historical divergence within the A. oligospora population in China. The genetically differentiated populations also showed phenotypic differences that may be related to their ecological adaptations. Interestingly, our analyses identified evidence for recent dispersion and hybridization among the historically subdivided geographic populations in nature. Together, our results indicate a changing population structure of A. oligospora in China and that care must be taken in selecting the appropriate strains as biocontrol agents that can effectively reproduce in agriculture soil while maintaining their nematode-trapping ability.

Atmospheric aerosol pollution has seriously affected the ecological environment and human health in recent years. There are great differences in aerosol optical properties and types due to the influence of environmental conditions, meteorology, industrial and agricultural activities, and other factors of each ecological functional zones. Using MODIS aerosol products (including MCD19A2 and MOD04_3K), this study discussed the temporal and spatial distribution of aerosol optical depth (AOD), Ångström wavelength index (AE) and aerosol types in the Beijing–Tianjin–Hebei region (BTH region) based on the ecological functional zones from 2015 to 2020. The results showed as follows: (1) The AOD in BTH region showed an obviously spatial pattern of low in the north and high in the south, while the spatial pattern of AE was opposite to that of AOD. In addition, the dominant aerosol type of the north part was clean aerosol, the dominant aerosol type of the middle part was biomass burning or urban-industrial aerosol, while that of the other part was mixed aerosols. (2) The seasonal changes of AOD and AE indexes in each ecological functional area had obvious seasonal changes, and the AOD and AE values were highest in summer. At the same time, the proportion of biomass combustion or urban industrial aerosol was the highest in summer. (3) The ecological functional areas with fewer human activities were dominated by clean aerosols, with lower AOD and higher AE value. The ecological functional areas dominated by cities were dominated by mixed aerosols, with higher AOD. The ecological functional areas dominated by agriculture and heavy industry were dominated by biomass combustion or urban industrial aerosols, with the largest AOD. (4) Compared with 2015, the average AOD of each ecological functional area decreased significantly to 2020, and biomass combustion or urban industrial aerosols changed to mixed aerosols.

Five new diterpenes, including four new hydroazulenes, (8

Background Immediately placed implants with immediate provisionalization have become attractive options for patients and clinicians. However, there is no agreement on the esthetic advantages of immediately placed implants with immediate provisionalization. The aim of this systematic review and meta-analysis will be to assess the effect of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants in a single-tooth implant of the esthetic area. Methods An electronic search of MEDLINE/PubMed, EMBASE, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database will be performed. The search will be carried out in the databases for articles published until May 2021. Two researchers will independently perform the literature selection, data extraction and quality assessment. Only randomized controlled trials (RCTs) reporting on the impact of immediate provisionalization on the clinical esthetic outcomes of implants immediately placed in a single-tooth implant of the aesthetic area will be included. The primary outcome of this study will be the esthetic outcome assessed by the objective index and patient satisfaction. The survival rate of implants and restorations and the changes in mucosa and bone around implants will also be analyzed. The included studies will be analyzed by Review Manager 5.3, and a meta-analysis will be performed. Results The study will evaluate the clinical esthetic outcomes of immediately placed implants with and without immediate provisionalization in single-tooth implants of the esthetic area. The results will provide clinicians with a better treatment approach in their application. Conclusion This systematic review and meta-analysis will provide more reliable, evidence-based data for the impact of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants, which may or may not be beneficial. Registration number PROSPERO registration number: CRD42021221669.

Phytochemical investigation of the resin of Liquidambar formosana Hanc led to the separation and identification of five undescribed pentacyclic triterpenoids, including two lupane type, one taraxerane type, and two oleanane type triterpenoids, in addition to ten known analogues. Structures and relative or absolute configurations were elucidated by intensive spectroscopic methods, and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their anti-angiogenic effects in vitro against VEGF-induced endothelial cell proliferation and migration in HUVECs. Among them, (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one, (5R, 8R, 9R, 10R, 13S, 14R, 17S, 18S, 19S, 20S)-17, 20-peroxy-28- norlupa −29 -hydroxy- 3-one, 11α,12α:13β,28-diepoxyoleanane- 3-one, 28-norlup-20 (29)-ene- 3β,17β-diol, liquidambaric lactone and 13,28-epoxy-11- oleanene- 3-one significantly inhibited VEGF-induced HUVECs proliferation with IC50 values ranging from 1.64 ± 0.36 to 7.06 ± 0.28 μM. In addition, they also effectively decreased VEGF-induced cell migration with IC50 values ranging from 1.57 ± 0.60 to 4.77 ± 0.62 μM. The structure-activity relationship of these compounds is discussed. The anti-angiogenic property of (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one is mediated by the VEGFR2 - AKT signaling pathway.

