Antibacterial Indole-diterpenoid Alkaloids from the Marine Fungus Penicillium sp. ZYX-Z-718.

Two new indole-diterpenoids, penpaxilloids F and G (1 and 2), along with 11 known analogues (3-13), were isolated from the marine fungus Penicillium sp. ZYX-Z-718. The structures of the new compounds were identified by extensive spectroscopic analyses including HR-ESI-MS, UV, and NMR, as well as theoretical NMR chemical shifts and ECD calculations. Compounds 6 and 10 showed antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and MRSA with MIC values ranging from 16.0 to 32.0 µg/mL.

Persteroid, a new steroid from the marine-derived fungus Penicillium sp. ZYX-Z-143.

A new steroid named persteroid (1) and seven known compounds (2-8) were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. The structure of 1 was determined by HRESIMS, NMR, and ECD calculations. Compound 1 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 46.31 ± 0.52 µM. Moreover, compound 1 potently suppressed nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The cytotoxicity and antibacterial activity of all isolates were tested.

Reprogramming of DNA methylation and changes of gene expression in grafted Hevea brasiliensis.

Rubber tree (Hevea brasiliensis) is reproduced by bud grafting for commercial planting, but significant intraclonal variations exist in bud-grafted clones. DNA methylation changes related to grafting may be partly responsible for intraclonal variations. In the current study, whole-genome DNA methylation profiles of grafted rubber tree plants (GPs) and their donor plants (DPs) were evaluated by whole-genome bisulfite sequencing. Data showed that DNA methylation was downregulated and DNA methylations in CG, CHG, and CHH sequences were reprogrammed in GPs, suggesting that grafting induced the reprogramming of DNA methylation. A total of 5,939 differentially methylated genes (DMGs) were identified by comparing fractional methylation levels between GPs and DPs. Transcriptional analysis revealed that there were 9,798 differentially expressed genes (DEGs) in the DP and GP comparison. A total of 1,698 overlapping genes between DEGs and DMGs were identified. These overlapping genes were markedly enriched in the metabolic pathway and biosynthesis of secondary metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Global DNA methylation and transcriptional analyses revealed that reprogramming of DNA methylation is correlated with gene expression in grafted rubber trees. The study provides a whole-genome methylome of rubber trees and an insight into the molecular mechanisms underlying the intraclonal variations existing in the commercial planting of grafted rubber trees.

Phytohabitans maris sp. nov., isolated from marine sediment.

A novel actinobacterium, strain ZYX-F-186T, was isolated from marine sediment sampled on Yongxing Island, Hainan Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain ZYX-F-186T belongs to the genus Phytohabitans, with high similarity to Phytohabitans kaempferiae KK1-3T (98.3 %), Phytohabitans rumicis K11-0047T (98.1 %), Phytohabitans flavus K09-0627T (98.1 %), Phytohabitans houttuyneae K11-0057T (97.9 %), Phytohabitans suffuscus K07-0523T (97.7 %), and Phytohabitans aurantiacus RD004123T (97.7 %). Phylogenetic analysis of 16S rRNA gene sequences showed that the strain formed a single subclade in the genus Phytohabitans. The novel isolate contained meso-diaminopimelic acid, d-glutamic acid, glycine, d-alanine, and l-lysine in the cell wall. The whole-cell sugars were xylose, arabinose, ribose, and rhamnose. The predominant menaquinones were MK-9(H8), MK-9(H6), and MK-9(H4). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylglycerol, and an unknown phospholipid. The major fatty acids (>5 %) were iso-C16 : 0, anteiso-C17 : 0, and iso-C18 : 0. Genome sequencing showed a DNA G+C content of 71.9 mol%. Low average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values demonstrated that strain ZYX-F-186T could be readily distinguished from its closely related species. Based on its phylogenetic, chemotaxonomic, and physiological characteristics, strain ZYX-F-186T represents a novel species of the genus Phytohabitans, for which the name Phytohabitans maris sp. nov. is proposed. The type strain is ZYX-F-186T (=CGMCC 4.8025T=CCTCC AA 2023025T=JCM 36507T).

Bi-2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria filaria in the Philippines.

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.

Diaporchalasins A-E, New Cytochalasins from the Endophytic Fungus Diaporthe sp. BMX12 Isolated from Aquilaria sinensis.

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 µM.

The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.

OBJECTIVE: To investigate the roles and underlying mechanisms of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer (GC). METHODS: VEGFR-3 gene expression profiles in human gastric adenocarcinoma (GAC) tissues were analysed using The Cancer Genome Atlas database. Human GC cell lines and were used for in vitro studies. Mouse models of GC and distant metastasis were used for in vivo studies. Silencing of VEGFR-3 gene expression was achieved using small interfering RNA. RESULTS: VEGFR-3 gene expression was significantly elevated in GAC tissues and GC cells. Higher VEGFR-3 expression was positively correlated with more advanced stages and a greater number of metastatic lymph nodes. In vitro studies in GC cells showed that knockdown of VEGFR-3 gene expression significantly suppressed cell proliferation and migration, but promoted apoptosis. In vivo investigations revealed that silencing of VEGFR-3 gene expression exhibited significant inhibition on tumour growth and metastasis. Further mechanistic studies showed that VEGFR-3 exerted its pathological roles by affecting the key molecules in the apoptotic and epithelial-mesenchymal transition pathways. CONCLUSION: The molecular pathways associated with VEGFR-3-mediated pathological effects could be targets in the development of novel approaches for the diagnosis, prognosis and treatment of GC.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria.

Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143.

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 µM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 µM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Diverse ansamycin derivatives from the marine-derived Streptomyces sp. ZYX-F-97 and their antibacterial activities.

Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5-12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4, 8, and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 µg·mL-1 to 64 µg·mL-1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 µg·mL-1. Compounds 4, 8, 9, and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 µg·mL-1 to 128 µg·mL-1.

Chemical constituents of the marine-derived fungus Acremonium sp. AN-13.

Two new compounds named 3(S)-hydroxy-1-(2,4,5-trihydroxy-3,6- dimethylphenyl)-hex-4E-en-1-one (1) and acremonilactone (2), together with nine known compounds (3-11), were isolated from the fermentation broth of Acremonium sp. associated with marine sediments collected from South China Sea. NMR and HRESIMS spectroscopic analysis elucidated the structure of two new compounds. Compound 2 had characteristic rotary gate shape skeleton with a six-membered lactone. Compounds 1 and 9 showed DPPH radical scavenging activity with inhibition rates of 96.50 and 85.95% at the concentration of 0.5 mg/ml, respectively. Moreover, compounds 4, 6 and 11 showed definite antibacterial activity against Staphylococcus aureus ATCC 6538.

Sesquiterpenoids and bibenzyl derivative from Dendrobium hercoglossum.

Three new sesquiterpenoids, dendrohercoglin A - C (1-3), and one new bibenzyl derivative, dendronbiline D (4), together with nine known sesquiterpenoids (5-13) were isolated from Dendrobium hercoglossum. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. All the compounds were evaluated for their neuroprotective and anti-inflammatory activities. Compounds 2 and 3 increased the H2O2-damaged SH-SY5Y cell viabilities from 43.3% to 58.6% and 68.4%, respectively. Compound 4 exhibited pronounced anti-inflammatory activity with IC50 value of 9.5 ± 0.45 µM which was superior to the reference compound quercetin (IC50: 15.7 ± 0.89 µM).

Identification of volatile compounds and their bioactivities from unpolar fraction of Alpinia oxyphylla Miq. and mining key genes of nootkatone biosynthesis.

In this study, analysis of the chemical constituents and bioactivities of the unpolar fractions [petroleum ether (PE) and chloroform (C)] of fruits and leaves of Alpinia oxyphylla Miq. were carried out, as well as the bioactivities of the main compounds nootkatone and valencene. From PE and C fractions of the fruits, and PE fraction of the leaves, 95.80%, 59.30%, and 82.11% of the chemical constituents respectively were identified by GC-MS. Among these identified compounds, nootkatone was the main compound in all of three fractions, while valencene was the second main compound in the PE fractions of the fruits and leaves. The bioactivities results showed that all of the fractions and the major compound nootkatone showed tyrosinase inhibitory, as well as inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. While valencene only presented inhibitory activity on NO production in RAW264.7 cells. The critical genes involved in nootkatone biosynthesis in A. oxyphylla were identified from the public transcriptome datasets, and protein sequences were preliminarily analyzed. Our studies develop the usage of the unpolar fractions of A. oxyphylla, especially its leaves as the waste during its production, and meanwhile provide the gene resources for nootkatone biosynthesis.

Two new anti-inflammatory trachylobane diterpenoids from Euphorbia atoto.

Two new rare trachylobane euphoratones A-B (1-2), together with five known diterpenoids (compounds 3-7), were isolated from the aerial parts of Euphorbia atoto. Their structures were unambiguously elucidated through HRESIMS, 1D and 2D NMR spectral analysis. Compounds 1, 3, 4 and 7 showed weak anti-inflammatory activities (IC50 77.49 ± 6.34, 41.61 ± 14.49, 16.00 ± 1.71 and 33.41 ± 4.52 µM, respectively), compared to the positive control quercetin (IC50 15.23 ± 0.65 µM).

Lanostane triterpenoids from the fruiting bodies of Ganoderma amboinense.

Lanostane-type triterpenoids are the main characteristic constituents in Ganoderma mushrooms. Phytochemical analysis on the ethanol extract of the fruiting bodies of Ganoderma amboinense led to isolation and identification of twelve previously undescribed lanostane triterpenoids (1-12). Their chemical structures were determined by HR-ESI-MS, IR, and NMR spectroscopic analysis, NMR calculation, as well as X-ray crystallography. All isolates were evaluated for the α-glucosidase inhibitory and anti-inflammatory activities. Compounds 1, 5, 6, and 11 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 33.5 µM to 96.0 µM. Moreover, compound 12 showed anti-inflammatory activity with IC50 value of 21.7 ± 2.1 µM.

