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Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (&minus, )-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3&beta, 5&alpha, diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 &mu, M, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (−)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3β,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F&ndash, L (1&ndash, 7). The chemical structures of 1&ndash, 7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1&ndash, 7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G (2) and cherbonolide H (3) displayed a more active effect than others on the inhibition of elastase release (48.2% &plusmn, 6.2%) and superoxide anion generation (44.5% &plusmn, 4.6%) at 30 &micro, M, respectively.

Chemical examination from the cultured soft coral Sarcophyton digitatum resulted in the isolation and structural identification of four new biscembranoidal metabolites, sardigitolides A&ndash, D (1&ndash, 4), along with three previously isolated biscembranoids, sarcophytolide L (5), glaucumolide A (6), glaucumolide B (7), and two known cembranoids (8 and 9). The chemical structures of all isolates were elucidated on the basis of 1D and 2D NMR spectroscopic analyses. Additionally, in order to discover bioactivity of marine natural products, 1&ndash, 8 were examined in terms of their inhibitory potential against the upregulation of inflammatory factor production in lipopolysaccharide (LPS)-stimulated murine macrophage J774A.1 cells and their cytotoxicities against a limited panel of cancer cells. The anti-inflammatory results showed that at a concentration of 10 &micro, g/mL, 6 and 8 inhibited the production of IL-1&beta, to 68 &plusmn, 1 and 56 &plusmn, 1%, respectively, in LPS-stimulated murine macrophages J774A.1. Furthermore, sardigitolide B (2) displayed cytotoxicities toward MCF-7 and MDA-MB-231 cancer cell lines with the IC50 values of 9.6 &plusmn, 3.0 and 14.8 &plusmn, 4.0 &micro, g/mL, respectively.

Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F&ndash, P (1&ndash, 11) of lobane&ndash, and prenyleudesmane&ndash, types, along with two known metabolites (12 and 13). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher&rsquo, s method. The complete assignment of 1H and 13C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1, 2, 4, 12, and 13. A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium.

Purpose The purpose of this paper is to examine the ethical investment willingness decision-making process to understand how investors evaluate corporate social responsibility (CSR) actions. Design/methodology/approach Data were collected through a survey of 298 individual investors and analyzed using structural equation modeling. Findings Results reveal that perfectionist decision-making style is positively related to perceived moral intensity, substitutability of financial returns, and ethical investment willingness. In addition, perceived moral intensity and substitutability of financial returns are positively related to ethical investment willingness. Finally, perceived moral intensity is positively related to substitutability of financial returns, and a two-factor causal mediation model is supported. Research limitations/implications The limitation of this study was that the pre-tests and sampling methods required all participants to have investing experience; however, procurement of trading information for each investor was impossible; thus, actual investment behaviors were undetermined. This study shed light on the mediating roles of perceived moral intensity and the substitutability of financial returns. Future studies can further investigate the factors influencing perceived moral intensity and the substitutability of financial returns. Practical implications Future ethical investment education can focus on cultivate the ability to distinguish ethical investments and change ethical investment willingness into actual investment behavior. Originality/value Understanding the relationship between these variables can help understand why ethical investment willingness varies among investors and how the traditional financial theory investment decision model should be revised as, internationally, more people have begun to observe CSR and sustainable development.

Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H-L (1-5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1-5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1-6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.