This paper considers a parallel algorithm for Cholesky factorization on account of PBMD. Compared with the traditional data distribution for matrix-vector multiplication computation, the algorithm proposed incurs strictly less communication overhead and improves the load balancing. Experimental results demonstrate that the PBMD based matrix-vector multiplication computation makes the implementation of Cholesky factorization easier and enhances performance effectively.

Retinal inflammation in a hyperglycemic condition is believed to play a crucial role in the development of diabetic retinopathy, and targeting inflammatory mediators is a promising strategy for the control of diabetic retinopathy. Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. In this study, we demonstrate that treatment with curcumolide alleviated retinal inflammatory activities both in vitro and in vivo in a STZ-induced diabetic rat model and in TNF-α-stimulated HUVECs. Curcumolide alleviated retinal vascular permeability and leukostasis and attenuated the overexpression of TNF-α and ICAM-1 in diabetic retinas. Moreover, curcumolide also inhibited inducible p38 MAPK and NF-κB activation and the subsequent induction of proinflammatory mediators. These data suggest potential treatment strategies against diabetic retinopathy, particularly in the early stages of the disease.

Five new diterpenes, including an unprecedented 5,5,6,6,5-pentacyclic diterpene, sponalactone (1), two new spongian diterpenes, 17- O-acetylepispongiatriol (2) and 17- O-acetylspongiatriol (3), and two new spongian diterpene artifacts, 15α,16α-dimethoxy-15,16-dihydroepispongiatriol (4) and 15α-ethoxyepispongiatriol-16(15 H)-one (5), were isolated from a South China Sea collection of the marine sponge Spongia officinalis, together with three known analogues (6-8). The structures of the new diterpenes were elucidated by extensive spectroscopic analysis. The absolute configurations were established on the basis of ECD data. Compounds 1-5 and 7 exhibited moderate inhibition against LPS-induced NO production in RAW264.7 macrophages with IC

Four new steroids, named 7-dehydroerectasteroid F (1), 11α-acetoxyarmatinol A (2), 22,23-didehydroarmatinol A (3), and 3-O-acetylhyrtiosterol (4), together with 11 previously described analogues, were isolated from a South China Sea collection of the soft coral Dendronephthya gigantea. The structures of the new steroids were elucidated by comprehensive spectroscopic analysis and by comparison with previously reported data. Compound 1 showed potent protection against H2O2-induced oxidative damage in neuron-like PC12 cells by promoting nuclear translocation of Nrf2 and enhancing the expression of HO-1. 1 represents the first steroid-type antioxidant from marine organisms.

Background Targeting vascular endothelial growth factor is a common treatment strategy for neovascular eye disease, a leading cause of visual impairment and blindness. However, these approaches are limited or carry various complications. Therefore, there is an urgent need for the development of unique therapeutic approaches. Purpose To investigate the anti-angiogenic effects of curcumolide and its mechanism of action. Methods /Study designs In this study, we examine the effects of curcumolide on the process of vasculature formation, including cell proliferation, migration, tube formation and apoptosis in vitro using human umbilical vascular endothelial cells (HUVECs). We also assess the anti-angiogenic effects of curcumolide in vivo using a mouse model of oxygen induced retinopathy (OIR). The mechanism of anti-angiogenic effects was investigated by measuring the expression level of various signaling proteins and the molecular docking simulations. Results Intravitreal injection of curcumolide reduced the formation of retinal neovascular tufts and VEGFR2 phosphorylation in the murine OIR model at concentrations administered without definite cellular and retinal toxicities. Curcumolide suppressed VEGF-induced HRMECs proliferation, migration and tube formation in a dose-dependent manner. Meanwhile, it promoted caspase-dependent apoptosis. Curcumolide also inhibited VEGF-induced phosphorylation of VEGFR-2 tyrosine kinase, and suppressed downstream protein kinases of VEGFR2, including Src, FAK, ERK, AKT, and mTOR in HRMECs. In silico study revealed that curcumolide bound with ATP-binding sites of the VEGFR2 kinase unit by the formation of a hydrogen bond and hydrophobic interactions. Conclusion Curcumolide has anti-angiogenic activity in HUVECs and in a murine OIR model of ischemia-induced retinal neovascularization, and it might be a potential drug candidate for the treatment of proliferative diabetic retinopathy.

