Metabolomics analysis of physicochemical properties associated with freshness degradation in frozen Antarctic krill (Euphausia superba).

This study aimed to determine the effect of different frozen temperatures during storage on the quality of Antarctic krill (Euphausia superba) and assess the change at the metabolite level via a combination of physicochemical property analysis, liquid chromatography-tandem mass spectrometry (LC-MS) based non-targeted metabolomics profiling. Regarding samples stored at -20 °C, the expressions of 7055 metabolites were elevated, while 2313 were downregulated. Lipids and lipid molecules had the highest proportion of differential metabolites. A total of 432 discriminatory metabolites with Kyoto Encyclopedia of Genes and Genomes (KEGG) IDs was obtained. We also observed that the concentrations of differential bitter free amino acids (FAAs) and oxidation products of arachidonic and linoleic acid increased. Moreover, as the storage temperature increased, the freshness, umami, and sweetness components were considerably reduced. Furthermore, results indicated that the color, pH and water-holding capacity (WHC) were potential indicators of quality deterioration, while inosinic acid was a probable biomarker for umami degradation of frozen Antarctic krill. In conclusion, this study demonstrates that storage at lower temperatures can be beneficial for maintaining the freshness of Antarctic krill from macro and micro perspectives.

Discovering a New Okadaic Acid Derivative, a Potent HIV Latency Reversing Agent from Prorocentrum lima PL11: Isolation, Structural Modification, and Mechanistic Study.

Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common shellfish toxins, okadaic acid (OA) (1) and OA methyl ester (2), were isolated from the cultured microalgae strain Prorocentrum lima PL11. OA can significantly activate the latent HIV but has severe toxicity. To obtain more tolerable and potent latency reversing agents (LRAs), we conducted the structural modification of OA by esterification, yielding one known compound (3) and four new derivatives (4-7). Flow cytometry-based HIV latency reversal activity screening showed that compound 7 possessed a stronger activity (EC50 = 46 ± 13.5 nM) but was less cytotoxic than OA. The preliminary structure-activity relationships (SARs) indicated that the carboxyl group in OA was essential for activity, while the esterification of carboxyl or free hydroxyls were beneficial for reducing cytotoxicity. A mechanistic study revealed that compound 7 promotes the dissociation of P-TEFb from the 7SK snRNP complex to reactivate latent HIV-1. Our study provides significant clues for OA-based HIV LRA discovery.

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5−10) and three homodimers (2−4), together with their monomers including three aromatic bisabolanes (11−13) and two diphenyl ethers (14 and 15). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis including HRESIMS, 1D/2D NMR, calculated ECD, and the optical rotatory data. Among the four new compounds, (+/−)-asperbisabol A (1a/1b), asperbisabol B (2), and asperbisabol C (3), the enantiomers 1a and 1b represent an unprecedented skeleton of diphenyl ether-coupled aromatic bisabolane sesquiterpenoids with a spiroketal core moiety. The neuroprotective effects of selected compounds against sodium nitroprusside (SNP)-induced injury were evaluated in PC12 cells by the MTT assay. Five compounds (1a, 6, and 8−10) showed remarkable neuroprotective activities at 10 µM, being more active than the positive control edaravone.

Combined Effects of Temperature and Toxic Algal Abundance on Paralytic Shellfish Toxic Accumulation, Tissue Distribution and Elimination Dynamics in Mussels Mytilus coruscus.

This study assessed the impact of increasing seawater surface temperature (SST) and toxic algal abundance (TAA) on the accumulation, tissue distribution and elimination dynamics of paralytic shellfish toxins (PSTs) in mussels. Mytilus coruscus were fed with the PSTs-producing dinoflagellate A. catenella under four simulated environment conditions. The maximum PSTs concentration was determined to be 3548 µg STX eq.kg-1, which was four times higher than the EU regulatory limit. The increasing SST caused a significant decline in PSTs levels in mussels with rapid elimination rates, whereas high TAA increased the PSTs concentration. As a result, the PSTs toxicity levels decreased under the combined condition. Additionally, toxin burdens were assessed within shellfish tissues, with the highest levels quantified in the hepatopancreas. It is noteworthy that the toxin burden shifted towards the mantle from gill, muscle and gonad at the 17th day. Moreover, variability of PSTs was measured, and was associated with changes in each environmental factor. Hence, this study primarily illustrates the combined effects of SST and TAA on PSTs toxicity, showing that increasing environmental temperature is of benefit to lower PSTs toxicity with rapid elimination rates.

Draft Genome Sequences of Nine Cultivable Heterotrophic Proteobacteria Isolated from Phycosphere Microbiota of Toxic Alexandrium catenella LZT09.