Yung-Ting Chang,1,2,* Chiung-Yao Huang,3,* Jen-Yang Tang,4,5 Chih-Chuang Liaw,1,3 Ruei-Nian Li,6 Jing-Ru Liu,6 Jyh-Horng Sheu,1,3,7,8 Hsueh-Wei Chang6,9–12 1Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan; 2Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, Taiwan; 3Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 8Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; 9Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; 10Cancer Center, Kaohsiung Medical University Hospital; Kaohsiung Medical University, Kaohsiung, Taiwan; 11Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 12Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan *These authors contributed equally to this work Abstract: We previously reported that the soft coral-derived bioactive substance, sinuleptolide, can inhibit the proliferation of oral cancer cells in association with oxidative stress. The functional role of oxidative stress in the cell-killing effect of sinuleptolide on oral cancer cells was not investigated as yet. To address this question, we introduced the reactive oxygen species (ROS) scavenger (N-acetylcysteine [NAC]) in a pretreatment to evaluate the sinuleptolide-induced changes to cell viability, morphology, intracellular ROS, mitochondrial superoxide, apoptosis, and DNA damage of oral cancer cells (Ca9-22). After sinuleptolide treatment, antiproliferation, apoptosis-like morphology, ROS/mitochondrial superoxide generation, annexin V-based apoptosis, and γH2AX-based DNA damage were induced. All these changes were blocked by NAC pretreatment at 4 mM for 1 h. This showed that the cell-killing mechanism of oral cancer cells of sinuleptolide is ROS dependent. Keywords: soft corals, oral cancer, N-acetylcysteine, oxidative stress, γH2AX&nbsp

Soft corals-derived natural product, sinularin, was antiproliferative against some cancers but its effect and detailed mechanism on oral cancer cells remain unclear. The subject of this study is to examine the antioral cancer effects and underlying detailed mechanisms in terms of cell viability, oxidative stress, cell cycle analysis, and apoptosis analyses. In MTS assay, sinularin dose-responsively decreased cell viability of three oral cancer cells (Ca9-22, HSC-3, and CAL 27) but only little damage to oral normal cells (HGF-1). This cell killing effect was rescued by the antioxidant N-acetylcysteine (NAC) pretreatment. Abnormal cell morphology and induction of reactive oxygen species (ROS) were found in sinularin-treated oral cancer Ca9-22 cells, however, NAC pretreatment also recovered these changes. Sinularin arrested the Ca9-22 cells at G2/M phase and dysregulated the G2/M regulatory proteins such as cdc2 and cyclin B1. Sinularin dose-responsively induced apoptosis on Ca9-22 cells in terms of flow cytometry (annexin V and pancaspase analyses) and western blotting (caspases 3, 8, 9) and poly (ADP-ribose) polymerase (PARP). These apoptotic changes of sinularin-treated Ca9-22 cells were rescued by NAC pretreatment. Taken together, sinularin induces oxidative stress-mediated antiproliferation, G2/M arrest, and apoptosis against oral cancer cells and may be a potential marine drug for antioral cancer therapy.

Two new capnosane-based diterpenoids, flaccidenol A (1) and 7-epi-pavidolide D (2), two new cembranoids, flaccidodioxide (3) and flaccidodiol (4), and three known compounds 5 to 7 were characterized from the marine soft coral Klyxum flaccidum, collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus Klyxum for the first time. The cytotoxicity of compounds 1 to 7 against the proliferation of a limited panel of cancer cell lines was assayed. The isolated diterpenoids also exhibited anti-inflammatory activity through suppression of superoxide anion generation and elastase release in the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-stimulated human neutrophils. Furthermore, 1 and 7 also exhibited cytotoxicity toward the tested cancer cells, and 7 could effectively inhibit elastase release. It is worth noting that the biological activities of 7 are reported for the first time in this paper.

Chemical investigation of the red alga Laurencia tristicha led to the discovery of eight new halogenated chamigrane-type sesquiterpenoids (1-8) and one new bromocuparane-type sesquiterpene (9), along with nine known related metabolites (10-18). Their structures were elucidated on the basis of extensive spectroscopic analyses, and the absolute configurations of 1-8 were proposed by comparison to the biosynthetically related known compound 12. Cytotoxicity, antibacterial, and anti-inflammatory activities of these isolates were also investigated. The results showed that compound 11 exhibited good antibacterial activity against Serratia marcescens compared to the positive control ampicillin at a dosage of 100 μg/disk. Compound 17 showed strong inhibition toward elastase release generation at 10 μM.

Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed that 4 exhibited inhibition activity against the growth of HT-29, P388 and K562 cancer cell lines, whereas 2 showed selective cytotoxicity toward P388 cells. Compound 4 was also found to display significant anti-inflammatory activity for suppressing superoxide anion generation (O2(-)) and elastase release.

The environmental pollution caused by Advanced Semiconductor Engineering in October 2013 in Taiwan highlighted the fact that foreign investors tend to support the classical economic ideas of arbitrage and shareholder wealth maximization, which is in conflict with the fact that institutional investors in the current global capital market lean towards the stakeholder theory in ethical investments. Will local investors’ decision-making also be influenced by differences in the perceived ethics of negative environmental corporate social responsibility (ECSR)? Compared to the remedial measures implemented by British Petroleum for the 2010 Deepwater Horizon oil spill, Advanced Semiconductor Engineering, another international corporation, decided to not respond to any news regarding the toxic wastewater incident. In contrast, Advanced Semiconductor Engineering only made clearer promises after extreme public pressure. This study investigated whether remedial measures for negative ECSR are an important factor influencing investors’ decisions. The purpose is to clarify the interactions among perceived moral intensity of negative ECSR, the implementation of remedial measures, and the intention of ethical investment. An experimental design was employed to test the hypotheses. The results indicated that perceived moral intensity has a significant negative impact on the intention of ethical investment. The implementation of remedial measures for negative ECSR affects investors’ intent to invest. Finally, positive ECSR remedial measures also serve as a key moderating variable in the relationship between perceived moral intensity and the intention of ethical investment. This study clarified whether the provision of remedial mechanisms can effectively recover or maintain investor investment intent when companies experience negative ECSR.

Continuous chemical investigation of the soft coral Klyxum molle resulted in the isolation of six new eunicellin-derived diterpenoids, klymollins Y ( 1 ), Z ( 2 ), and klyxumollins A–D ( 3 – 6 ), together with two known compounds ( 7 and 8 ). The planar structures and relative configurations of these new compounds were elucidated by MS, 1D and 2D NMR experiments. Klyxumollins C ( 5 ) represents the first 6,7-secoeunicellin possessing an ester group at C-6 and 6 is the first eunicellin comprising with an aromatic ether linkage. Anti-inflammatory and cytotoxic activities of the isolates were reported.

The peroxisome proliferator-activated receptor &gamma, (PPAR&gamma, ) is a nuclear receptor that plays a key role in regulating cellular metabolism, and is a therapeutic target for cancer therapy. To search for potential PPAR&gamma, activators, a compound library comprising 11 marine compounds was examined. Among them, a sterol, 3&beta, 11-dihydroxy-9,11-secogorgost-5-en-9-one (compound 1), showed the highest PPAR&gamma, activity with an IC50 value of 8.3 &mu, M for inhibiting human breast adenocarcinoma cell (MCF-7) growth. Western blotting experiments showed that compound 1 induces caspase activation and PARP cleavage. In addition, compound 1 modulated the expression of various PPAR&gamma, regulated downstream biomarkers including cyclin D1, cyclin-dependent kinase (CDK)6, B-cell lymphoma 2 (Bcl-2), p38, and extracellular-signal-regulated kinase (ERK). Moreover, compound 1 increased reactive oxygen species (ROS) generation, upregulated the phosphorylation and expression of H2AX, and induced autophagy. Interestingly, pre-treatment with the autophagy inhibitor 3-methyladenine rescued cells from compound 1-induced growth inhibition, which indicates that the cytotoxic effect of compound 1 is, in part, attributable to its ability to induce autophagy. In conclusion, these findings suggest the translational potential of compound 1 in breast cancer therapy.

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A&ndash, C (1&ndash, 3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7&ndash, 16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells.

