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Background Magnesium-loaded hydroxyapatite (Mg@HAp) is a potential biomaterial for bone healing application but has not been comprehensively synthesized yet. Methods In this study, we utilize phosphatidylcholine (PC)-assisted method for synthesizing Mg@HAp with controllable Mg amount from 1.44 to 10.64 wt%. It is proposed that the negatively charged phosphate functional group of PC could act on cations (i.e. Mg2+ or Ca2+), which provides stable nucleation for the formation of Mg@HAp. Significant findings By optimizing the synthesis conditions, we successfully prepared a Mg@HAp with a relatively low crystallinity which is similar to human bone structure, as evidenced by XRD measurement. The in vitro test of bone cells (MG-63) shows that the release of Mg2+ ions from Mg@HAp enhances cellular proliferation and differentiation. We believe the synthesized Mg@HAp would be a promising biomaterial in orthopedic applications.

Steroids have been shown to be beneficial in patients and mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection; however, the mechanism for this beneficial effect is unknown. We speculated that the effect of steroids in eosinophilic meningitis caused by A. cantonensis infection may be mediated by the downregulation of matrix metallopeptidase-9 (MMP-9) and oxidative stress pathways via glucocorticoid receptors (GRs). We found blood–brain barrier (BBB) dysfunction in mice with eosinophilic meningitis 2–3 weeks after infection as evidenced by increased extravasation of Evans blue and cerebrospinal fluid (CSF) albumin levels. The administration of dexamethasone significantly decreased the amount of Evans blue and CSF albumin. The effect of dexamethasone was mediated by GRs and heat shock protein 70, resulting in subsequent decreases in the expressions of nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in the CSF and brain parenchymal after 2 weeks of steroid administration. Steroid treatment also decreased CSF/brain homogenate MMP-9 concentrations, but had no effect on CSF MMP-2 levels, indicating that MMP-9 rather than MMP-2 played a major role in BBB dysfunction in mice with eosinophilic meningitis. The concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) gradually increased after 1–3 weeks of infection, and the administration of dexamethasone significantly downregulated the concentration of oxidized derivative 8-OHdG in CSF. In conclusion, increased 8-OHdG and MMP-9 concentrations were found in mice with eosinophilic meningitis caused by A. cantonensis infection. The effect of dexamethasone was mediated by GRs and significantly decreased not only the levels of 8-OHdG and MMP-9 but also NF-κB, JNK and ERK.

Two bipolar hosts, 8-cbzBIFP and 10-cbzBIFP, both with basic skeletons of orthogonally-connected carbazole and benzimidazo〈1,2-f〉phenanthridine (BIFP) have been prepared. The planar structure of the BIFP moiety governs the molecular stacking in the crystal lattice. Electron transport properties, in comparison to the benzimidazole derivatives, are facilitated. Both hosts display fabulous performances in phosphorescent organic light-emitting diodes with bis(2-phenylpyridine)(acetylacetonate)iridium(III) as an emitter. The optimized green PhOLED of 10-cbzBIFP achieves the maximum brightness (Lmax) of 58 810 cd m−2, the maximum current efficiency (ηc) of 87.0 cd A−1 and external quantum efficiency (EQE) of 21.1%. Likewise, 8-cbzBIFP shows an Lmax of 58 870 cd m−2, ηc of 77.3 cd A−1 and EQE of 19.1%.

This paper describes a concise, easy-operation, high-yielding method for the synthesis of 3-sulfonyl-2-aryl-2H-chromenes by a one-pot, straightforward two-step synthetic route, which includes (i) Cu(OAc)2/PyBOP-mediated intermolecular [4+2] annulation of substituted salicylic acids with β-sulfonylstyrenes in the presence of DMAP in refluxing DMF, and (ii) sequential O-alkylation of the resulting sulfonylflavanones with n-butyl bromide. A plausible mechanism is proposed and discussed. This protocol provides a highly effective annulation via one carbon–oxygen (C–O) and one carbon–carbon (C–C) bond formations.