Background: The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations. Methods: The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed. Results: The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence. Conclusion: The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations. PROSPERO registration number: CRD42020167881.

A new species of Orbilia related to O. luteorubella is described mainly based on morphological characters of its asexual morph and molecular data. The sexual morph does not significantly differ from O. luteorubella, whereas the asexual morph obtained from its ascospore isolate resembles members of the non-predacious genus Dactylella, because it has fusiform phragmoconidia borne singly at the apex of conidiophores. Phylogenetic analysis showed that this strain clustered with a clade that included available strains of the O. luteorubella aggregate and was distant from all analysed Dactylella species. Within this clade, the new strain fell between species with filiform conidia and those of a Pseudotripoconidium anamorph. By combining morphological and phylogenetic analyses, we conclude that our isolate belongs to a new taxon. Pleomorphism of the new taxon is described and discussed.

Chemical investigation of the whole plants of Salvia substolonifera E.Peter yielded seven germacrane sesquiterpenoids, substolides A-G (1-7), an ethoxylated artifact (8), and two known analogues, 6β-tigloyloxyglechomafuran (9) and castanin F (10). Four germacrane 8-acetylation derivatives (1a-4a) were obtained by chemical transformation. Their structures and relative or absolute configurations were elucidated by intensive spectroscopic methods, and single-crystal X-ray diffraction analysis. Compounds 1a-4a, and 5-10 were evaluated for their in vitro anti-angiogenic effects. Compounds 7 and 9 significantly inhibited VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro, with IC50 values of 16.15 ± 0.19, and 4.03 ± 0.26 μM, respectively. The structure activity relationship of these compounds is discussed.

The mushroom genus Russula is among the largest and morphologically most diverse basidiomycete genera in the world. They are broadly distributed both geographically and ecologically, forming ectomycorrhizal relationships with a diversity of plants. Aside from their ecological roles, some Russula species are gourmet mushrooms. Therefore, understanding their population biology and fundamental life history processes are important for illustrating their ecological roles and for developing effective conservation and utilization strategies. Here, we review recent population genetic and molecular ecological studies of Russula. We focus on issues related to genet sizes, modes of reproduction, population structures, and roles of geography on their genetic relationships. The sampling strategies, molecule markers, and analytical approaches used in these studies will also be discussed. Our review suggests that in Russula, genets are typically small, local recombination is frequent, and that long-distance spore dispersal is relatively uncommon. We finish by discussing several long-standing issues as well as future trends with regard to life history and evolution of this important group of mushrooms.

Macrofungi refers to all fungi that produce visible fruiting bodies. These fungi are evolutionarily and ecologically very divergent. Evolutionarily, they belong to two main phyla, Ascomycota and Basidiomycota, and many of them have relatives that cannot form visible fruiting bodies. Ecologically, macrofungi can be associated with dead organic matter, plants, and animals. Here we review our current understanding of population structure and biogeography of macrofungi associated with animals. Their interactions, functions, and patterns of coevolution are described and discussed. Our focus is on studies using molecular markers. Our analyses suggest that the types of fungi–animal associations play an important role in the structure of these animal-associated fungal populations.

Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. The structure and absolute configuration were elucidated by extensive NMR, ECD data analysis, and a single-crystal X-ray study. This molecule exhibited significant anti-inflammatory effects in LPS-induced RAW 264.7 macrophages. It suppressed LPS-induced NF-κB activation, including the nuclear translocation and DNA binding activity of NF-κB, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitric oxide (NO) and reactive oxygen species (ROS) production. Therefore, Curcumolide may have therapeutic potential for treating inflammatory diseases by inhibiting NF-κB activation and pro-inflammatory mediator production.

Four new xenicanes, namely 4a-hydroxyisodictyohemiacetal (1), 4a-hydroxyisodictyoacetal (2), 13,18-diacetoxy-4-hydroxyisodictyo-19-al (3), and 4a-hydroxypachylactone (8), were isolated from a Chinese collection of the brown alga Dictyota plectens, along with four known analogues (4-7). The structures of the new diterpenes were determined by extensive spectroscopic data analysis. All compounds were evaluated for their antiviral activities against human immunodeficiency virus type 1 (HIV-1) and the highly pathogenic avian influenza A (H5N1) virus, and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages (PEM Phi).