Hepatitis C virus (HCV) chronically infects 2–3% people of the global population, which leads to liver cirrhosis and hepatocellular carcinoma. Drug resistance remains a serious problem that limits the effectiveness of US Food and Drug Administration (FDA)-approved direct-acting antiviral (DAA) drugs against HCV proteins. The objective of our study was to discover new antivirals from natural products to supplement current therapeutics. We demonstrated that lobohedleolide, isolated from the Formosan soft coral Lobophytum crassum, significantly reduced HCV replication in replicon cells and JFH-1 infection system, with EC50 values of 10 ± 0.56 and 22 ± 0.75 μM, respectively, at non-toxic concentrations. We further observed that the inhibitory effect of lobohedleolide on HCV replication is due to suppression of HCV-induced cyclooxygenase-2 (COX-2) expression. Based on deletion-mutant analysis of the COX-2 promoter, we identified CCAAT/enhancer-binding protein (C/EBP) as a key transcription factor for the down-regulation of COX-2 by lobohedleolide, through which lobohedleolide decreased the phosphorylation of c-Jun NH2-terminal protein kinase and c-Jun to suppress HCV-induced C/EBP expression. The combination treatment of lobohedleolide with clinically used HCV drugs synergistically reduced HCV RNA replication, indicating that lobohedleolide exhibited a high biomedical potential to be used as a supplementary therapeutic agent to control HCV infection.

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

Two new tocopherol-derived metabolites, hirsutocospiro A (1) and hirsutocoquinone A (2), were isolated from the soft coral Cladiella hirsuta. The structures of 1 and 2 were determined by extensive spectroscopic analysis. The in vitro anti-inflammatory activity of compounds 1 and 2 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils. Compound 1 was shown to exhibit significant anti-inflammatory activity.

Two new pregnane glycosides, hirsutosterosides A and B (1 and 2), as well as two new α-tocopherylhydroquinone glycosides, cladophenol glycosides A and B (3 and 4) were isolated from a soft coral Cladiella hirsuta. In addition, a new steroidal glycoside, lobatasteroside A (5) along with six known steroids (6–11), were discovered from the other soft coral Sinularia nanolobata. Their structures were elucidated by extensive spectroscopic analysis. Cytotoxicities of the isolates against a limited panel of cancer cell lines were reported. The inhibitory activities for superoxide anion generation and elastase release for these compounds were also examined to evaluate the anti-inflammatory potential.

A known withanolide steroid cilistol G (1) and six new withanolides, capsisteroids A–F (2–7), were isolated from the EtOAc extract of the leaves of Solanum capsicoides. The structures of compounds 1–7 were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). The structure of 1 was further confirmed by a single-crystal X-ray diffraction analysis. These compounds were found not to be cytotoxic toward a limited panel of cancer cell lines. Further, the anti-inflammatory activity of compounds 1–7 was studied by measuring their ability to suppress superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils.

A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica, which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1 possesses a β-D-xylopyranose. The structures of the new compounds were elucidated on the basis of spectroscopic analyses. The cytotoxicities of compounds 1–4 against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of these new compounds 1–4 were also evaluated by measuring their ability to suppress superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. Compounds 2 and 3 were shown to exhibit significant cytotoxicity, and compounds 3 and 4 were also found to display attracting anti-inflammatory activities.

Five new isoprenoids, 3,4,8,16-tetra-epi-lobocrasol (1), 1,15β-epoxy-deoxysarcophine (2), 3,4-dihydro-4α,7β,8α-trihydroxy-Δ2-sarcophine (3), ent-sarcophyolide E (4), and 16-deacetyl- halicrasterol B (5) and ten known compounds 6‒15, were characterized from the marine soft coral Sarcophyton glaucum, collected off Taitung coastline. Their structures were defined by analyzing spectra data, especially 2D NMR and electronic circular dichroism (ECD). The structure of the known compound lobocrasol (7) was revised. Cytotoxicity potential of the isolated compounds was reported, too.

