Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells.

Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C-E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 µM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

A new indole alkaloid from Cladosporium sp. SCSIO41205.

A new indole compound, N-hydroxy-N-(2-(1-hydroxy-2-methoxy-1H-indol-3-yl)ethyl acetamide (1), together with four known compounds, N-(2-(1H-indol-3-yl)ethylacetamide (2), N-acetylamicoumacin C (3), N-(2-phenylethyl)acetamide (4), and (2 R,3S)-1-(4-hydroxyphenyl)butane-2,3-diol (5) were isolated from Cladosporium sp. SCSIO41205. Their structures were established by detailed analysis of the NMR and HR-ESI-MS data.

Dankasterone A induces prostate cancer cell death by inducing oxidative stress.

Oxidative stress plays a dual role in tumor survival, either promoting tumor development or killing tumor cells under different conditions. Dankasterone A is a secondary metabolite derived from the fungus Talaromyces purpurogenu. It showed good potential in a screen for anti-prostate cancer compounds. In this study, MTT results showed dankasterone A was cytotoxic to prostate cancer cells, with an IC50 of 5.10 µM for PC-3 cells and 3.41 µM for 22Rv1 cells. Further studies, plate cloning assays and real-time cell analysis monitoring showed that dankasterone A significantly inhibited clonal colony formation and cell migration in 22Rv1 and PC-3 cells. In addition, flow cytometry results showed that dankasterone A induced apoptosis in prostate cancer cells while having no impact on cell cycle distribution. At the molecular level, Protein microarray experiments and western blot assays revealed that dankasterone A specifically and dramatically upregulated HO-1 protein expression; and the results of cell fluorescence staining showed that dankasterone A induced overexpression of reactive oxygen species in 22Rv1 and PC-3 cells. Taken together, dankasterone A induced prostate cancer cells to undergo intense oxidative stress, which resulted in the production of large amounts of HO-1 and the release of large amounts of reactive oxygen species, leading to apoptosis of prostate cancer cells, ultimately resulting in the inhibition of both cell proliferation and migration. We also validated the anti-prostate cancer effects of dankasterone A in vivo in a zebrafish xenograft tumor model. In conclusion, dankasterone A has the potential to be developed as an anti-prostate cancer drug.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038.

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.

Monitoring the Micro-Structural Evolution Mechanism of Next-Generation Ultra-High-Energy All-Nitrogen Materials: A Molecular Dynamic Study.

Micro-structural evolution mechanisms of next-generation ultra-high-energy all-nitrogen materials under the extreme conditions of high temperature coupled with high pressure were revealed by state-of-the-art ab initio molecular dynamics studies based on highest-nitrogen-content energetic material 2,2'-azobis(5-azidotetrazole). The results indicate that there are three primary initial uni-molecular decomposition pathways, namely, tetrazole ring opening, azido group elimination, and the breaking of the N-N bond between the azo group and azidotetrazole. In complicated global decomposition reactions, there exists the formation of nitrogen-rich clusters and all-nitrogen species. Lowering the temperature or increasing the pressure is conducive to increasing the N content in the nitrogen-rich cluster and widening the time distribution for the cluster. Abundant all-nitrogen species N4, N5, N6, N7, N8, N9, N10, and N13 were formed, and their detailed evolutionary process and construction mechanisms were enunciated. We innovatively constructed a series of next-generation ultra-high-energy all-nitrogen materials, which are expected to realize the controllable construction of next-generation ultra-high-energy all-nitrogen materials under extreme conditions.

Effects of Europium Complex on Thermal and Photoluminescence Properties of Polyurethane-Europium Materials.

A europium complex with double bonds was synthesized with crotonic acid as the ligand and a europium ion as the center ion. Then, the obtained europium complex was added to synthesized poly(urethane-acrylate) macromonomers to prepare the bonded polyurethane-europium materials by the polymerization of the double bonds in the complex and the poly(urethane-acrylate) macromonomers. The prepared polyurethane-europium materials had high transparency, good thermal stability and good fluorescence. The storage moduli of polyurethane-europium materials are obviously higher than those of pure polyurethane. Polyurethane-europium materials exhibit bright red light with good monochromaticity. The light transmittance of the material decreases slightly with increases in the europium complex content, but the luminescence intensity gradually increases. In particular, polyurethane-europium materials possess a long luminescence lifetime, which has potential applications for optical display instruments.