In this novel study, we isolated 28 compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on a bioassay-guided procedure and also discovered the possible matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) modulatory effect of pheophorbide A (PA). To evaluate the regulatory activity on MMP-2 and MMP-9, the HT-1080 human fibrosarcoma cells were treated with various concentrations of extracted materials and isolated compounds. PA was extracted by methanol from the leaves of A. sinensis and separated from the fraction of the partitioned ethyl acetate layer. PA is believed to be an active component for MMP expression since it exhibited significant stimulation on MMP-2 and proMMP-9 activity. When treating with 50 μM of PA, the expression of MMP-2 and MMP-9 were increased 1.9-fold and 2.3-fold, respectively. PA also exhibited no cytotoxicity against HT-1080 cells when the cell viability was monitored. Furthermore, no significant MMP activity was observed when five PA analogues were evaluated. This study is the first to demonstrate that C-17 of PA is the deciding factor in determining the bioactivity of the compound. The MMP-2 and proMMP-9 modulatory activity of PA indicate its potential applications for reducing scar formation and comparative medical purposes.

An isolated bacterium TBE-8, was identified as Leuconostoc mesenteroides according to the sequences of 16S rDNA and the 16S–23S rDNA intergenic spacer region. The probiotic properties of the L. mesenteroides TBE-8 strain were characterized and revealed that TBE-8 could utilize various carbohydrates, exhibited high tolerance to sucrose’s osmotic pressure and acidic conditions, and could mitigate the impact of the bee pathogen Paenibacillus larvae. In addition, we found that the TBE-8 broth increased the expression of the nutrition-related genes major royal jelly protein 1 and vitellogenin in bees by approximately 1400- and 20-fold, respectively. The expression of genes encoding two antibacterial peptides, hymenoptaecin and apidaecin, in the bee abdomen was significantly increased by 17- and 7-fold in bees fed with the TBE-8 fermented broth. Furthermore, we fed four-frame bee colonies with 50% sucrose syrup containing TBE-8 and can detect the presence of approximately 2 × 106 16S rDNA copies of TBE-8 in the guts of all bees in 24 h, and the retention of TBE-8 in the bee gut for at least 5 days. These findings indicate that the L. mesenteroides TBE-8 has high potential as a bee probiotic and could enhance the health of bee colonies.

Background According to recent evidence, psychobiotics exert beneficial effects on central nervous system-related diseases, such as mental disorders. Lactobacillus plantarum PS128 (PS128), a novel psychobiotic strain, improves motor function, depression, and anxiety behaviors. However, the psychobiotic effects and mechanisms of PS128 in Alzheimer’s disease (AD) remain to be explored. Objectives The goal of the current study was to evaluate the beneficial effects of PS128 and to further elucidate its mechanism in AD mice. Methods PS128 (1010 colony-forming unit (CFU)/ml) was administered via oral gavage (o.g.) to 6-month-old male wild-type B6 and 3 × Tg-AD mice (harboring the PS1M146V, APPswe and TauP30IL transgenes) that received an intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg) or vehicle (saline) for 33 days. After serial behavioral tests, fecal short-chain fatty acid levels and AD-related pathology were assessed in these mice. Results Our findings show that intracerebroventricular injection of streptozotocin accelerated cognitive dysfunction associated with increasing levels of glycogen synthase kinase 3 beta (GSK3β) activity, tau protein phosphorylation at the T231 site (pT231), amyloid-β (Aβ) deposition, amyloid-β protein precursor (AβPP), β-site AβPP-cleaving enzyme (BACE1), gliosis, fecal propionic acid (PPA) levels and cognition-related neuronal loss and decreasing postsynaptic density protein 95 (PSD95) levels in 3 × Tg-AD mice. PS128 supplementation effectively prevented the damage induced by intracerebroventricular injection of streptozotocin in 3 × Tg-AD mice. Conclusions Based on the experimental results, intracerebroventricular injection of streptozotocin accelerates the progression of AD in the 3 × Tg-AD mice, primarily by increasing the levels of gliosis, which were mediated by the propionic acid and glycogen synthase kinase 3 beta pathways. PS128 supplementation prevents damage induced by intracerebroventricular injection of streptozotocin by regulating the propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis in 3 × Tg-AD mice. Therefore, we suggest that PS128 supplementation is a potential strategy to prevent and/or delay the progression of AD.

In this review, 170 natural substances, including steroid, diterpenoid, sesquiterpenoid, peptide, prostaglandin, base, chlorolipid, bicyclolactone, amide, piperazine, polyketide, glycerol, benzoic acid, glycyrrhetyl amino acid, hexitol, pentanoic acid, aminoethyl ester, octadecanone, alkaloid, and a 53-kD allergenic component from octocorals belonging to genus Dendronephthya, were listed. Some of these compounds displayed potential bioactivities.