Microscopic interactions between phycosphere microbiota and host algae play crucial roles in aquatic ecosystems. Despite their significance, there is a scarcity of available genome sequences derived from the phycosphere microbiome. Here, we report the draft genome sequences of nine heterotrophic proteobacterial strains isolated from the toxic dinoflagellate Alexandrium catenella LZT09 during execution of our Phycosphere Microbiome Project. Further exploration of the genomic features of the alga-associated bacterial community will profoundly help in deeply deciphering the processes and mechanisms governing the host-microbe interactome within algal holobionts in the ocean.

Biosynthetic Potential of a Novel Antarctic Actinobacterium Marisediminicola antarctica ZS314T Revealed by Genomic Data Mining and Pigment Characterization.

Rare actinobacterial species are considered as potential resources of new natural products. Marisediminicola antarctica ZS314T is the only type strain of the novel actinobacterial genus Marisediminicola isolated from intertidal sediments in East Antarctica. The strain ZS314T was able to produce reddish orange pigments at low temperatures, showing characteristics of carotenoids. To understand the biosynthetic potential of this strain, the genome was completely sequenced for data mining. The complete genome had 3,352,609 base pairs (bp), much smaller than most genomes of actinomycetes. Five biosynthetic gene clusters (BGCs) were predicted in the genome, including a gene cluster responsible for the biosynthesis of C50 carotenoid, and four additional BGCs of unknown oligosaccharide, salinixanthin, alkylresorcinol derivatives, and NRPS (non-ribosomal peptide synthetase) or amino acid-derived compounds. Further experimental characterization indicated that the strain may produce C.p.450-like carotenoids, supporting the genomic data analysis. A new xanthorhodopsin gene was discovered along with the analysis of the salinixanthin biosynthetic gene cluster. Since little is known about this genus, this work improves our understanding of its biosynthetic potential and provides opportunities for further investigation of natural products and strategies for adaptation to the extreme Antarctic environment.

Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer.

INTRODUCTION: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. MATERIALS AND METHODS: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd-Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. RESULTS: Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s-1 mM-1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s-1 mM-1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. CONCLUSION: Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC.

Unusual Cytotoxic Steroidal Saponins from the Gorgonian Astrogorgia dumbea.

Three steroidal saponins, including astrogorgiosides A (1) and B (2) bearing acetamido-glucose moieties, and astrogorgioside C (3) with a 19-nor and bearing an aromatized B ring steroid aglycone, together with a known major saponin dimorphoside A (4), were obtained from the gorgonian Astrogorgia dumbea collected near Dongshan Island in East China Sea. Structures of these compounds were elucidated by in-depth spectral and chemical methods, including 2D-NMR, HR-ESI-MS spectra, and acidic hydrolysis. For the first time, acetamido-glucose moiety is being reported from a gorgonian. The B-ring aromatized steroid aglycone of compound 3 is also rare in marine natural products. Compounds 1-3 exhibited moderate cytotoxic activity with IC50 values of 26.8-45.6 µM against human tumor cells Bel-7402 and K562.

Bioactive cembranoids from the South China Sea soft coral Sarcophyton elegans.

Four new cembranoids, sarcophelegans A-D (1-4) and six known analogues (5-10) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were elucidated through detailed spectroscopic analysis, and the absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The antimigratory potential of compounds 1-10 were evaluated and compounds 2 and 6 were found to inhibit human breast tumor MDA-MB-231 cell migration at 10 µM.

Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.

Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 µM, and compound 15 (IC50 = 1.4 µM) showed comparable activity to the positive control rolipram (IC50 = 0.60 µM). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.

Six new tetraprenylated alkaloids from the South China Sea gorgonian Echinogorgia pseudossapo.

Six new tetraprenylated alkaloids, designated as malonganenones L-Q (1-6), were isolated from the gorgonian Echinogorgia pseudossapo, collected in Daya Bay of Guangdong Province, China. The structures of 1-6 featuring a methyl group at N-3 and a tetraprenyl chain at N-7 in the hypoxanthine core were established by extensive spectroscopic analyses. Compounds 1-6 were tested for their inhibitory activity against the phosphodiesterases (PDEs)-4D, 5A, and 9A, and compounds 1 and 6 exhibited moderate inhibitory activity against PDE4D with IC50 values of 8.5 and 20.3 µM, respectively.

Bioactive polyhydroxylated sterols from the marine sponge Haliclona crassiloba.