Phase transition-induced initial decomposition of nitrogen-rich binary CN compound 2,2'-azobis(5-azidotetrazole) and its precursor 2-amino-5-azidotetrazole via tetrazole ring opening under external electric fields: a comparative DFT-D study.

A comparative DFT-D study was performed to investigate the external electric field-induced crystal structures, electronic features, Hirshfeld surfaces, vibrational properties and initial decomposition mechanisms of nitrogen-rich binary CN compound 2,2'-azobis(5-azidotetrazole) (C2N16) and its precursor 2-amino-5-azidotetrazole (CH2N8). The results show that there exist phase transitions at the critical points of 0.006 a.u. and 0.008 a.u. for CH2N8 and C2N16, respectively, which are embodied in various properties of these compounds and induce their initial decomposition of the tetrazole ring opening via the breaking of N-N single bonds. The analysis of band gaps and density of states suggests the external electric field-induced enhancing ability for electron transition from the occupied orbitals to empty ones and N-N bond breaking may be the initial decomposition pathway for them. The variations in Hirshfeld surfaces indicate the spatial change and adjustment of non-bonding interactions in the two crystals. The discussions on vibrational properties indicate that IR characteristic peaks of all vibrational modes in the two crystals show a gradual red shift toward a low frequency region. The external electric field-induced initial decomposition pathways of both crystals are tetrazole ring opening via the breaking of a N-N single bond. Our findings provide insights for a comprehensive understanding of external electric field-induced phase transition and initial decomposition mechanisms of nitrogen-rich binary CN energetic compounds.

LncRNA NR120519 Blocks KRT17 to Promote Cell Proliferation and Migration in Hypopharyngeal Squamous Carcinoma.

BACKGROUND: Hypopharyngeal carcinoma is the worst type of head and neck squamous cell carcinoma. It is necessary to identify the key molecular targets related to the carcinogenesis and development of hypopharyngeal carcinoma. METHODS: Differentially expressed lncRNAs in hypopharyngeal carcinoma were selected by microarray, and lncRNA-associated proteins were found by RIP assay. Colony formation, CCK-8, wound healing and Transwell assays were performed to detect the effects of lncRNA and its associated protein on cell proliferation and migration in vitro. Downstream pathways of lncRNA and its associated protein were detected by WB. Through a subcutaneous tumor model, the effects of lncRNA and its associated protein on cell proliferation were detected. The expressions of lncRNA and its associated protein in hypopharyngeal cancer tissues were detected by qRT-PCR and immunohistochemistry assays, respectively, and survival analyses were performed by Kaplan-Meier curve. RESULTS: A total of 542 and 265 lncRNAs were upregulated and downregulated in microarrays, respectively. LncRNA NR120519 was upregulated and promoted cell proliferation and migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo. RIP and WB assays showed that KRT17 was associated with and blocked by NR120519.The silencing of KRT17 promoted cell proliferation and the migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo by activating the AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Finally, the NR120519 high expression and KRT17 low expression groups showed shorter overall survival. CONCLUSION: NR120519 activated the AKT/mTOR pathway and EMT by blocking KRT17 to promote cell proliferation and the migration of hypopharyngeal carcinoma.

Phase transition induced by an external electric field as a buffer to facilitate the initial decomposition of a series of catenated nitrogen energetic systems: a first-principles study.

The effect of an external electric field on the crystal and electronic structures, Hirshfeld surfaces, hydrogen-bonding network, mechanical properties, vibrational properties and initial decomposition mechanisms of a series of chain-catenated Nx (x = 4, 8, 10) energetic crystals was investigated via a first-principles study. The results indicate that the response behaviors to the external electric field show a great dependence on the nitrogen chain length and the intensity of the external electric field. The critical points of the phase transition were found and are embodied in various properties of all the compounds. Analysis of the electronic structures shows the increasing ability of the electron transition, thereby leading to possible subsequent decomposition reactions. The studies on Hirshfeld surfaces and the hydrogen-bonding network suggest that the external electric field can modify and tune the spatial distribution of the hydrogen-bonding network, thereby affecting the physicochemical properties. Our comprehensive analysis based on the mechanical properties, vibrational features and initial decomposition mechanism reveals that the external electric field can weaken the trigger bonds, reduce the thermal stability, and initiate decomposition. Our findings provide insights into the comprehensive understanding of the effects of an external electric field on energetic materials, especially for polynitrogen chain-catenated and even all-nitrogen compounds.

Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202.

Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3-11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC50 value of 1.31 µM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC50 value of 2.32 µM.

Azaphilones and Meroterpenoids from the Soft Coral-Derived Fungus Penicillium glabrum glmu003.

Two new azaphilone compounds, daldinins G (1) and H (2), together with nine known compounds daldinin D (3), sargassopenilline B (4), austalide V (5), austalide K (6), austalide P (7), austalide P acid (8), austalide H (9), 13-O-deacetyaustalide I (10), and 17-O-demethylaustalide B (11), were isolated from the soft coral-derived fungus Penicillium glabrum glmu003. The new structures of 1 and 2 were elucidated on the basis of 1D and 2D NMR, mass spectra, and electronic circular dichroism (ECD) data analysis. Compound 5 showed weak inhibitory activity against pancreatic lipase (PL) with IC50 value of 23.9 µg/mL.

Arthriniumsteroids A-D, four new steroids from the soft coral-derived fungus Simplicillium lanosoniveum SCSIO41212.

Four new steroids derivatives, namely arthriniumsteroids A - D (1-4), together with two known compounds, were isolated from the soft coral-derived fungus Simplicillium lanosoniveum SCSIO41212. Their structures were elucidated by spectroscopic analysis and by comparison with those reported in the literature. The absolute configuration of 2 was confirmed by single-crystal X-ray diffraction. In bioassay, all compounds showed weak inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells.

Ellagitannins and Oligomeric Proanthocyanidins of Three Polygonaceous Plants.

The aim of this study was to characterize hydrolyzable tannins in Polygonaceous plants, as only a few plants have previously been reported to contain ellagitannins. From Persicaria chinensis, a new hydrolyzable tannin called persicarianin was isolated and characterized to be 3-O-galloyl-4,6-(S)-dehydrohexahydroxydiphenoyl-d-glucose. Interestingly, acid hydrolysis of this compound afforded ellagic acid, despite the absence of a hexahydroxydiphenoyl group. From the rhizome of Polygonum runcinatum var. sinense, a large amount of granatin A, along with minor ellagitannins, helioscpoinin A, davicratinic acids B and C, and a new ellagitannin called polygonanin A, were isolated. Based on 2D nuclear magnetic resonance (NMR) spectroscopic examination, the structure of polygonanin A was determined to be 1,6-(S)-hexahydroxydiphenoyl-2,4-hydroxychebuloyl-ß-d-glucopyranose. These are the second and third hydrolyzable tannins isolated from Polygonaceous plants. In addition, oligomeric proanthocyanidins of Persicaria capitatum and P. chinensis were characterized by thiol degradation. These results suggested that some Polygonaceous plants are the source of hydrolyzable tannins not only proanthocyanidins.

Structurally diverse polyketides and phenylspirodrimanes from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201.

Four undescribed polyketide derivatives, named arthproliferins A-D (1-4), and one undescribed phenylspirodrimane derivative, named arthproliferin E (7), along with 11 known metabolites (5, 6, 8-16) were isolated from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201. Their structures were determined through spectroscopic methods, X-ray crystallography, and ECD analysis. Compounds 1 and 3-15 were evaluated for their cytotoxic, and antibacterial activities. Among them, compounds 1 and 15 displayed moderate inhibitory activity against methicillin-resistant Staphylococcus aureus ATCC 29213 with an MIC value of 78 and 39 µg/mL, respectively. Furthermore, compound 15 displayed strong cytotoxic activities against the tested cell line with IC50 values less than 39 nM.

Two new bioactive polyphenols from the soft coral-derived fungus Talaromyces sp. SCSIO 041201.

Two new polyphenols, talaversatilis A (1) and B (2), together with fifteen known compounds (3-17) were isolated from the extract of the culture broth of a soft coral-derived fungus Talaromyces sp. SCSIO 041201. The structures of these compounds were elucidated by the extensive analyses of spectroscopic data and by comparison with the reported literature. Antifouling and antibacterial activities of all purified compounds were tested and evaluated. Compounds 5 and 6 showed antifouling activity towards Bugula neritina larva, with LC50 values of 3.86 µg/mL and 3.05 µg/mL, respectively. Compounds 7, 8, 10 and 13 exhibited significant antibacterial activities against E. coli, MRSA, S. aureus and E. faecalis, with MIC values ranging from 0.45 to 15.6 µg/mL.