Twenty-seven diterpenes of six chemical classes, including seven new diterpenes (1, 2, 6, 10, 11, 16, and 19), have been isolated from a collection of the brown alga Dictyota plectens from the South China Sea. The structures of the new diterpenes were elucidated by extensive spectroscopic analysis and by comparison with reported data. In the in vitro assays, 9, 12, 14, 16, and 22 showed inhibitory activity against HIV-1 replication with IC50 values of 16.1-30.5 μM, compounds 5, 13, 24, and 26 exhibited anti-H5N1 activity with inhibition rates of 50%-62% at 30.0 μM, and 12 and 24 also showed potent inhibition against LPS-induced NO production with inhibition rates of 90% and 86%, respectively, at 10.0 μM.

Chemical examination of a South China Sea soft coral Lobophytum sp. led to the isolation of three new α-methylene-γ-lactone-containing cembranoids, (1R*,3R*, 4R*,14R*,7E,11E)-3,4-epoxycembra-7,11,15(17)-trien-16,14-olide (1), (1R*,7S*,14S*,3E, 11E)-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (2), and (1R*,7S*,14S*, 3E,11E)-18-acetoxy-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (3), along with eleven known analogues 4-14. The structures of the new compounds were elucidated through extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1-3 exhibited moderate cytotoxic activity against the selected tumor cell lines. Moreover, 2 and 3 were found to be moderate inhibitors against the bacteria S. aureus and S. pneumoniae.

Six new casbane diterpenoids, named as sinularcasbanes A–F (1–6), along with six known analogues 7–12, were isolated from a South China Sea soft coral, Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with data reported in the literature. All compounds were evaluated for their cytotoxicity against selected cancer cell lines and the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.

Four new 7,8-epoxycembranoids, namely (2S*,7S*,8S*,12R*,1Z,3E,10E)-7,8:2,16-diepoxycembra-1(15), 3,10-trien-12-ol (1), (2S*,7S*,8S*,11R*,1Z,3E)-7,8:2,16-diepoxycembra-1(15),3,12(20)-trien-11-ol (2), (4S*, 7S*,8S*,1Z,2E,11E)-16-acetoxy-7,8-epoxycembra-1(15),2,11-trien-4-ol (3), and (7S*,8S*,15S*,1E,3E,11E)-7,8-epoxycembra-1,3,11-trien-15,16-diol (4) were isolated from a Chinese soft coral Lobophytum sp., together with eleven known analogues 5-15. The structures of the new compounds were determined by extensive spectroscopic data analysis. All compounds were tested for the inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages (PEM Phi).

Two new sesquiterpenoids, namely elema-1,3,7(11),8-tetraen-8,12-lactam (1) and 7β,8α-dihydroxy-1α,4αH-guai-9,11-dien-5β,8β-endoxide (2), together with five known analogs were isolated from the EtOAc extract of the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D-NMR techniques. All compounds were tested for the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compound 1 showed the significant inhibitory activity with IC50 values of 9.4 µM.

Ten new cembrane-based diterpenes, locrassumins A–G (1–7), (–)-laevigatol B (8), (–)-isosarcophine (9), and (–)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum, together with eight known analogues (11–18). The structures of the new compounds were determined by extensive spectroscopic analysis and by comparison with previously reported data. Locrassumin C (3) possesses an unprecedented tetradecahydrobenzo[3,4]cyclobuta[1,2][8]annulene ring system. Compounds 1, 7, 12, 13, and 17 exhibited moderate inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC50 values of 8–24 μM.

Nineteen metabolites with diverse structures, including the rare pyrroloindoline alkaloid verrupyrroloindoline (1), the unprecedented highly fused benzosesquiterpenoid verrubenzospirolactone (2), the new asteriscane-type sesquiterpenoid 10-deoxocapillosanane D (3), and the two new cyclopentenone derivatives (4S*,5S*)-4-hydroxy-5-(hydroxymethyl)-2,3-dimethyl-4-pentylcyclopent-2-en-1-one (4) and (S)-4-hydroxy-5-methylene-2,3-dimethyl-4-pentylcyclopent-2-en-1-one (5), were isolated from a South China Sea collection of the soft coral Sinularia verruca. Eleven previously described marine metabolites (7–15, 18, and 19) were also obtained as well as three new EtOH-adduct artifacts (6, 16, and 17). The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 4, 5, and 16 showed protection against the cytopathic effects of HIV-1 infection with EC50 values of 5.8–34 μM, and 4, 6, and 16 exhibited inhibition against LPS-induced NO production with IC50 values of 24–28 μM.