Four new polyhydroxylated sterols, named halicrasterols A-D (1-4), together with six known analogs (5-10) were isolated from the marine sponge Haliclona crassiloba. Compounds 1 and 2 represented rare examples of steroids featuring 17(20)E-double bonds. The structures of 1-10 were elucidated by spectroscopic analysis and comparison with reported data. This is the first report of a steroid profile for this species. The antimicrobial activities of 1-10 were evaluated against a panel of bacterial and fungal strains in vitro, and compounds 4 and 9 showed moderate activity against some of the Gram-positive strains with MICs ranging from 4 to 32 µg/mL.

[Purine and carboline alkaloids from ascidian Symplegma oceania].

Five purine and carboline alkaloids were isolated from the methanol extract of the ascidian Symplegma oceania. Classic chromatographies including preparative HPLC were used for isolation and purification of the compounds. The structures were established as 6-methoxy-7-methyl-8-oxoguanine (1), 2-methylimino-3-methyl-6-methylamino- 9H-purine (2), 1,2,3,4-tetrahydro-betacarboline (3), 1,2,3,4-tetrahydro-1-methyl-beta-carboline (4) and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (5) by comparison the spectroscopic data (MS, 1H, 13C-NMR) with those reported in the literatures. Compounds 2-5 were reported from the the genus Symplegma for the first time. The purine and carboline were the major alkaloid types of S. oceania.

Angustimine and angustifolimine: two new alkaloids from Daphniphyllum angustifolium.

Two new alkaloids, angustimine (1) featuring an unprecedented skeleton, and angustifolimine (2) being a rare diamino Daphniphyllum alkaloid, were isolated from Daphniphyllum angustifolium. Their structures were elucidated by extensive spectroscopic analysis. The biosynthetic origin of 1 was postulated. Cytotoxic activities of 1 and 2 were tested, and all of them were inactive.

Structural modification of a specific antimicrobial lead against Helicobacter pylori discovered from traditional Chinese medicine and a structure-activity relationship study.

Psoralen (1a) was found to be a specific and potent antimicrobial lead against Helicobacter pylori (H. pylori) from a traditional Chinese medicine (TCM) in the bioassay directed isolation. A series of structurally diverse analogues of 1a were thus designed and synthesized to improve the antimicrobial potency, some of which showed more potent activities than the lead compound (1a) against H. pylori. Among them, compound 25a is 16-fold stronger (MIC = 0.39 µg/mL) than 1a (MIC = 6.25 µg/mL), and is even potent than the positive control metronidazole (MIC = 0.50 µg/mL). The in vitro antimicrobial activities against H. pylori of these structurally diverse analogues based on the scaffold of 1a have also led to an outline of structure-activity relationship.

Chuktabrins A and B, two novel limonoids from the twigs and leaves of Chukrasia tabularis.

Two novel limonoids, chuktabrin A (1), featuring the unique motifs of a 1,3-dioxolan-2-one and a 3,4-dihydro-2 H-pyran, and chuktabrin B (2), possessing an unprecedented polycyclic skeleton, were isolated from Chukrasia tabularis. The structures of 1 and 2 bearing a biosynthetically extended C3 and C2 unit at C-15, respectively, were elucidated on the basis of spectroscopic data, and that of 1 was confirmed by a single-crystal X-ray diffraction.

Structural elucidation of limonoids and steroids from Trichilia connaroides.

Six limonoids, trijugins D-H (1-5) and methyl 8alpha-hydroxy-8,30-dihydroangolensate (6), two degraded limonoids, trichiconnarins A and B (7-8), and a pregnane steroid, 3beta,4alpha-dihydroxypregnan-21-one (9), along with the known trijugin C (10) and 3beta,4alpha-dihydroxypregnan-16-one (11) were isolated from twigs and leaves of Trichilia connaroides. Their structures were established on the basis of extensive spectroscopic analysis.

Eucalyptals A-C with a new skeleton isolated from Eucalyptus globulus.

Eucalyptals A-C (1-3) with a new skeleton of 3,5-diformyl-isopentyl phloroglucinol-coupled cadinane were isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by spectroscopic analysis, and that of 1 was confirmed by single-crystal X-ray diffraction. The biosynthetic pathway of 1-3 was also postulated. Compounds 1-3 exhibited selective cytotoxicity against the HL-60 cell line.

Chuktabularins A-D, four new limonoids with unprecedented carbon skeletons from the stem bark of Chukrasia tabularis.

Chuktabularins A-D (1-4), four novel 16-norphragmalin-type limonoids that feature unprecedented skeletons with a biosynthetically extended C2 or C3 unit at C-15 forming a unique 2,7-dioxabicyclo[2.2.1]heptane moiety, were isolated from the stem bark of Chukrasia tabularis. Their structures were elucidated by spectroscopic analysis and computer modeling. The biosynthetic pathway of 1-4 was postulated.