New cembranoids klyflaccicembranols A–I (1–9), along with gibberosene D (10), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, and spectral data comparison with related structures. The cytotoxicity of the isolated metabolites, as well as their nitric oxide (NO) inhibitory activity, were evaluated and reported. Metabolites 2, 4, 6, 8 and 9 were found to exhibit variable activities against a limited panel of cancer cell lines in a range of IC50 16.5–49.4 μM. Among the tested cembranoids, compounds 4, 5, 6, and 9 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages at a dose of 50 μg/mL.

Soft corals-derived natural product, sinularin, was antiproliferative against some cancers but its effect and detailed mechanism on oral cancer cells remain unclear. The subject of this study is to examine the antioral cancer effects and underlying detailed mechanisms in terms of cell viability, oxidative stress, cell cycle analysis, and apoptosis analyses. In MTS assay, sinularin dose-responsively decreased cell viability of three oral cancer cells (Ca9-22, HSC-3, and CAL 27) but only little damage to oral normal cells (HGF-1). This cell killing effect was rescued by the antioxidant N-acetylcysteine (NAC) pretreatment. Abnormal cell morphology and induction of reactive oxygen species (ROS) were found in sinularin-treated oral cancer Ca9-22 cells, however, NAC pretreatment also recovered these changes. Sinularin arrested the Ca9-22 cells at G2/M phase and dysregulated the G2/M regulatory proteins such as cdc2 and cyclin B1. Sinularin dose-responsively induced apoptosis on Ca9-22 cells in terms of flow cytometry (annexin V and pancaspase analyses) and western blotting (caspases 3, 8, 9) and poly (ADP-ribose) polymerase (PARP). These apoptotic changes of sinularin-treated Ca9-22 cells were rescued by NAC pretreatment. Taken together, sinularin induces oxidative stress-mediated antiproliferation, G2/M arrest, and apoptosis against oral cancer cells and may be a potential marine drug for antioral cancer therapy.

Five new eunicellin-based diterpenoids, krempfielins E–I (1–5) and seven known compounds (6–12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

New eunicellin-base diterpenoids, hirsutalins I–M (1–5), were isolated from the soft coral Cladiella hirsuta. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configuration of 2 was determined by Mosher's method. These compounds did not exhibit cytotoxicity toward a limited panel of cancer cell lines but showed nitric oxide inhibitory activity in LPS-stimulated RAW264.7 macrophage cells. Among them, compound 3 was found to possess the strongest NO inhibitory activity with an IC50 value of 9.8 μg/mL. Furthermore, 3 was shown to significantly reduce the expression iNOS protein in the same cells.

This study focuses on the design and fabrication of a planar rotary electromagnetic energy harvester with a low rotary speed for bicycle dynamos. The primary components of a dynamo system include planar multilayer and multipole coils, a soft magnet (iron) used to enhance magnetic efficiency, and a multipole Nd/Fe/B (neodymium, iron, and boron) permanent magnet. Finite element analysis and the Taguchi method were used to design this dynamo system. The optimal parameters of the magnet, coil, and soft magnet were determined by using the Taguchi method. Low temperature co-fired ceramics (LTCC) technology was applied to fabricate silver planar multilayer coils with 10 and 20 layers, respectively. Nd/Fe/B was sintered to obtain the desired characteristics of a permanent magnet. A 28-pole magnet Nd/Fe/B with an outer diameter of 50 mm and a thickness of 2 mm was also sintered and magnetized, creating a magnetic field of 1.4 T. Simulation results show that a harvester with 20-layer and 22 poles coils, a linewidth of 200 μm, an interspace of 100 μm, and a layer thickness of 40 μm can generate voltages of 1.796 V at a rotary speeds of 300 rpm. This harvester system was approximately 50 mm × 50 mm × 3 mm in volume (including 20-layer micro-coils + magnet + spacing between the coil and magnet surface). The experimentally induced voltages of 20-layer coils were 1.539 V. Measurements show a similar trend with finite element simulations. The power output was 0.788 mW with an external resistance load of 737 Ω. This harvester is capable of powering 200 LEDs (forward voltage (VF)