A sensitive and selective liquid chromatography mass spectrometry method for determination of curdione in rabbit plasma was developed. After addition of tramadol as internal standard (IS), protein precipitation by acetonitrile was used for sample preparation. Chromatographic separation was achieved on a Zorbax SB-C₁₈ (2.1 × 50 mm, 3.5 µm) column with acetonitrile-0.1% formic acid as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive-ion mode; selective ion monitoring was used for quantification using target fragment ions m/z 237 for curdione and m/z 264 for the IS. Calibration plots were linear over the range of 20-4000 ng/mL for curdione in plasma. The lower limit of quantification for curdione was 20 ng/mL. Mean recovery of curdione from plasma was in the range 94.3-98.4%. The RSD of intra-day and inter-day precision were both less than 9%. This method is simple and sensitive enough to be used in pharmacokinetic research for the determination of curdione in rabbit plasma.

isolation, structural elucidation and inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages

Two new sesquiterpenoids, namely elema-1,3,7(11),8-tetraen-8,12-lactam (1) and 7β,8α-dihydroxy-1α,4αH-guai-9,11-dien-5β,8β-endoxide (2), together with five known analogs were isolated from the EtOAc extract of the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D-NMR techniques. All compounds were tested for the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compound 1 showed the significant inhibitory activity with IC50 values of 9.4 µM.

Two new sesquiterpenoids, namely elema-1,3,7(11),8-tetraen-8,12-lactam (1) and 7β,8α-dihydroxy-1α,4αH-guai-9,11-dien-5β,8β-endoxide (2), together with five known analogs were isolated from the EtOAc extract of the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D-NMR techniques. All compounds were tested for the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compound 1 showed the significant inhibitory activity with IC50 values of 9.4 µM.

Objective To conduct a preliminary study on the effect of curcumol in promoting angiogenesis activity and its mechanism in zebrafishes, in order to provide basis for clinical prescription. Method Zebrafishes biological model was established to, observe curcumol's effect on embryo blood vessel growth, blood vessel regeneration of adult fishes after tail-cutting and tissue regeneration of fish fries after tail-cutting. The relative fluorescence quantitative PCR method was adopted to determine the gene expression of vascular endothelial growth factor (VEGFA) and receptor VEGFR2 of fish fries after tail-cutting. Result Curcumol contributed to angiogenesis of intersegmental blood vessels in zebrafishes embryos and speed up regeneration of blood vessels in adult fishes after tail-cutting. Furthermore, curcumol can increase the gene expression of VEGFA and VEGFR2 in fish fries. Conclusion Curcumol can promote angiogenesis in zebrafishes, and enhance the gene expression of VEGFA and VEGFR2 in fish fries after tail-cutting and speed up the regeneration of their tails.

To study the chemical constituents of Hemsleya chensnsis.Various chromatographic techniques were used to separate and purify the constituents. The spectral data (MS, NMR) were obtained for structure elucidation.Eight known triterpenoid saponins were isolated from the root of H. chensnsis. Their structures were elucidated as dihydrocucurbitacin B (1), 25-O-acetyl-dihydrocucurbitacin F (2), cucurbitacin F (3), 3-O-(6'-ethyl ester) -beta-D-glucuropyranosyl oleanolic acid-28-O-alpha-L-arabinopyranoside (4), oleanolic acid-3-(6'-methyl ester) -beta-D-glucuropyranosyl (1-3) -alpha-L-arabinopyranoside (5), oleanolic acid-28-O-beta-D-glucopyranosyl-(1-6) -beta-D-glucopyranoside (6), 3-O-(6'-methyl ester) -beta-D-glucuropyranosyl oleanolic acid-28-O-beta-D-glucopyranosyl-(1-6) -beta-D-glucopyranoside (7), 3-O-(6'-methyl ester) -beta-D-glucuropyranosyl (1-2) -beta-D-glucopyranoside-oleanolic acid-28-O-beta-D-glucopyranoside (8).All compounds except for 2 were isolated from H. chensnsis for the first time.