A tetrazolium salt, 2-[2-methoxy-4-nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium (WST-8), has been used widely to determine cell viability, however, its application in the field of reproduction is still limited due to this assay merely providing information regarding cell viability. The aim of this study was to correlate the WST-8 reduction rate with various sperm quality-related parameters (i.e., sperm viability, motility, progressive motility, acrosome integrity and mitochondria integrity) in order to provide a rapid, reliable and affordable assessment for boar semen quality evaluation. Using different ratios of active/damaged sperm cells, we first validated our sample preparations by standard flow cytometry and computer-assisted sperm analysis. Further analyses demonstrated that the most efficient experimental condition for obtaining a reliable prediction model was when sperm concentration reached 300 &times, 106 cells/mL with the semen/cell-counting kit-8 (CCK-8&reg, ) ratio of 200/10 and incubated time of 20 min. Under this set up, the WST-8 reduction rate (differences on optic density reading value, &Delta, OD at 450 nm) and sperm parameters were highly correlated (p &lt, 0.01) for all sperm parameters evaluated. In the case of limited semen samples, a minimal semen concentration at 150 &times, 106 cells/mL with the semen/CCK-8&reg, ratio of 200/20 and incubation time for 30 min could still provide reliable prediction of sperm parameters using the WST-8 assay. Our data provide strong evidence for the first time that the WST-8 assay could be used to evaluate boar semen quality with great potential to be applied to different mammalian species.

Five 8,17-epoxybriaranes, including three new compounds&mdash, briarenols I&ndash, K (1&ndash, 3), along with two known analogues, briaexcavatolide P (4) and briaexcavatin P (5), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1&ndash, 3 were elucidated by spectroscopic methods, including 1D and 2D NMR studies and (+)-HRESIMS. Briarane 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) release from RAW 264.7.

Copper acetate mediated (4 + 2) annulation of sulfonylacetylenes with salicylic acids provides sulfonyl chromen-4-ones in the presence of benzotriazol-1-yloxy tri(dimethylamino)phosphonium hexafluorophosphate (BOP, Castro’s reagent) and 4-dimethylaminopyridine (DMAP) in MeNO2 at reflux for 3 h. The uses of various metal complexes and activating reagents are investigated for facile and efficient transformation. A plausible mechanism is proposed.

A new natural indole, vibrindole B (1), together with known analogs, vibrindole A (2), trisindoline (3), norharmane (4), and 3-(hydroxyacetyl)indole (5), produced by the bacterium Pseudovibrio denitrificans P81, were isolated from a sponge, Aaptos species. The structures of indoles 1 to 5 were established by spectroscopic methods. The proposed biosynthetic pathway of 1 to 5 is also discussed, starting from tryptophan. Moreover, indoles 1 to 3 were found to exhibit cytotoxicity toward T24 tumor cells with IC50 values of 1.71 ± 0.11, 4.53 ± 0.14, and 2.26 ± 0.26 µM, respectively.

Composite photocatalysts comprising graphitic carbon nitride (g-C3N4) and graphene materials were synthesized and evaluated in the photocatalysis of bisphenol A (BPA) with a focus on elucidating the reaction mechanism. Embedding reduced graphene oxide (rGO) to g-C3N4 significantly accelerated the photocatalysis rate of BPA by three folds under visible light irradiation at neutral pH. We showed that rGO synthesized in intimate contact with g-C3N4 increased the surface areas and electrical conductivity of the g-C3N4 composites and promoted the electron-hole pair separation. The BPA photodegradation mechanism involved selective oxidants as superoxide (O2•−) and singlet oxygen (1O2) that were formed through one-electron reduction of O2 and the unique oxidation of O2•− by photogenerated hole (h+), respectively. The synthesized photocatalyst exhibited superior visible light photoreactivity to that of N-doped P25 TiO2, good photo-stability and reuse potential, and was operative in complex wastewater. rGO embedded g-C3N4 achieved good photomineralization of BPA at 80% in 4 h compared to 40% of bare g-C3N4. This study sheds light on the photocatalysis mechanism of BPA with a metal-free, promising rGO/g-C3N4 photocatalyst.

Two novel 16-membered tetraene marcolides, bafilomycins N (1) and O (2), along with two known analogues, JBIR-100 (3) and bafilomycin K (4) were produced from isolate GIC10-1, a Streptomyces sp. strain that was originally cloned from bacterial communities associated with marine sponge Theonella sp. The structures of new bafilomycins 1 and 2 were established by using spectroscopic methods and comparing the spectroscopic data with those of known related metabolites. Compounds 1 and 2 were proven to be the first 14-methylbafilomycins to be isolated. Cytotoxicity of these compounds toward various cancer cell lines also is described.