New steroids, klyflaccisteroids K-M (1-3), were isolated from a soft coral Klyxum flaccidum. Their structures were elucidated on the basis of extensive spectroscopic analysis. Klyflaccisteroid K (1) is the unique 9,11-secosteroid with a 5,8-epidioxy-9-ene functional group. Klyflaccisteroid L (2) has an unusual 11-norsteroid skeleton and is the first example of 11-oxasteroid isolated from natural sources. Cytotoxicity assay showed that 1 and 3 possessed moderate to weak cytotoxicity against these cancer cells. Compound 1 was also found to display significant anti-inflammatory activity of suppressing superoxide anion generation (O2-) and elastase release, and compound 3 was found to show notable anti-inflammatory activity toward inhibition of elasstase release, too.

Four new steroids, klyflaccisteroids G—J, are isolated and evaluated for their biological activity.

Three new steroids, petasitosterones A and B (1 and 2) and a spirosteroid petasitosterone C (3), along with eight known steroids (4–11), were isolated from a Formosan marine soft coral Umbellulifera petasites. The structures of these compounds were elucidated by extensive spectroscopic analysis and comparison of spectroscopic data with those reported. Compound 3 is a marine steroid with a rarely found A/B spiro[4,5]decane ring system. Compounds 1–3 and 5 displayed inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas 2 and 5 exhibited significant anti-inflammatory activity to inhibit nitric oxide (NO) production. The inhibitory activities for superoxide anion generation and elastase release of compounds 1–11 were also examined to evaluate the anti-inflammatory potential, and 2–4 were shown to exhibit significant activities.

Method of balanced scorecard (BSC) may well be one of the most popular strategy management and performance management systems, but BSC can only really success if it is appropriately linked to the employees' intrinsic and extrinsic incentives. In this research, two central issues include motivation and effect on long-term firm value comes into focus in the context of performance evaluation and compensation schemes - the central concern of this study. Yet, few studies have explored dynamic firm value evaluation and integrated it with optimal weighted in a performance compensation system in accordance with their forward-looking long-term firm value. This gap in the literature is striking - not only as it sits in stark contrast to the extensive studies on equity valuations, but also as interpretations for the effect of optimal weight for performance rewards on enhancing long-term firm value through increase existing motivation. It is important because the determined compensation relative weights of individual four perspectives influences the employees' incentive to work performance in the interest of the organization's strategic objective fulfillment.

Four new isoprenoids, including two norcembranoids sinulerectols A and B (1 and 2), a cembranoid sinulerectol C (3), and a degraded cembranoid sinulerectadione (4), along with three known isoprenoids, an unnamed norcembrene (5), sinularectin (6), and ineleganolide (7), and a known nitrogen-containing compound (Z)-N-[2-(4-hydroxyphenyl)ethyl]-3-methyldodec-2-enamide (8), were isolated from an extract of the marine soft coral Sinularia erecta. The structure of sinularectin (6) was revised, too. Compounds 3, 4, and 8 exhibited inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas 1, 2, and 8 displayed potent anti-inflammatory activity in fMLP/CB-stimulated human neutrophils.

Continuous chemical investigation of the soft coral Klyxum molle resulted in the isolation of six new eunicellin-derived diterpenoids, klymollins Y ( 1 ), Z ( 2 ), and klyxumollins A–D ( 3 – 6 ), together with two known compounds ( 7 and 8 ). The planar structures and relative configurations of these new compounds were elucidated by MS, 1D and 2D NMR experiments. Klyxumollins C ( 5 ) represents the first 6,7-secoeunicellin possessing an ester group at C-6 and 6 is the first eunicellin comprising with an aromatic ether linkage. Anti-inflammatory and cytotoxic activities of the isolates were reported.