Surgical treatment of mixed cervical spondylosis with spontaneous cerebrospinal fluid leakage: A case report.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks associated with cervical spondylosis are rare. To our knowledge, only a few cases have been reported in which treatment is challenging and varies from case to case. Here, we review the literature and describe the surgical treatment of a 70-year-old woman who presented with a CSF leak due to a cervical spine spur. CASE SUMMARY: A 70-year-old female patient who was treated for a cerebral infarction, presented with complains of weakness in the right lower extremity and a feeling of stepping on cotton. The patient underwent regular neck massage and presented with neck and right shoulder pain radiating to the right upper extremity one-month ago. Magnetic resonance imaging showed a strip of leaking cerebrospinal fluid posterior to the C1-4 vertebrae, and computed tomography showed a "sickle-shaped" disc prolapse with calcification in C4/5. We chose to perform an anterior cervical discectomy. When the prolapsed C4/5 disc was scraped, clear fluid leakage was observed, and exploration revealed a 1 mm diameter rupture in the anterior aspect of the dura mater, which was compressed continuously with cotton patties, with no significant cerebrospinal fluid leakage after 1 h. CONCLUSION: Three months after surgery, the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

Evaluating the Antioxidant Properties of the Leaves and Stems of Alpinia oxyphylla In Vitro and Its Growth-Promoting, Muscle Composition Change, and Antioxidative Stress Function on Juvenile Litopenaeus vannamei.

Alpinia oxyphylla is a homology of medicine and food. This study aims to investigate the dominant chemical composition and explore the antioxidant properties of the ethanol extract of the leaves and stems of A. oxyphylla (AOE) on juvenile shrimp, Litopenaeus vannamei. An in vitro test showed that AOE and its dominant chemical composition procyanidin B-2 (1) and epicatechin (2) presented DPPH and ABTS radical scavenging activities. A shrimp feeding supplement experiment revealed that shrimp growth parameters and muscle composition were improved significantly when fed with a 200 mg/Kg AOE additive. Meanwhile, the activities of antioxidant enzymes (CAT, GSH-Px, SOD, and T-AOC) in serum and the liver and the expression of related genes (LvMn-SOD, LvCAT, LvproPo, and LvGSH-Px) were enhanced with various degrees in different AOE additive groups while the content of MDA was significantly decreased. Moreover, the antioxidative effect of AOE additive groups on shrimp was also observed in an acute ammonia nitrogen stress test.

Diverse indole-diterpenoids with protein tyrosine phosphatase 1B inhibitory activities from the marine coral-derived fungus Aspergillus sp. ZF-104.

Eight previously undescribed indole-diterpenoids named penerpenes O-V (1-8), together with seven known analogues (9-14), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Their structures including the absolute configurations of these compounds were assigned on the basis of spectroscopic data and ECD analysis along with quantum ECD and NMR calculations. Compounds 4 and 5 bear rare indolin-2-one units in their structures and 6 bears a reconstructed novel skeleton in which the indole ring and the terpenoid substructure are cleaved before they are reconnected through the nitrogen atom. Compounds 1, 2, 7, and 10 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activities comparable to that of the positive control NaVO3.

Lanostane triterpenoids with anti-proliferative and PTP1B/α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma calidophilum.

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 µM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC50 values of 30.2 ± 0.13 µM and 120.6 ± 0.14 µM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations.

A theoretical calculation method of seismic shear key pounding based on continuum model.

The evolution of shear key design for bridges is accompanied by research on structural earthquake resistance. However, the vast majority of pounding forces, responses, and corresponding data for the study and design of shear keys have been based on expensive experimentalism and imprecise empiricism approaches for decades. Hence, strengthening theoretical study on seismic performance of shear key is essential. In this paper, a "Beam-Spring-Beam + Concentrated Mass" continuum dynamic model is proposed. Meanwhile, the transient wave function expansion method and the mode superposition method are applied to determine the analytical expression of the dynamic response from the girder and pier system (pier and cap beam). Furthermore, the combined transient internal force method and Duhamel integration method are introduced to assess the elastic pounding process. Through programming and numerical analysis, a series of pounding response data related to the shear key under various working circumstances will be explored. As mentioned above, the proposed theoretical method can optimize shear key design and boost the reliability of seismic limiting devices in the future. •Establishing a feasible "Beam-Spring-Beam + Concentrated Mass" continuum model of girders and piers based on a two-span continuous girder bridge.•Deriving the analytical solutions of responses by conducting the response equations under horizontal seismic excitation (containing orthonormality verification).•Simulating the pounding process by embedding elastic pounding calculation methods into Continuum Model.