In this work, we developed a concise synthetic route for the synthesis of polysubstituted naphthalenes starting from commercially available isovanillin and its derivatives. Reaction with styryl bromide via O-styrylation, Claisen rearrangement, ene reaction, and O-alkylation occurred in high yields. The key structures were confirmed by single-crystal X-ray diffraction.

Prodigiosin (PG), a red tripyrrole pigment, belongs to a member of the prodiginine family and is normally secreted by various sources including Serratia marcescens and other Gram-negative bacteria. The studies of PG have received innovative devotion as a result of reported antimicrobial, larvicidal and anti-nematoid immunomodulation and antitumor properties, owing to its antibiotic and cytotoxic activities. This review provides a comprehensive summary of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, the current evidence-based understanding of the biological activities and medicinal potential of PG is employed to determine the efficacy, with some reports of information related to pharmacokinetics, pharmacodynamics and toxicology.

In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A&ndash, D (1&ndash, 4), along with three known compounds, 12&alpha, acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1&ndash, 7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1&ndash, 7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

A facile route to the synthesis of γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 has been developed, achieving moderate to good yields via the (1) NaH mediated Michael addition of β-ketosulfones 3 and methyl acrylate in refluxing THF and (2) NaBH4 mediated stereoselective reduction/lactonization of δ-ketoesters 4 in boiling MeOH, or (3) boron trifluoride etherate mediated ring-opening of lactones 5 in MeOH at reflux.

The aim of this study was to investigate the effect of nonylphenol (NP), a widely used surfactant, on the reproductive performance of male Brown Tsaiya ducks (Anas platyrhynchos) (MBBTDs). Mature MBBTDs (n=100) were treated with NP by daily gavaging of 0, 1 (NP1), 10 (NP10) and 250 (NP250) mg/kg-BW/d for 14 wk. Semen quality, fertilization rate and specific factors in blood plasma were measured. Weights of organs were also measured at 14 wk after NP administration. Ducks from each treatment (n=4) were continually treated with NP thereafter for 12 mo to observe changes of tissue ultrastructure by microscopic examination. The results showed that ducks treated with amounts of NP of greater than 1mg NP/kg BW/d (NP1) for 14 wk had decreased sperm viability (32.3%) compared to those in the control group (74.1%, P0.05). The fertilization rate of ducks treated with 250mg NP/kg-BW/d (NP250) for 14 wk was reduced (21.0%) compared to the control group (74.5%, P0.05). Plasma aminotransferase (AST) and alanine aminotransferase (ALT) activities were also greater in NP250 group at the 14th wk post-treatment. Plasma testosterone concentrations were increased by NP1 treatment at the 14th wk post-treatment. Administration at dosage 250mg NP/kg-BW/d for 12 mo resulted in reduced sperm counts (P0.05) and histopathological changes, such as dilated seminiferous tubules (P0.05) and degenerated spermatocytes (P0.05). These findings strongly suggest that NP adversely affects the reproductive performance of MBBTDs.

Two new eunicellin-type diterpenoids, cladieunicellins R ( 1 ) and S ( 2 ), were isolated from the octocoral Cladiella tuberculosa and their structures were elucidated by spectroscopic methods. Eunicellin 1 was proven to be the first 2,6-hemiketal eunicellin and 2 was found to exhibit moderate cytotoxicity toward the MOLT-4, K562, and SUP-T1 cells.

Tin triflate-promoted one-pot intramolecular annulation of α-geranyl or α-farnesyl β-ketosulfones 3–4 affords the respective bicyclic or tricyclic sulfonyl dihydropyrans 5–6 in moderate to good yields via a cascade cation-olefin-carbonyl carbocyclization process. The starting materials 3 and 4 were obtained by K2CO3-mediated α-geranylation or α-farnesylation of β-ketosulfones 1 with bromides 2a or 2b. The structures of the key products were confirmed by X-ray crystallography.

Eight new briarane diterpenoids, designated briarenolides M–T (1–8), were isolated from an octocoral identified as Briareum sp. The structures of briaranes 1–8 were established by spectroscopic methods and by comparison of the spectroscopic data with those of known analogues. The relationship between 1H and 13C NMR chemical shifts of 2-hydroxybriaranes possessing of (A) a Δ3,5(16)-conjugated diene moiety or (B) a Δ3,5-conjugated diene moiety are described. Briarenolides M (1), P (4), S (7), and T (8) were found to inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein and briarenolides N (2), P (4), and T (8) were found to inhibit the accumulation of the pro-inflammatory cyclooxygenase-2 (COX-2) protein in LPS (lipopolysaccharide)-stimulated RAW264.7 macrophage cells.

The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after infection. The Evans blue method and BBB junctional protein expressions were used to measure changes in the BBB. Hematoxylin and eosin staining was used to analyze pathological changes in the mice brains following 1-3 weeks of infection with A. cantonensis. The levels of 14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different isoform distributions of 14-3-3 proteins and changes in BBB junctional proteins in the mice brain meninges. Dexamethasone was injected intraperitoneally from the seventh day post infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional proteins. The amounts of Evans blue, tight junction and 14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in 14-3-3 protein isoforms β and γ in the CSF in the second and third weeks after infection compared to the controls and first week of infection, which were correlated with the severity of BBB damage in brain histology, and Evans blue extravasation. Using IHC to assess the distribution of 14-3-3 protein isoforms and changes in BBB junctional proteins in the mice brain meninges, the expressions of isoforms β, γ, e, and θ and junctional proteins occludin and claudin-5 in the brain meninges increased over a 3-week period after infection compared to the controls and 1 week after infection. The administration of dexamethasone decreased the expressions of BBB junctional proteins occludin and claudin-5 in the mice brain meninges. Our findings support that 14-3-3 proteins β and γ can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic meningitis caused by A. cantonensis.

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.

A new 16-membered diene macrolide, bafilomycin M ( 1 ), was produced from a Streptomyces sp. GIC10-1, which was originally isolated from a marine sponge Theonella sp. The structure of 1 was established by spectroscopic methods and this compound was found to exhibit cytotoxicity toward K-562, HL-60, SUPT-1, and LNCaP tumor cells with IC 50 values 0.060, 0.011, 0.047, and 0.389 μg/mL, respectively.

The application of appropriate animal models and techniques for the study of osteoporosis is important. Lanyu pigs, a local miniature breed, have been widely used in various biomedical studies in Taiwan. This study aimed to induce bone loss in Lanyu pigs and to examine whether porcine induced pluripotent stem cell (piPSC)-derived osteoblast-like cells could recover bone mass of tibiae via local cell transplantation. piPSCs were directed to differentiate into osteoblast-like cells using osteogenic medium, and differentiated cells expressed osteogenic markers and phenotypes. Twenty mature female Lanyu pigs were divided into four groups, including control (C, 1% calcium diet), treatment 1 (T1, ovariectomy + 1% calcium diet), treatment 2 (T2, ovariectomy + 0.5% calcium diet), and treatment 3 (T3, ovariectomy + 0.5% calcium diet + 1 mg/kg of prednisolone) and were subjected to bone loss induction for twelve months. Micro-CT images revealed that the lowest trabecular bone parameters, such as trabecular bone volume, thickness, separation, number, and total porosity, were detected in the T3 group. The lowest proportions of cortical bone in the proximal metaphysis, proximal diaphysis, and distal diaphysis were also found in the T3 group. These results indicate that ovariectomy, calcium restriction, and prednisolone administration can be applied to induce proper bone loss in Lanyu pigs. After bone loss induction, pigs were subjected to cell transplantation in the left tibiae and were maintained for another six months. Results showed that transplanted piPSC-derived osteoblast-like cells significantly improved trabecular bone structures at transplanted sites and maintained cortical bone structures in the proximal metaphysis. In conclusion, the therapeutic potential of piPSC-derived osteoblast-like cells was confirmed via cell transplantation in the left tibiae of Lanyu pigs. These findings reveal the therapeutic potential of piPSCs for glucocorticoid-induced bone loss in pig models.

In this article, a concise, easy-operational, and high-yield method for the synthesis of 2-aryl-3-sulfonylchromans is described by two-step routes: (i) NH4OAc mediated Knoevenagel condensation of β-ketosulfones and o-hydroxybenzaldehydes in a cosolvent of toluene and THF at reflux for 10 h, and (ii) NaBH4 promoted regio- and stereocontrolled reduction of the resulting 2-arylchromen-2-ols in a cosolvent of MeOH and THF at rt for 1 h. This protocol provides a highly effective (4+2) annulation via one carbon–oxygen and one carbon–carbon bond formations.