Two new pregnane glycosides, hirsutosterosides A and B (1 and 2), as well as two new α-tocopherylhydroquinone glycosides, cladophenol glycosides A and B (3 and 4) were isolated from a soft coral Cladiella hirsuta. In addition, a new steroidal glycoside, lobatasteroside A (5) along with six known steroids (6–11), were discovered from the other soft coral Sinularia nanolobata. Their structures were elucidated by extensive spectroscopic analysis. Cytotoxicities of the isolates against a limited panel of cancer cell lines were reported. The inhibitory activities for superoxide anion generation and elastase release for these compounds were also examined to evaluate the anti-inflammatory potential.

Chemical investigations on the EtOAc-soluble fractions from the EtOH extract of Formosa soft coral afforded a new 9,11-secosteroid, 8αH-3β,11-dihydroxy-5α,6α-expoxy-24-methylene-9,11-secocholestan-9-one (1), along with one known steroid 3β,11-dihydroxy-5β,6β-expoxy-24-methylene-9,11-secocholestan-9-one (2) from Sinularia granosa. The structure of the new metabolite was elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with the known compounds, including 2. Both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and 1 also was found to effectively reduce the level of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells at 10 μM. Furthermore, cytotoxic activity of 1 and 2 toward a limited panel of cancer cell lines was also discovered.

Two new cadinane-type sesquiterpenoids, scabralins A (1) and B (2) were obtained from the soft coral Sinularia scabra. Metabolite 1 was shown to exhibit moderate to weak cytotoxicity against MCF-7, WiDr, Daoy, and HEp 2 cancer cell lines. Also, incubation with 10 µM compound 1 significantly inhibited the accumulation of the pro-inflammatory inducible nitric oxide synthase protein in lipopolysaccharide-stimulated RAW264.7 macrophage cells.

Three new cembranoids, sarcocrassocolides M–O (1–3), have been isolated from the soft coral Sarcophyton crassocaule. The structures of the metabolites were determined by extensive spectroscopic analysis. Compounds 1–3 were shown to exhibit moderate cytotoxicity toward a limited panel of cancer cell lines and display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.

One new sterol, crassarosterol A (1), and four new steroidal glycosides, crassarosterosides A–D (2–5) were isolated from the Formosan soft coral Sinularia crassa. The absolute configuration of 1 was determined using the Mosher’s method. The absolute configurations for the sugar moieties of 2–5 were determined by HPLC analysis on the o-tolylthiocarbamates derived from the liberated sugar after acid hydrolysis. Compounds 2 and 4 could significantly inhibit the expression of pro-inflammatory iNOS protein at 10 µM. In contrast, 1–3 were found to stimulate the expression of COX-2 protein at this concentration. Steroids 1 and 4 also showed cytotoxicity toward the selected human liver cancer cells.

Seven new diterpenoids, namely, flexibilisolides C–G ( 1 – 5 ), flexibilisin C ( 6 ), and a novel 11,12-secoflexibillin ( 7 ), along with seven known compounds, 8 – 14 , were isolated from the Dongsha Atoll soft coral Sinularia flexibilis . The structures of the new metabolites were elucidated by extensive spectroscopic analysis and comparison of the NMR data with those of known analogues. Compounds 1 , 8 , and 11 were shown to exhibit moderate cytotoxic activity against HeLa and B16 cancer cell lines, and compound 10 was found to exhibit more potent cytotoxic activity against SK-Hep1 and B16 cancer cell lines. Moreover, compounds 1 , 2 , 8 , 9 , and 11 – 14 could significantly inhibit the accumulation of the pro-inflammatory iNOS protein and 1 , 8 , 11 , and 14 could reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

Glaucumolides A (1) and B (2), novel biscembranes composed of an unprecedented α,β-unsaturated ε-lactone, along with the known metabolites ximaolide A (3) and isosarcophytonolide D (4), were isolated from the cultured soft coral Sarcophyton glaucum. The structures of the new metabolites were determined by extensive spectroscopic analyses. Compounds 1 and 2 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. In anti-inflammation assay, compounds 1 and 2 displayed strong inhibition of superoxide anion generation and elastase release in human neutrophils stimulated by fMLP/CB. Furthermore, both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein and compounds 1−3 were found to effectively reduce the expression of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells.