BACKGROUND: Angiogenesis plays an important role in many physiological and pathological processes. Identification of small molecules that block angiogenesis and are safe and affordable has been a challenge in drug development. Hypericum attenuatum Choisy is a Chinese herb medicine commonly used for treating hemorrhagic diseases. The present study investigates the anti-angiogenic effects of quercetin-4'-O-β-D-glucopyranoside (QODG), a flavonoid isolated from Hypericum attenuatum Choisy, in vivo and in vitro, and clarifies the underlying mechanism of the activity. METHODOLOGY/PRINCIPAL FINDINGS: Tg(fli1:EGFP) transgenic zebrafish embryos were treated with different concentrations of quercetin-4'-O-β-D-glucopyranoside (QODG) (20, 60, 180 µM) from 6 hours post fertilisation (hpf) to 72 hpf, and adult zebrafish were allowed to recover in different concentrations of QODG (20, 60, 180 µM) for 7 days post amputation (dpa) prior morphological observation and angiogenesis phenotypes assessment. Human umbilical vein endothelial cells (HUVECs) were treated with or without VEGF and different concentrations of QODG (5, 20, 60, 180 µM), then tested for cell viability, cell migration, tube formation and apoptosis. The role of VEGFR2-mediated signaling pathway in QODG-inhibited angiogenesis was evaluated using quantitative real-time PCR (qRT-PCR) and Western blotting. CONCLUSION/SIGNIFICANCE: Quercetin-4'-O-β-D-glucopyranoside (QODG) was shown to inhibit angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo via suppressing VEGF-induced phosphorylation of VEGFR2. Our results further indicate that QODG inhibits angiogenesis via inhibition of VEGFR2-mediated signaling with the involvement of some key kinases such as c-Src, FAK, ERK, AKT, mTOR and S6K and induction of apoptosis. Together, this study reveals, for the first time, that QODG acts as a potent VEGFR2 kinase inhibitor, and exerts the anti-angiogenic activity at least in part through VEGFR2-mediated signaling pathway.

Five sesquiterpenoids, 1α,8α-epidioxy-4α-hydroxy- 5αH-guai-7(11),9-dien- 12,8-olide. (1), 8,9-seco-4β-hydroxy-1α,5βH-7(11)-guaen-8,10-olide (2), 8α-hydroxy-1α, 4β,7βH-guai-10(15)-en- 5β,8β-endoxide(3), 7β,8α-dihydroxy-1α,4αH-guai-10(15)-en-5β,8β-endoxide(4) and 7-hydroxy-5(10),6,8-cadinatriene-4-one(5), together with seven known analogs were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D NMR techniques, and the structures of 1 and 2 were confirmed by single-crystal X-ray diffraction experiment. Compounds 1-10 and 12 showed significant in vitro antiviral activity against the influenza virus A with IC₅₀ values ranged from 6.80 to 39.97 μM, and SI values ranged from 6.35 to 37.25.

A sensitive and selective liquid chromatography mass spectrometry method for determination of curdione in rabbit plasma was developed. After addition of tramadol as internal standard (IS), protein precipitation by acetonitrile was used for sample preparation. Chromatographic separation was achieved on a Zorbax SB-C₁₈ (2.1 × 50 mm, 3.5 µm) column with acetonitrile-0.1% formic acid as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive-ion mode; selective ion monitoring was used for quantification using target fragment ions m/z 237 for curdione and m/z 264 for the IS. Calibration plots were linear over the range of 20-4000 ng/mL for curdione in plasma. The lower limit of quantification for curdione was 20 ng/mL. Mean recovery of curdione from plasma was in the range 94.3-98.4%. The RSD of intra-day and inter-day precision were both less than 9%. This method is simple and sensitive enough to be used in pharmacokinetic research for the determination of curdione in rabbit plasma.

To study the triterpenoid saponins in Hemsleya chensnsis.The chemical constituents were isolated and purified by various chromatographic methods and their structures were elucidated on the basis of spectral analysis.Seven known triterpenoid saponins were isolated from the root of H. chensnsis and were identified as 3-O-beta-D-glucuropyranosyl-oleanol-icacid (1), 3-O-beta-D-glucopyra-noside-oleanolicacid-28-O-beta-D-glucopyranoside (2), 3-O-(6'-methylester)-beta-D-glucuropyranosyl olea- nolic acid-28-O-alpha-L-arabinopyranoside (3), 3-O-(6'-methylester)-beta-D- glucuropyranosyl- oleanolic acid-28-O-beta-D-mannupyranoside (4), 3-O-(6'-ethyl ester)-beta-D-glucuropyranosyl oleanolic acid-28-O-beta-D- glucopyranoside (5), 3-O-alpha-L-arabinopyranoside-(1--3) -beta-D-glucuropyranosyl- oleanolic acid-28-O-beta-D-glucopyranoside (6), 3-O-beta-D-glucu-ropyranosyl-oleanolic acid-28-O-beta-D-glucopyra-noside-(1--6)-beta-D-glucopyranoside (7).Compounds 1-7 were isolated from this plant for the first time.