Synthesis, Morphology, and Luminescence Properties of Poly(urethane-acrylate) Nanowires Bonding with the Eu(III) Complex.

Photoluminescent poly(urethane-acrylate) (PUA) nanowires are designed and synthesized through copolymerization of a presynthesized-europium (Eu) complex with active vinyl groups and a vinyl functionalized PUA macromonomer matrix, initiated by azobisisobutyronitrile. This procedure provides a method to prepare PUA-Eu nanowires through in situ polymerization. Based on this, a series of PUA-Eu nanowires with diameters of 80-300 nm are successfully obtained in templates of anodized aluminum oxide by in situ polymerization. The obtained PUA-Eu nanowires display different morphologies such as sharp, round, and flat head by controlling the casting conditions. Furthermore, the PUA-Eu nanowires exhibit unique luminescence properties provided through Eu(III) elements, and the luminescence intensity significantly enhances with the increase in Eu complex concentration. PUA-Eu nanowires have longer fluorescence lifetimes than that of Eu complexes and PUA-Eu plates.

The proinflammatory cytokines IL-1ß and TNF-α modulate corneal epithelial wound healing through p16Ink4a suppressing STAT3 activity.

The proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) are involved in the corneal inflammatory response and wound healing following corneal injuries. However, the mechanism by which proinflammatory cytokines modulate corneal epithelial wound healing remains unclear. In this study, we found that IL-1ß or TNF-α was transiently elevated during corneal epithelial wound healing in mice. After corneal epithelial debridement, persistent treatment with IL-1ß or TNF-α restrained the level of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and boosted the level of cell cycle inhibitor p16Ink4a , resulting in impaired corneal epithelial repair. When p16Ink4a was deleted, the p-STAT3 level in corneal epithelium was enhanced and corneal epithelial wound healing was clearly accelerated. In diabetic mice, IL-1ß, TNF-α, and p16Ink4a appeared a sustained and strong expression in the corneal epithelium, and p16Ink4a knockdown partially reverted the defective diabetic corneal epithelial repair. Furthermore, immunoprecipitation proved that p16Ink4a interacted with p-STAT3 and thus possibly suppressed the STAT3 activity. Our findings revealed a novel mechanism that the proinflammatory cytokines modulate corneal epithelial wound healing via the p16Ink4a -STAT3 signaling.

Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201.

Penicildiones A-D (1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (5), stachybotrylactone B (6) and stachybotrin (7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 µmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 µmol·L-1.

IL-33/ST2 axis promotes the inflammatory response of nasal mucosal epithelial cells through inducing the ERK1/2 pathway.

Allergic rhinitis (AR) is a nasal mucosal inflammatory disease mediated by environmental allergens. At present, the relationship between the IL-33/ST2 axis, ERK1/2 pathway and AR progression needs further exploration. In our study, an AR model was constructed in vitro by treating HNEpC cells with Der p1. qRT-PCR was applied to assess the mRNA levels of IL-33, ST2, TNF-α, IL-6, and IL-8. Western blotting was used to measure the protein levels of IL-33, ST2, and the downstream proteins p-ERK1/2, ERK1/2, p-RSK, and RSK. IL-6, IL-8, IL-33, and TNF-α protein levels in cell supernatants were evaluated by ELISA. Flow cytometry was performed to check cell apoptosis of HNEpC in the presence or absence of Der p1. Our results indicate that the relative levels of IL-33, ST2, TNF-α, IL-6, and IL-8 were increased significantly in the AR model group. The above effects were notably reversed after transfection with shIL-33 or shST2. IL-33 stimulation further resulted in the increase in both ST2 and inflammation-associated cytokines, and these effects were restored after shST2 treatment. Also, the levels of inflammatory factors induced by IL-33 stimulation or ST2 overexpression were reversed after applying an ERK1/2 pathway blocker. In conclusion, IL-33/ST2 mediated inflammation of nasal mucosal epithelial cells by inducing the ERK1/2 pathway.