New eunicellin-based diterpenoids, klysimplexins U–X (1–4), were isolated from a cultured soft coral Klyxum simplex. Their structures were elucidated by spectroscopic methods, particularly in 1D an...

Eight new cembranoids, crassarines A–H (1–8) were isolated from the Formosan soft coral Sinularia crassa. Compounds 1–3 represent the rare cembranoids with a 1,12-oxa-bridged tetrahydrofuran ring, while 4 and 5 are the firstly discovered 1,11-oxa-bridged tetrahydropyranocembranoids. The absolute configuration of 6 was determined using the Mosher’s method. Compounds 6 and 8 were found to significantly inhibit the expression of both pro-inflammatory iNOS and COX-2 proteins at 10 µM, respectively, while compounds 4–8 were found to be non-cytotoxic toward the selected human liver cancer cells.

Five new nardosinane-type sesquiterpenoids, paralemnolins Q–U (1–5), along with three known compounds (6–8), were isolated from the Formosan soft coral Paralemnalia thyrsoides. The structures of new metabolites were elucidated on the basis of extensive spectroscopic methods, and the absolute configuration of 1 was determined by the application of Mosher’s method on 1. Among these metabolites, 1 and 3 are rarely found nardosinane-type sesquiterpenoids, possessing novel polycyclic structures. Compounds 1, 3, 6 and 7 were found to possess neuroprotective activity.

Six new eunicellin-based diterpenoids, simplexins J–O (1–6), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectrosco...

Two new natural products, the oppositane-type sesquiterpenoids leptocladolins A and B (1 and 2), along with two known compounds 1β-hydroxy-6α-acetoxyeudesm-4(15)-ene (3) and 1β,6α-dihydroxyeudesm-4...

Two new sesquiterpenoids, sinularioperoxide E (1), ethyl 5-[(2′S,5′E)-2′, 6′-dimethylocta-5′,7′-dienyl]furan-3-carboxylate (3), and a new C11 terpenoid-related carboxylic acid, (3S,6E)-3,7-dimethyl-nona-6,8-dienoic acid (2) were isolated from a Formosan soft coral Sinularia sp. The structures of 1-3 were elucidated on the basis of extensive spectroscopic analyses and by comparison of the spectral data with those of the related metabolites.

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Mosher's method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Sinuleptolide, a soft corals-derived bioactive norditerpenoid, is a marine natural product with a potent anti-inflammatory effect. We evaluate the potential anti-oral cancer effects of sinuleptolide and investigate the possible mechanisms involved.Cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and DNA damage analyses were performed.In a cell viability assay, we found that sinuleptolide is dose-responsively antiproliferative against oral gingival cancer Ca9-22 cells but less harmful to normal human gingival fibroblast (HGF-1) cells (P0.001). In cell cycle analysis, sinuleptolide induced subG1 accumulation at a higher dose and led to G2/M arrest of Ca9-22 cells (P0.005). Apoptosis was significantly increased in sinuleptolide-treated Ca9-22 cells based on annexin V and poly(ADP-ribose) polymerase (PARP) expressions (P0.05-0.0001). Based on flow cytometer analysis, sinuleptolide also induced the generation of ROS and decreased MMP in a dose-responsive manner (P0.05-0.0001). DNA damage increased dose-responsively after sinuleptolide treatments (P0.001) based on comet and γH2AX assays.Sinuleptolide can induce an antiproliferation of oral cancer Ca9-22 cells involving apoptosis, oxidative stress and DNA damage, suggesting that sinuleptolide represents a potential chemotherapeutic drug for oral cancer treatment.

New eunicellin-type hirsutalins N–R (1–5), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds 1–7 against the proliferation of a limited panel of cancer cell lines was measured. The in vitro anti-inflammatory activity of compounds 1–7 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils.