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Abstract: A new method for the preparation of substituted dihydrobenzofurans is described. The p-alkenylphenols, mediated by cerium ammonium nitrate (CAN), undergo the oxidative dimerization to generate substituted dihydrobenzofurans including (±)-conocarpan, (±)-licarin A, (±)-acuminatin, as well as their related substituted dihydrobenzofurans. [Copyright &y& Elsevier]

Abstract: A novel synthesis of substituted 3,4-dihydroisoquinolin-1(2H)-ones is described. o-Oxiranylmethylbenzonitriles, prepared from isovanillin via five synthetic steps, were treated with NaCN/tetra-n-butylammonium bromide (TBAB) to yield 3,4-dihydroisoquinolin-1(2H)-ones in good yields. This one pot reaction demonstrates the novel and chemoselective nature of ring-opening of epoxide by cyanide to generate an iminoisochroman ring via cyclization, again ring-opening by cyanide to generate a Michael acceptor and a donor, and ring re-cyclization through an intramolecular conjugate addition. The detailed mechanism is also rationally proposed. [Copyright &y& Elsevier]

Abstract: Empirical evidences show that Japan-based companies moved their major operations to the USA due to the currency appreciation of Japanese Yen in 1980s. However, the multinational firms moving their operations abroad still face both the risk of foreign price and the risk of foreign exchange rate. According to the purchasing power parity (PPP) and interest rate parity (IRP), the foreign exchange rate has associations with the relative price and the relative interest rate between two countries. Therefore, when the price and the interest rate evolve stochastically as proposed by many scholars, we can anticipate the randomness of the foreign exchange rate. By integrating these three sources of risks as a hybrid uncertainty, we propose a framework for corporate valuation and investment strategy. We analytically derive corporate value for those multinationals in question and then numerically obtain the real option value by Monte Carlo simulations, based on which we investigate the optimal entry strategy. The sensitivity for corporate value, optimal entry time, and real option value are analyzed. The results suggest a decision support process for foreign investment timing strategy under the hybrid uncertainty. The managerial implication of this work is that the optimal investment strategy for the multinational firms with foreign operations depends on some market and risk factors, as well as correlations among them. [Copyright &y& Elsevier]

Abstract: A mild, efficient, and regioselective carbanion–yne intramolecular cyclization mediated by t-BuOK for the synthesis of 2-substituted 3-benzylbenzofurans is developed. It was started from o-iodophenol (1), based on O-alkylation, and the Sonogashira reaction in sequence to produce 2-(2-phenylethynylphenoxy)-1-arylalkanones (5). An intramolecular carbanion–yne 5-exo-dig cyclization reaction of 5, which was mediated by t-BuOK, yielded title benzofurans in good yields. [Copyright &y& Elsevier]

Abstract: We have shown that gypenosides (Gyp) induced cell cycle arrest and apoptosis in many human cancer cell lines. However, there are no reports showing that show Gyp acts on human leukemia HL-60 cells in vitro and in a murine xenograft model in vivo. In the present study effects of Gyp on cell morphological changes and viability, cell cycle arrest and induction of apoptosis in vitro and effects on Gyp in an in vivo murine xenograft model. Results indicated that Gyp induced morphological changes, decreased cell viability, induced G0/G1 arrest, DNA fragmentation and apoptosis (sub-G1 phase) in HL-60 cells. Gyp increased reactive oxygen species production and Ca2+ levels but reduced mitochondrial membrane potential in a dose- and time-dependent manner. Gyp also changed one of the primary indicators of endoplasmic reticulum (ER) stress due to the promotion of ATF6-α and ATF4-α associated with Ca2+ release. Gyp reduced the ratio of Bcl-2 to Bax due to an increase in the pro-apoptotic protein Bax and inhibited levels of the anti-apoptotic protein Bcl-2. Oral consumption of Gyp reduced tumor size of HL-60 cell xenograft mode mice in vivo. These results provide new information on understanding mechanisms by which Gyp induces cell cycle arrest and apoptosis in vitro and in vivo. [Copyright &y& Elsevier]

Abstract: Mild and environmentally benign methods for the syntheses of flavanones are described. The reaction of o-hydroxyacetophenones (1) and benzaldehydes (2) in water in the presence of DABCO at room temperature gave 3-hydroxy-1-(2-hydroxylphenyl)-3-arylpropan-1-ones (3a–i) as intermediates. Followed by an intramolecular dehydration of the 3a–i with the modified Mitsunobu’s reaction, the target flavanones (4a–i) were obtained. Moreover, the reaction of 1 and 2 at the same conditions but at reflux gave flavanones in one pot with good yields. [Copyright &y& Elsevier]

Abstract: In this paper, the degenerate kernels and Fourier series expansions are adopted in the null-field integral equation to solve the exterior Helmholtz problems with alluvial valleys. The main gain of using degenerate kernels in integral equations is free of calculating the principal values for singular integrals by locating the null-field point exactly on the real boundary. An adaptive observer system is addressed to fully employ the property of degenerate kernels for circular boundaries in the polar coordinate. Image concept and technique of decomposition are utilized for half-plane problems. After moving the null-field point to the real boundary and matching the boundary conditions, a linear algebraic system is obtained without boundary discretization. The unknown coefficients in the algebraic system can be easily determined. The present method is treated as a “semi-analytical” solution since error only attributes to the truncation of Fourier series. Earthquake analysis for the site response of alluvial valley or canyon subject to the incident SH-wave is the main concern. Numerical examples including single and successive alluvial valleys are given to test our program. Limiting cases of a single canyon and two successive canyons are also addressed. Amplification of soft basin is also observed in this study. The validity of the semi-analytical method is verified. Our advantages, well-posed model, principal value free, elimination of boundary-layer effect and exponential convergence and mesh-free, by using the present method are achieved. [Copyright &y& Elsevier]

Abstract: The present paper described how to establish a novel approach for various alkoxycyanonaphthalenes. It was started from isovanillin, and based on the Claisen rearrangement, O-alkylation, the Baylis–Hillman reaction, and ring-closing metathesis in sequence to produce the title compounds in good yield. [Copyright &y& Elsevier]

Epilepsy is a common neurological disorder affecting people of all ages, races and ethnic backgrounds world-wide. Vitamin B6 supplementation has been widely used as an adjuvant for treating epilepsy. However, the adverse effects, including nausea and peripheral sensory neuropathy, caused by long-term and high-dose consumption of vitamin B6 have undermined the usefulness of vitamin B6 supplementation, justifying additional experimental scrutiny of vitamin B6-associated toxicity. In the current study, we found that the presence of pyridoxine, the inactive form of B6 vitamer included in most nutrient supplements, increased the mortality of the larvae displaying chemical-induced epilepsy. The expression of leptin-b, one zebrafish ortholog of human leptin, was significantly increased in the larvae displaying seizures. Increased leptin-b expression alleviated larval seizure-like behavior when exposed to epilepsy inducer, but also increased larval mortality in the presence of pyridoxine. Meanwhile, elevated adam17 and mmp13 mRNA level were found in the larvae simultaneously exposed to epilepsy-inducer and pyridoxine. Adding TNF-α inhibitor and mmp13 inhibitor effectively improved the survival of larvae injected with leptin-b mRNA and exposed to pyridoxine subsequently. We conclude that increased leptin-b and metalloprotease expression contributed, at least partly, to the pyridoxine-associated toxicity observed in larvae displaying seizures. [ABSTRACT FROM AUTHOR]

Abstract: New syntheses of haginin E, equol, daidzein, and formononetin are described in this Letter. Through a sequence of a Wittig reaction, O-alkylation, and another Wittig reaction, 4-benzyloxysalicylaldehyde, which was prepared from resorcinol in two steps, was converted into the desired diene in one pot. Subsequently, the prepared diene was subjected to ring-closing metathesis using Grubbs’ catalyst (II) to construct the desired isoflavene intermediate. Using the prepared isoflavene, certain isoflavonoids such as haginin E, equol, daidzein, formononetin, and other related compounds were derived smoothly and in good overall yields. [Copyright &y& Elsevier]

This study aimed to select Bacillus spp. for surfactin production by solid-state fermentation and to investigate the physiochemical characterizations of the fermented product (FP) and its effect on growth performance, carcass trait, intestinal morphology, and clinical blood biochemistry of broilers. Accordingly, the correlations between the functional components of FP and the growth performance of broilers are elucidated. Four hundred eighty 1-day-old Ross 308 broiler chicks were randomly assigned to dietary supplementation of 2.5% fish meal, 2.5% unfermented product, or 2.5% FP produced by Bacillus subtilis LYS1 (LYS1), Bacillus amyloliquefaciens Da16, B. subtilis Lo6 (Lo6), B. subtilis NSN7, B. subtilis subsp. natto N21, or B. subtilis N12. Each treatment had 6 replicates. The experimental period was 5 wk. Results showed that the Lo6 showed the highest protease activity among all fermented groups. The LYS1 showed the highest surfactin yields (10.69 mg/g) among all fermented groups (P < 0.05). The weight gain (WG), feed conversion ratio (FCR), and production efficiency factor (PEF) of LYS1 group were significantly better than unfermented group at 0 to 3 and 0 to 5-wk-old (P < 0.05). The Bacillus -like counts and surfactin content of FP were moderately correlated to WG (0.7 > r > 0.3), FCR (-0.3 > r > -0.7), and PEF (0.7 > r > 0.3) at 0 to 3 and 0 to 5-wk-old (P < 0.05). The protease activity of FP was moderately correlated to WG (0.7 > r > 0.3), FCR (-0.3 > r > -0.7), and PEF (0.7 > r > 0.3) at 0 to 3-wk-old (P < 0.05). The villus height to crypt depth ratio in duodenum and jejunum of fish meal group and LYS1 group were higher than unfermented group (P < 0.05). In conclusion, LYS1 shows the highest surfactin yields. Diets supplemented with 2.5% LYS1 FP can improve the growth performance and the development of intestinal villi in broilers. Moreover, this study proves that the surfactin content, Bacillus -like counts, and protease activity of FP show a correlation to the growth performance of broilers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Doxorubicin, one of the original anthracyclines, remains among the most effective anticancer drugs ever developed. Clinical use of doxorubicin is, however, greatly limited by its serious adverse cardiac effects that may ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as ‘Danshen’ in traditional Chinese medicine for treating cardiovascular disorders. The objective of this study was set to evaluate the protective effect of tanshinone IIA on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). Methods: Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1μM), tanshinone IIA (0.1, 0.3, 1 and 3μM), or tanshinone IIA plus doxorubicin. Results: We found that tanshinone IIA (1 and 3μM) inhibited doxorubicin-induced reactive oxygen species generation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased BcL-xL expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, Akt phosphorylation was enhanced by tanshinone IIA treatment in cardiomyocytes. The wortmannin (100nM), LY294002 (10nM), and siRNA transfection for Akt significantly reduced tanshinone IIA-induced protective effect. Conclusions: These findings suggest that tanshinone IIA protects cardiomyocytes from doxorubicin-induced apoptosis in part through Akt-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin. [Copyright &y& Elsevier]

Abstract: Utilization of a novel carbanion-olefin intramolecular 6-endo-trig cyclization reaction to provide 2-aroyl-3,4-dihydro-2H-benzopyrans is described. Through a sequence of a Wittig reaction, O-alkylation, and carbanion-olefin intramolecular cyclization, salicylaldehydes were converted into a series of new 2-aroyl-3,4-dihydro-2H-benzopyrans in two steps or in one-pot reaction. [Copyright &y& Elsevier]

Cafestol, a diterpene molecule found in the berries of Coffea arabica L. (Rubiaceae), has been shown to exercise anti-angiogenic and anti-tumorigenic effects. However, cafestol's cellular mechanism has yet to be fully investigated. We previously demonstrated that urotensin II enhanced interleukin-8 secretion by endothelial cells, thereby increasing endothelial cell proliferation. Urotensin II may also participate in angiogenesis and tumor infiltration by macrophages. However, the effects of cafestol on urotensin II-induced interleukin-8 expression and cellular proliferation have not been determined. Here, we showed that pretreatment with cafestol inhibited urotensin II-stimulated endothelial cell proliferation. Further experiments demonstrated that cafestol increased translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and expression of enhanced heme oxygenase-1. Moreover, cafestol inhibited expression of urotensin II-induced interleukin-8. Cafestol's inhibitory effects on interleukin-8 expression and cellular proliferation induced by urotensin II were significantly abrogated by heme oxygenase-1 silencing, suggesting it may be involved in mediating the effects of cafestol. This study reports that cafestol inhibits urotensin II-induced interleukin-8 expression and cell proliferation via Nrf2/heme oxygenase-1-dependent mechanism in endothelial cells. These findings provide novel insight into the signaling pathways that may be important in mediating the effects of cafestol. [ABSTRACT FROM AUTHOR]

Objective When a cervical or thoracic benign intradural spinal tumor (BIST) coexists with lumbar degenerative diseases (LDD), diagnosis can be difficult. Symptoms of BIST-myelopathy can be mistaken as being related to LDD. Worse, an unnecessary lumbar surgery could be performed. This study was conducted to analyze cases in which an erroneous lumbar surgery was undertaken in the wake of failure to identify BIST-associated myelopathy. Methods Cases were found in a hospital database. Patients who underwent surgery for LDD first and then another surgery for BIST removal within a short interval were studied. Issues investigated included why the BISTs were missed, how they were found later, and how the patients reacted to the unnecessary lumbar procedures. Results Over 10 years, 167 patients received both surgeries for LDD and a cervical or thoracic BIST. In 7 patients, lumbar surgery preceded tumor removal by a short interval. Mistakes shared by the physicians included failure to detect myelopathy and a BIST, and a hasty decision for lumbar surgery, which soon turned out to be futile. Although the BISTs were subsequently found and removed, 5 patients believed that the lumbar surgery was unnecessary, with 4 patients expressing regrets and 1 patient threatening to take legal action against the initial surgeon. Conclusions Concomitant symptomatic LDD and BIST-associated myelopathy pose a diagnostic challenge. Spine specialists should refrain from reflexively linking leg symptoms and impaired ability to walk to LDD. Comprehensive patient evaluation is fundamental to avoid misdiagnosis and wrong lumbar surgery. [ABSTRACT FROM AUTHOR]

Abstract: The main purpose of this study is to investigate the coupled effects of the pulsatile blood flow in thermally significant blood vessels and the thermal relaxation time in living tissues on temperature distributions during thermal treatments. Considering the fact that propagation speed of heat transfer in solid tissues is actually finite according to experiments, the traditional Pennes bioheat transfer equation (PBTE) was modified to a wave bioheat transfer equation (WBTE) that contains both wave transportation and diffusion competing with each other and characterized by the thermal relaxation time. The wave behavior will be more dominant when the relaxation time is large. WBTE together with a coupled energy transport equation for blood vessel flow was used to describe the temperature evolution of our current tumor–blood vessel system, and the equations were numerically solved by the highly accurate multi-block Chebyshev pseudospectral method. Numerical results showed that temperature evolution from WBTE was quite different from their counterparts from PBTE due to the dominant wave feature under large relaxation time. For example, larger relaxation time would preserve high temperature longer and this effect is even more pronounced when heating is fast. It further implies that heat is drained more slowly when relaxation time is large, and would make thermal lesion region cover the tumor tissue, the heating target, better. This phenomenon would therefore hint that the traditional PBTE simulations might under-estimate the thermal dose exerted on tumor. As to the pulsation frequency of blood flow from heart beat which was originally predicted to be important here, it turned out that the thermal behavior is quite insensitive to pulsation frequency in the current study. [Copyright &y& Elsevier]

Abstract: Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨ m ), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G0/G1 phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G0/G1 phase arrest and triggered apoptosis in T24 cells. The down-regulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Bax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future. [Copyright &y& Elsevier]

Abstract: The synthesis of substituted 2-aroyl-3-methylchromen-4-one from isovanillin is described. O-Allylphenol (2) prepared from isovanillin (1) was allowed to react with various α-bromoacetophenone (3) to produce 2-(2-allyl-3,4-dimethoxy)phenoxy-1-aroylethanones (4). The resultant 4 were treated with 2equiv of potassium tert-butoxide to afford the substituted 2-aroyl-3-methylchromans (5) through an isomerization of an allylic double bond and a carbanion–olefin intramolecular 6-endo-trig cyclization reaction. Subsequently, resultant 5 were oxidized with DDQ to yield the title compound 6, in good over-all yields. [Copyright &y& Elsevier]

Abstract: The aim of this study is to investigate the feasibility of the heating on the tumor periphery by using high intensity focused ultrasound (HIFU) during thermal surgery. The pressure field induced by high intensity focused ultrasound transducer was solved by the Rayleigh–Sommerfeld diffraction integral. The temperature distribution was solved by the Pennes bioheat transfer equation. Numerical results show that even in the tumor periphery with high blood perfusion the thermal lesion can effectively cover the wanted therapeutic region for a rapid HIFU heating. The modality of heating on the tumor periphery by using high intensity focused ultrasound may provide an approach to eradication of a solid tumor with high blood perfusion in the periphery. [Copyright &y& Elsevier]