Summary Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2,760 air and soil samples screened from 2014-2016, 451 A. fumigatus isolates were recovered from 266 samples, and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole, or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates, respectively. Most (29, 85.3%) azole-resistant isolates harbored TR34/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34/L98H isolates and the occurrence of TR34/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. This article is protected by copyright. All rights reserved.

The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (

Three new 8-hydroxybriaranes&mdash, fragilides R&ndash, T (1&ndash, 3) were obtained from a sea whip gorgonian coral Junceella fragilis. The structures of briaranes 1&ndash, 3 were elucidated by using spectroscopic methods, including 1D (1H and 13C NMR), 2D (COSY, HSQC, HMBC, and NOESY experiments) NMR studies, and (+)-HRESIMS. Fragilides S and T (2 and 3) are the only briaranes known to possess 8&alpha, hydroxy and 17&beta, methyl groups, respectively. Briarane 2 exerted an inhibition effect on iNOS release from RAW264.7, a macrophage cell line that originated from a mouse monocyte macrophage, stimulated with lipopolysaccharides.

Persistent inflammation and oxidative stress play a pathogenic role in the high cardiovascular morbidity and mortality of hemodialysis patients. Heme oxygenase-1 is considered to have anti-inflammatory and antioxidant properties. This study assessed the association between the length of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene microsatellite promoter and cardiovascular events and mortality among hemodialysis patients.Study participants were recruited from October 1, 2006 to December 31, 2006. The allelic frequencies of the length of guanosine thymidine dinucleotide repeats (the S allele represents shorter [27] repeats, and the L allele represents longer [≥ 27] repeats) in the heme oxygenase-1 gene promoter were analyzed in 1080 unrelated chronic hemodialysis patients and 365 healthy controls for distribution comparison. Cardiovascular events and mortality were the study outcomes, and the hemodialysis patients were followed until June 30, 2011.The genotype proportions were 20.6%, 48.8%, and 30.6% for S/S, S/L, and L/L, respectively, in the hemodialysis patients and comparable with those proportions in healthy controls. The patients with the L/L genotype had significantly higher baseline serum high-sensitivity C-reactive protein and malondialdehyde levels than the patients with the S/S or S/L genotypes. During a median follow-up of 50 months, 307 patients died. A Kaplan-Meier survival analysis showed the highest cardiovascular events and all-cause mortality in patients with the L/L genotype. The adjusted hazard ratios (95% confidence intervals) for each L allele in additive model were 1.42 (1.20 to 1.67 [P0.001]) for cardiovascular events and 1.19 (1.01 to 1.40 [P=0.03]) for all-cause mortality.Chronic hemodialysis patients with longer lengths of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter exhibit higher inflammation and oxidative stress. These patients have higher risk of long-term cardiovascular events and mortality.

A novel norcembranoidal diterpene, sinulanorcembranolide A (1), which was found to possess a new carbon skeleton, was isolated from an octocoral identified as Sinularia gaweli. The structure of 1 was elucidated by spectroscopic methods. Sinulanorcembranolide A (1) was proven to be the first norcembranoidal diterpene with carbon–carbon linages between C-5/13 and C-7/12. A plausible biosynthetic pathway of 1 was proposed.

Three new clovane-related sesquiterpenoids, rumphellclovanes C–E (1–3), and a new natural clovane, clovan-2,9-dione (4), were isolated from a gorgonian coral Rumphella antipathies. The structures of clovanes 1–4 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Rumphellclovane C (1) was proven to be the first clovane-type sesquiterpenoid containing an e-lactone moiety. A plausible biosynthetic pathway between clovanes 1 and 2 was proposed. Clovane 4 displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

A new sterol, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methyl-cholest-6,9(11)-dien-3β-ol (1), and two known sterols, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (2) and 24-methylenecholestane-1α,3β,5α, 6β,11α-pentol (3), were isolated from the soft coral Sinularia gaweli. The structure of sterol 1 was established by spectroscopic methods and by comparison of the spectral data with those of known analogues. The cytotoxicity of sterols 1–3 towards various tumor cells is reported.

Accelerating ions from rest in a plasma requires extra considerations because of their heavy mass. Low phase velocity fields or quasi-electrostatic fields are often necessary, either by operating above or near the critical density or by applying other slow wave generating mechanisms. Solid targets have been a favorite and have generated many good results. High density gas targets have also been reported to produce energetic ions. It is interesting to consider acceleration of ions in laser-driven plasma configurations that will potentially allow continuous acceleration in multiple consecutive stages. The plasma will be derived from gaseous targets, producing plasma densities slightly below the critical plasma density (underdense) for the driving laser. Such a plasma is experimentally robust, being repeatable and relatively transparent to externally injected ions from a previous stage. When optimized, multiple stages of this underdense laser plasma acceleration mechanism can progressively accelerate the ion...

Background Spironolactone has been shown to reduce cardiovascular death in patients with mild-to-moderate chronic kidney disease (CKD), but its risks and benefits in advanced CKD remain unsettled. We aimed to assess whether spironolactone reduces cardiovascular mortality and morbidity in pre-dialysis stage 5 CKD patients. Methods Using Taiwan's National Health Insurance Research Database from January 2000 to June 2009, we enrolled 27,213 pre-dialysis stage 5 CKD adult patients, in whom 1363 patients were treated with spironolactone (user) and 25,850 were not (nonuser). Outcomes were all-cause mortality, hospitalization for heart failure (HHF) and major adverse cardiac event (MACE, the composite of acute myocardial infarction and ischemic stroke). Patients were followed up till December 31, 2009. Results Over 85,758 person-years of follow-up, spironolactone users had higher incidence for all-cause mortality (24.7/100 person-years vs. 10.6/100 person-years), infection-related death (4.4/100 person-years vs. 1.7/100 person-years) and HHF (4.0/100 person-years vs. 1.4/100 person-years). Multivariable Cox hazards model showed that spironolactone users were associated with higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.24–1.46), infection-related death (aHR 1.42, CI 1.16–1.73) and HHF (aHR 1.35, CI 1.08–1.67) as compared to nonusers. The risks for cardiovascular mortality, MACE and hyperkalemia-associated hospitalization were similar between two groups. After matching users and nonusers (1:3 ratio) by propensity scores, the results were consistent in matched cohort and across subgroups. Conclusions Spironolactone may be associated with higher risks for all-cause and infection-related mortality and HHF in pre-dialysis stage 5 CKD patients. Spironolactone should be used with caution in advanced CKD patients.

Fe(OTf)3-mediated one-pot (3+3) cycloaddition of β-ketosulfones 1 with prenyl alcohol (2) in MeNO2 affords sulfonyl dihydropyrans 5 in good yields via a sequential intermolecular α-prenylation followed by intramolecular Friedel–Crafts alkylation. The method provides a highly effective condition.

The structures, names, bioactivities and references of 105 natural products obtained from gorgonian corals belonging to the family Plexauridae with an Indo-Pacific distribution are described in this review. All compounds mentioned in this review were obtained from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella.

OBJECTIVE The current study aimed to investigate whether microalbuminuria or moderately decreased glomerular filtration rate (GFR) is a better predictor for the development and progression of retinopathy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Type 2 diabetic patients without cardiovascular diseases, malignancy, pregnancy, and acute intercurrent illness were enrolled between 1 August 2001 and 31 December 2002. All participants provided their detailed medical history and underwent an eye fundus examination. They were followed up in outpatient clinics, and serum creatinine, urinary albumin-to-creatinine ratio (UACR), and retinal photographs were followed up annually until 31 December 2009. The primary outcomes were development and progression of diabetic retinopathy and nephropathy. The secondary outcomes were cardiovascular events and all-cause mortality. RESULTS Among 487 participants, 81 subjects had normoalbuminuria and moderate renal impairment (baseline eGFR 30–59.9 mL/min/1.73 m2), and 106 subjects had microalbuminuria and baseline eGFR ≥60 mL/min/1.73 m2. Patients with microalbuminuria and eGFR ≥60 mL/min/1.73 m2 had a significantly greater risk for development and progression of diabetic retinopathy (HR 3.34 [95% CI 1.04–10.70]) compared with those with moderate renal impairment and normoalbuminuria after multivariate adjustment. Risks for renal outcome, cardiovascular events, and all-cause mortality were not significantly different between the two groups. CONCLUSIONS Microalbuminuria has a greater impact on predicting the development and progression of diabetic retinopathy compared with moderate decline in GFR among type 2 diabetic patients.

Aberrant TGFβ signaling pathway may alter the expression of down-stream targets and promotes ovarian carcinogenesis. However, the mechanism of this impairment is not fully understood. Our previous study has identified RunX1T1 as a putative SMAD4 target in an immortalized ovarian surface epithelial cell line, IOSE. In this study, we report that transcription of RunX1T1 was confirmed to be positively regulated by SMAD4 in IOSE cells and epigenetically silenced in a panel of ovarian cancer cell lines by promoter hypermethylation and histone methylation at H3 lysine 9. SMAD4 depletion increased repressive histone modifications of RunX1T1 promoter without affecting promoter methylation in IOSE cells. Epigenetic treatment can restore RunX1T1 expression by reversing its epigenetic status in MCP3 ovarian cancer cells. When transiently treated with a demethylating agent, the expression of RunX1T1 was partially restored in MCP3 cells, but gradual re-silencing through promoter re-methylation was observed after the treatment. Interestingly, SMAD4 knockdown accelerated this re-silencing process, suggesting that normal TGF-beta signaling is essential for the maintenance of RunX1T1 expression. In vivo analysis confirmed that hypermethylation of RunX1T1 was detected in 35.7% (34/95) of ovarian tumors with high clinical stages (P=0.035) and in 83% (5/6) of primary ovarian cancer-initiating cells. Additionally, concurrent methylation of RunX1T1 and another SMAD4 target, FBXO32 which was previously found to be hypermethylated in ovarian cancer was observed in this same sample cohort (P< 0.05). Restoration of RunX1T1 inhibited cancer cell growth. Taken together, dysregulated TGFβ/SMAD4 signaling may lead to epigenetic silencing of a putative tumor suppressor, RunX1T1, during ovarian carcinogenesis.

A novel 2-ketobriarane diterpenoid, briarenolide E (1), was isolated from an octocoral Briareum sp. The structure of briarane 1 was elucidated by interpretations of spectral data. Compound 1 displayed modestly inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.

Objective To assess the effect of pioglitazone on renal outcome, including urinary albumin excretion and estimated glomerular filtration rate (eGFR), in diabetic patients. Design A prospective, randomized, open-labeled, controlled study. Setting Taipei Veterans General Hospital. Patients Sixty type 2 diabetic patients treated with sulfonylureas and metformin, whose glycated hemoglobin (HbA1c) levels were between 7% and 10% and eGFR was between 45 and 125 mL/min/1.73 m2. Intervention The patients were randomized to receive acarbose or pioglitazone and followed up for 6 months. Thirty patients were randomly assigned to receive acarbose, and 30 patients were assigned to receive pioglitazone. Measurements The primary study endpoint was the changes in the urinary albumin-to-creatinine ratio (UACR). The secondary endpoint was the changes in eGFR and other parameters. Results After 6 months of treatment, the mean changes in UACR were -18 ± 104 and 12 ± 85 (p = 0.25, between groups) for the acarbose and pioglitazone groups, respectively. The mean changes in eGFR were 0 ± 14 and -7 ± 16 mL/min/1.73 m2 (p = 0.09, between groups) for the acarbose and pioglitazone groups, respectively. The reductions in HbA1c were similar in both groups. Fasting blood glucose was lower in the pioglitazone group than in the acarbose group. Significant body weight gain was observed in the pioglitazone group as compared with the acarbose group (1.3 ± 2.8 vs. -0.6 ± 1.5 kg, p = 0.002). Conclusion In type 2 diabetic patients who were treated with sulfonylureas and metformin and possessed HbA1c levels between 7% and 10%, additional acarbose or pioglitazone for 6 months provided similar glycemic control and eGFR and UACR changes. In the pioglitazone group, the patients exhibited significant body weight gain. Trial registration ClinicalTrials.gov NCT01175486.

We present our recent experimental results of monoenergetic protons accelerated from the interaction of an intense terawatt CO2 laser pulse with a near-critical hydrogen gas target, with its density profile tailored by a hydrodynamic shock. A 5-ns Nd:YAG laser pulse is focused onto a piece of stainless steel foil mounted at the front edge of the gas jet nozzle orifice. The ablation launches a spherical shock into the near-critical gas column, which creates a sharp density gradient at the front edge of the target, with ~ 6X local density enhancement up to several times of critical density within ~

A novel ubiquinone derivative, pseudoalteromone A ( 1 ), possessing a 9C nor-monoterpenoid moiety was produced from a marine bacterium Pseudoalteromonas sp. CGH2XX. This bacterium is originally isolated from a cultured-type octocoral Lobophytum crassum . The structure of ubiquinone 1 was established by spectroscopic methods. Pseudoalteromone A ( 1 ) exhibited significant cytotoxicity toward the MOLT-4 (human acute lymphoblastic leukemia, IC 50 = 3.764 μg/mL) cells and displayed a significant inhibitory effect (inhibition rate 45.1%) on the release of elastase by human neutrophils at a concentration of 10 μg/mL.