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One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout–derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12-hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than with GRR beverage. Elimination rates were considerably slower with GRR, allowing for achievement of steady-state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. Cancer Prev Res; 4(3); 384–95. ©2011 AACR.

Supplementary Tables from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China

Supplementary Figure from Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China

A 2-thiobenzothiazole/p-phenylenediamine vulcanization intermediate has been characterized by means of ultra-high-performance liquid chromatography–tandem quadrupole time-of-flight mass spectrometry. Pregenerated 2-thiobenzothiazole/p-phenylenediamine intermediate has a clear effect on accelerating the sulfur crosslinking reaction. Therefore, the generation of vulcanization active species can act as a proof that p-phenylenediamine antioxidant could exert an influence on the vulcanization process via a reaction with the accelerator. Based on an analysis of samples from different curing stages, it is speculated that the intermediate is most likely generated in the vulcanization induction period. This research also provides indirect evidence of the effect of zinc oxide on vulcanization. The intermediate can be detected in both solution and vulcanizate. Its formation is likely to be a zinc ion–mediated reversible mechanism involving a radical course.

While research on policy diffusion has attracted the attention of many scholars, little attention has been given to policy reinvention in diffusion. With the aim to explore the influencing factors and combination paths of policy reinvention in the Municipal Solid Waste Classification Policy (MSWCP), this study constructs a theoretical framework concerning internal factors, intergovernmental relations and external influence, and carries out an empirical analysis on the MSWCP of 31 large and medium-sized cities in China using the Qualitative Comparative Analysis. Based on the empirical results, this study identifies the different combination paths that induced local governments to reinvent policies and clarifies the various roles of financial resources, government attention, policy experience, peer competition, learning, and social demand in achieving policy reinvention, which is expected to provide new theoretical and practical enlightenment for policy reinvention research.

In 2012, the Chinese government put forward the “Innovation-driven Development Strategy”, which has its theory origin as well as its practice and policy origin. At this stage, based on the reality of China’s economic development and the prominent role of “lead innovation” to economic development, China urgently needs to adjust the idea of “Innovation-driven Development” in the past to “Innovation-led Development” and should focus on encouraging and supporting “lead innovation” in order to achieve the purpose of the “steady growth and improve quality”.

Tooth developmental stage evaluation is important in dental and chronological age estimation, and it is important for accurate diagnoses and appropriate treatment in dental practice. It is routinely assessed by clinical observations and radiographic techniques. This study aimed at ascertaining tooth developmental stage judgments made by examiners and Mimics software according to the Nolla method with radiographs. Meanwhile, the true tooth developmental stages would be explored with histological analysis. Twenty freshly slaughtered porcine heads were collected and hemisected, and both the left and right mandibular samples were numbered. The developmental stages of the second and third permanent molars (M2 and M3) were evaluated by examiners and Mimics software analysis. The ratio of the radiopaque calcified area to the dental follicle (RCA/DF) at different stages was calculated. Both non-decalcified and decalcified samples were processed for histologic observation. The results showed significant differences between RCA/DF ratios from different developmental stages. There was a high positive correlation between the examiners' evaluation results and Mimics analysis results. Radiograph judgments and histology observation results were consistent from Stages 2-6. However, radiograph images of Stage 1 samples showed only crypts present, while under a surgical operating microscope, a bell-shaped tooth germ was observed. This was also confirmed by normal and hard tissue histology. In conclusion, radiograph judgments made by either examiners or Mimics software were both reliable. Mimics analysis can be a useful tool in evaluating tooth developmental stages. However, judgments need to be made cautiously in early developmental stages.

Authors thank the Leverhulme Trust, EPSRC and the Sinfonia consortium of the EU for grants as well as the Chinese Scholarship Council for a Studentship (YC), all of which helped to support this work. Genome homology and the presence of a putative biosynthetic gene cluster identified Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 as candidate producers of the antibiotic nucleocidin 1. Indeed when these bacterial strains were cultured in a medium supplemented with fluoride (4 mM) they each produced nucleocidin 1 and the previously identified 4'-fluoro-3'-O-β-glucosylated adenosine 2 and its sulfamylated derivative 3. In both of these cases 4'-fluoroadenosine 9 is also identified as a natural product although it has never been observed during fermentations of Streptomyces calvus, the original source of nucleocidin 1. The identity of 4'-fluoroadenosine 9 was confirmed by a total synthesis as well as by its in vitro enzymatic conversion to metabolite 2 using the glucosyl transferase enzyme, NucGT. Postprint Postprint

In the present study, due to the complex and numerous targets of Sarcandrae Herb (also known as Zhong Jie Feng), network pharmacology was performed to analyze its therapeutic effect on 2 cervical cancer cell lines, which could assist with the development of novel therapies. The results suggested that the natural flavonoid quercetin (Que), the effective antitumor ingredient in SH, which is widely present in a variety of plants, may depend on the target, EGFR. Previous studies have shown that EGFR serves a crucial role in the occurrence and development of cervical cancer, but its downstream molecules and regulatory mechanisms remain unknown. The anti-cervical cancer cell properties of Que, which are present in ubiquitous plants, were examined in vitro to identify the association between Que and its underlying pathway using MTT assays, flow cytometry, western blot analysis and Transwell assays. It was found that Que reduced cervical cancer cell viability, promoted G2/M phase cell cycle arrest and cell apoptosis, as well as inhibited cell migration and invasion. The Tyr1068 phosphorylation site of EGFR and the corresponding ERK target were also examined and the 2 kinases were markedly activated by Que. Furthermore, the EGFR inhibitor, afatinib and the ERK inhibitor, U0126 blocked the increase of EGFR and ERK phosphorylation, and resulted in a notable enhancement of apoptosis and cell cycle arrest. Therefore, to the best of our knowledge, the current results provided the first evidence that EGFR and ERK activation induced by Que could resist Que-induced anticancer activities. On this basis, the present study determined the role of EGFR and the underlying signaling pathways involved in the anti-cervical cancer malignant behavior induced by Que and identified the negative regulatory association.

Authors thank the Engineering and Physical Sciences Research Council (EPSRC) for funding and we are grateful to the EPSRC Mass Spectroscopy Service at the University of Swansea for carrying out some of the accurate mass analysis of prepared compounds. A series of five 12-dodecanolides have been synthesised containing CF2 groups at C5, C6, C7, C8 and in one case a double substitution at C5 & C8, as a strategy to bias the conformational space accessed by these macrocycles, and to assess if the analogues may act as mimetics for 12-decenolide pheromones associated with the Emerald Ash Borer. Accordingly individual syntheses of 5,5-difluoro- 5, 6,6-difluoro- 6, 7,7-difluoro- 7, 8,8-difluoro- 8 and 5,5,8,8-tetrafluoro- 9, 12-decanolides is outlined and X-ray structural data was obtained for three (5, 8 and 9) of these compounds. The structures show clearly that the CF2 groups occupy ‘corner’ locations in the macrocycle consistent with their ability to bias accessible conformations. The fluorine containing 12-dodecanolides all generated an electro-antennogram response in female beetles. Postprint

Funding: This research was funded by JSPS KAKENHI through a Grant-in-Aid for Scientific Research (C), grant number JP18K05262. Photoluminescentliquid crystals (PLLCs) have attracted significant attention owing to their broad applicabilityin thermosensing and PL switching. Extensive efforts have been madeto develop bistolane-based PLLCs containing flexible units at both molecular terminals, and it has been revealed that their PL behavior can switch with the phase transition between the crystallineand LC phases. Although slight modulation of the flexible unit structure dramatically alters the LC and PL behaviors, few studies into modification of the flexible units have been conducted. With the aim of achieving dynamic changes in their physical behaviors, we developed a family of bistolane derivatives containing a simple alkyl or a fluoroalkyl flexible chain, and carried out a detailed systematic evaluationof their physical behaviors. Bistolanes containing a simple alkyl chain showed a nematic LC phase, whereas switching the flexible chain in the bistolane to a fluoroalkyl moiety significantly altered the phase to generate a smectic phase. The fluoroalkyl-containing bistolanes displayed a stronger deep blue PL than their corresponding non-fluorinated counterparts, even in the crystalline phase, which was attributed to the construction of rigid molecular aggregates through intermolecular F···H and F···F interactions to suppress non-radiative deactivation. Publisher PDF

Introduction Amelogenin (AMEL) plays critical roles during enamel and dentin matrix deposition and mineralization. Most studies focused on the expression patterns of AMEL through the bud, cap, and bell stages. The spatial-temporal expression of AMEL protein during different mineralization stages, especially from presence of crypts to crown completed stages, remains unknown. Thus, the distribution pattern of AMEL in tooth crown formation from Nolla Stage 1 to 6 was investigated. Methods Porcine mandibular molar tooth germs from Nolla Stage 1 to 6 were obtained. The dynamic morphologic changes of tooth germs were examined by X-ray and surgical operating microscope. The AMEL protein expression was evaluated immunohistochemically, then analyzed semi-quantitatively, and further visualized via heat map. Results Tooth germs continuously increased in size from Nolla Stage 1 to 6. AMEL expression in the newly formed enamel kept negative, but presented intensively positive in the previously formed enamel from Stage 1 to 3. The adjacent enamel-dentin junction (EDJ) was strongly positive during the whole process. In predentin, AMEL was weakly seen at Stage 1 and then dramatically up-regulated from Stage 2 to Stage 3, then down-regulated but was still apparently seen in the whole process. AMEL expression in dentin was decreased during dentin matrix secretion and mineralization. Conclusions This study identified the dynamic distribution of AMEL during porcine tooth crown formation. Semi-quantitative analysis and heat map emerged as reliable indicators in demonstrating AMEL distribution pattern.

Previous studies on the efficiency of traditional iron and steel enterprises have primarily investigated the efficiency of the production phase and have often overlooked the efficiency of pollution controls included in the overall process of iron and steel enterprises. In this study, we investigated the efficiency of the production chain in China and the efficiency of pollution control. In addition, a two-stage model of production and pollution control was established considering undesirable outputs, and the overall efficiency of the iron and steel enterprises were analyzed. From the results, the efficiency of iron and steel enterprises and the efficiency of pollution control were determined to be generally low. Furthermore, pollution control processes were less efficient than production processes, indicating a strong potential for improvement of the efficiency of iron and steel enterprises. Finally, the impact of environmental regulation on the efficiency of iron and steel enterprises formed an “inverted N-type” relationship.

Genus

With the extensive application of deep learning in the field of human rehabilitation, skeleton based rehabilitation recognition is becoming more and more concerned with large-scale bone data sets. The key factor of this task is the two intra frame representations of the combined co-and the inter-frame. In this paper, an inter frame representation method based on RNN is proposed. Pointtion of each joint is joint-coded they are assembled into semantic both spatial and temporal domains.we introduce a global spatial aggregation which is able to learn superior joint co features over local aggregation.

In the process of flight for in-orbit spacecraft, debris and particles in space will collide with the spacecraft at a high speed. These collision will produce strain, pit or perforation on the surface of the spacecraft cabin, forming damage accumulation. Therefore, it is necessary to monitor the strain and impact position of the spacecraft cabin in real time, which will provide a basis for ensuring the reliability and safety of the spacecraft. In this paper, the achievement of strain and vibration information during the process of impact is designed in two ways: touched style and untouched style. The design of touched style needs to meet the requirements of large capacity/ultra-high speed monitoring. The design of untouched style needs to meet the acquisition of high frequency vibration signal in the impact process.

We thank the Engineering and Physical Sciences Research Council, UK, for a research grant. We report a last-step fluorinase-catalyzed [18F]-fluorination of a cysteine-containing RGD peptide. The peptide was attached through sulfur to a modified and more hydrophilic variant of the recently disclosed Barbas linker which was itself linked to a chloroadenosine moiety via a PEGylated chain. The fluorinase was able to use this construct as a substrate for a transhalogenation reaction to generate [18F]-radiolabeled RGD peptides, which retained high affinity to cancer-cell relevant αvβ3 integrins. Postprint

Herein, a multiwalled carbon nanotubes (MWNT)-based colorimetric probe was designed to discover and monitor the level of apolipoprotein-L1 (ApoL1) in lumbar disc herniation (LDH) patients. ApoL1 could be easily found in human serum of the LDH group, but not obviously expressed in the normal control group (Ctrl), spine spondylolisthesis (SSP) group, spinal fracture (SFR) group, and spine scoliosis (SSC) group. Furthermore, the as-prepared MWNT-based probe was also used to track the recovery of LDH patients who have successful surgery operation. The P value of early diagnosis and recovery monitoring was 0.05 for the proposed method and a conventional enzyme-linked immunosorbent assay (ELISA), respectively, suggesting this detection strategy had significant differences compared with the traditional ELISA. All experimental results showed that ApoL1 might be a potential biomarker for early diagnosis of LDH. This proposed detection strategy has a potential application in discovering new biomarkers of diseases.

The authors are grateful to the EPSRC for supporting this work. The authors acknowledge the EPSRC National Mass Spectrometry Facility (Swansea) and D.O’H. thanks the Royal Society for a Wolfson Research Merit Award. A general route to aryl α,β,β-trifluorocyclopropanes is reported and aryl oxidation gave the corresponding α,β,β-trifluorocyclopropane carboxylic acid. Reactions of the corresponding amides with phenol/thiophenol resulted in HF elimination and then conjugate addition. The partially fluorinated cyclopropane has a similar lipophilicity to –CF3 despite three carbon atoms, and it emerges as a novel motif for drug discovery. Postprint Postprint

We acknowledge support from NSF (CHE-1265679) and NIH (5R01DC014423 subaward) (EB), NIH (5R01 DC014423) (HM), the European Reasearch Council (ERC) and the Engineering Science Research Council (EPSRC) (DO'H), FAPESP and CNPq (RAC), the Chinese Scholarship Council (CSC) for studentship support (MY), National Science Foundation (31070972) (HZ), Science and Technology Commission of Shanghai Municipality (16ZR1418300) (HZ), the Shanghai Eastern Scholar Program (J50201) (HZ). VSB thanks NIH grant 1R01GM106121-01A1 and computational time from NERSC. Understanding olfaction at the molecular level is challenging due to the lack of crystallographic models of odorant receptors (ORs). To better understand the molecular mechanism of OR activation, we focused on chiral (R)-muscone and other musk smelling odorants due to their great importance and widespread use in perfumery and traditional medicine, as well as environmental concerns associated with bioaccumulation of musks with estrogenic/antiestrogenic properties. We experimentally and computationally examined the activation of human receptors OR5AN1 and OR1A1, recently identified as specifically responding to musk compounds. OR5AN1 responds at nanomolar concentrations to musk ketone and robustly to macrocyclic sulfoxides and fluorine-substituted macrocyclic ketones; OR1A1 responds only to nitromusks. Structural models of OR5AN1 and OR1A1 based on quantum mechanics/molecular mechanics (QM/MM) hybrid methods were validated through direct comparisons with activation profiles from site-directed mutagenesis experiments and analysis of binding energies for 35 musk-related odorants. The experimentally found chiral selectivity of OR5AN1 to (R)- over (S)-muscone was also computationally confirmed for muscone and fluorinated (R)-muscone analogs. Structural models show that OR5AN1, highly responsive to nitromusks over macrocyclic musks, stabilizes odorants by hydrogen bonding to Tyr260 of transmembrane a-helix 6 and hydrophobic interactions with surrounding aromatic residues Phe105, Phe194 and, Phe207. The binding of OR1A1 to nitromusks is stabilized by hydrogen bonding to Tyr258 along with hydrophobic interactions with surrounding aromatic residues Tyr251 and Phe206. Hydrophobic/nonpolar and hydrogen bonding interactions contribute, respectively, 77% and 13% to the odorant binding affinities, as shown by an atom-based quantitative structure-activity relationship model. Postprint

Estimation errors or uncertainities in expected return and risk measures create difficulties for portfolio optimization. The literature deals with the uncertainty using stochastic, fuzzy or probability programming. This paper proposes a new approach to treating uncertainty. By assuming that the expected return and risk vary within a bounded interval, this paper uses interval analysis to extend the classical mean-variance portfolio optimization problem to the cases with bounded uncertainty. To solve the interval quadratic programming problem, the paper adopts order relations to transform the uncertain programme into a deterministic programme, and includes the investors’ risk preference into the model. Numerical analysis illustrates the advantage of this new approach against conventional methods.

This study was supported by funding from the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the BBSRC Diet and Health Research Industry Club (BBSRC-DRINC), including BB/H532059/1, BB/H004963/1, BB/I006028/1, BB/I005943/1 and BB/J004545/1. A.C. is a Royal Society Wolfson Research Merit Award Holder. Scope : In vitro and in vivo studies suggest that dietary anthocyanins modulate cardiovascular disease risk; however, given anthocyanins extensive metabolism, it is likely that their degradation products and conjugated metabolites are responsible for this reported bioactivity. Methods and results : Human vascular endothelial cells were stimulated with either oxidized LDL (oxLDL) or cluster of differentiation 40 ligand (CD40L) and cotreated with cyanidin-3-glucoside and 11 of its recently identified metabolites, at 0.1, 1, and 10 μM concentrations. Protein and gene expression of IL-6 and VCAM-1 was quantified by ELISA and RT-qPCR. In oxLDL-stimulated cells the parent anthocyanin had no effect on IL-6 production, whereas numerous anthocyanin metabolites significantly reduced IL-6 protein levels; phase II conjugates of protocatechuic acid produced the greatest effects (>75% reduction, p ≤ 0.05). In CD40L-stimulated cells the anthocyanin and its phase II metabolites reduced IL-6 protein production, where protocatechuic acid-4-sulfate induced the greatest reduction (>96% reduction, p ≤ 0.03). Similarly, the anthocyanin and its metabolites reduced VCAM-1 protein production, with ferulic acid producing the greatest effect (>65% reduction, p ≤ 0.04). Conclusion : These novel data provide evidence to suggest that anthocyanin metabolites are bioactive at physiologically relevant concentrations and have the potential to modulate cardiovascular disease progression by altering the expression of inflammatory mediators. Publisher PDF

Scope The physiological relevance of contemporary cell culture studies is often perplexing, given the use of unmetabolized phytochemicals at supraphysiological concentrations. We investigated the activity of physiologically relevant anthocyanin metabolite signatures, derived from a previous pharmacokinetics study of 500 mg 13C5‐cyanidin‐3‐glucoside in eight healthy participants, on soluble vascular adhesion molecule‐1 (VCAM‐1) and interleukin‐6 (IL‐6) in human endothelial cells. Methods and results Signatures of peak metabolites (previously identified at 1, 6, and 24 h post‐bolus) were reproduced using pure standards and effects were investigated across concentrations ten‐fold lower and higher than observed mean (

Background and Purpose Anthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin-3-glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties. Experimental Approach A 500 mg oral bolus dose of 6,8,10,3′,5′-13C5-C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC-ESI-MS/MS with elimination kinetics established using non-compartmental pharmacokinetic modelling. Key Results Seventeen 13C-labelled compounds were identified in the serum, including 13C5-C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from PGA. The maximal concentrations of the phenolic metabolites (Cmax) ranged from 10 to 2000 nM, between 2 and 30 h (tmax) post-consumption, with half-lives of elimination observed between 0.5 and 96 h. The major phenolic metabolites identified were hippuric acid and ferulic acid, which peaked in the serum at approximately 16 and 8 h respectively. Conclusions and Implications Anthocyanins are metabolized to a structurally diverse range of metabolites that exhibit dynamic kinetic profiles. Understanding the elimination kinetics of these metabolites is key to the design of future studies examining their utility in dietary interventions or as therapeutics for disease risk reduction.

This paper combs the landscapes of China’s technological innovation practice during the 40 years of reform and opening up, and describes it as “Four-Stage Climbing” that is, “Learning–Introducing–Supplying Stage” (LIS Stage), “Introducing–Imitating–Improving Stage” (III Stage), “Integrating–Boosting–Creating Stage” (IBC Stage), and the “Innovating–Iterating–Promoting Stage” (IIP Stage). It also explains the background of each stage and its specific innovation model. Furthermore, the paper emphasizes the main features, basic experiences and main lessons of China’s technological innovation practice during the past 40 years. This paper demonstrates that with the deepening of innovation-driven development, especially in the field of “Innovation Leads Development” which is valued by the country and industry, at this stage, it is urgent to pay closer attention to the following issues: first of all, the possible changes in mechanisms of international innovation competition and cooperation under the background of potential reconstruction for international governance; secondly, the occurrence and realization mechanism of Leading Scientific and Technological Innovation in the era of science and technology, as well as the structural and institutional mechanisms of the national innovation ecosystem, and also the ecological niche in which the future scientific innovation subject and technological innovation subject should be in the national innovation ecosystem; furthermore, the mechanism of innovation and development for “science-based industries”; last but not the least, the logical construction of innovation and development research under the Chinese context.

Acute renal failure (ARF) has high mortality and no effective treatment. Nitric oxide (NO) delivery represents a credible means of preventing the damaging effects of vasoconstriction, central to ARF, but design of drugs with the necessary renoselectivity is challenging. Here, we developed N-hydroxyguanidine NO donor drugs that were protected against spontaneous NO release by linkage to glutamyl adducts that could be cleaved by γ-glutamyl transpeptidase (γ-GT), found predominantly in renal tissue. Parent NO donor drug activity was optimized in advance of glutamyl adduct prodrug design. A lead compound that was a suitable substrate for γ-GT-mediated deprotection was identified. Metabolism of this prodrug to the active parent compound was confirmed in rat kidney homogenates, and the prodrug was shown to be an active vasodilator in rat isolated perfused kidneys (EC50 ~50 μM). The data confirm that glutamate protection of N-hydroxyguanidines is an approach that might hold promise in ARF.

BACKGROUND: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. OBJECTIVE: We investigated the ADME of a (13)C5-labeled anthocyanin in humans. DESIGN: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3',5'-(13)C5-C3G). Biological samples were collected over 48 h, and (13)C and (13)C-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: The mean +/- SE percentage of (13)C recovered in urine, breath, and feces was 43.9 +/- 25.9% (range: 15.1-99.3% across participants). The relative bioavailability was 12.38 +/- 1.38% (5.37 +/- 0.67% excreted in urine and 6.91 +/- 1.59% in breath). Maximum rates of (13)C elimination were achieved 30 min after ingestion (32.53 +/- 14.24 mug(13)C/h), whereas (13)C-labeled metabolites peaked (maximum serum concentration: 5.97 +/- 2.14 mumol/L) at 10.25 +/- 4.14 h. The half-life for (13)C-labeled metabolites ranged between 12.44 +/- 4.22 and 51.62 +/- 22.55 h. (13)C elimination was greatest between 0 and 1 h for urine (90.30 +/- 15.28 mug/h), at 6 h for breath (132.87 +/- 32.23 mug/h), and between 6 and 24 h for feces (557.28 +/- 247.88 mug/h), whereas the highest concentrations of (13)C-labeled metabolites were identified in urine (10.77 +/- 4.52 mumol/L) and fecal samples (43.16 +/- 18.00 mumol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. CONCLUSION: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation for

This paper used data from 50 enterprises in China’s iron and steel industry to evaluate their energy efficiency and productivity change. The study first used a conventional data envelopment analysis model and the Malmquist Productivity Index (MPI) to measure the energy efficiency and productivity change over the period 2001–2008. The results indicated inefficiency in many of the plants: The average energy efficiency was only 61.1%. The annual growth rate of productivity was 7.96% over this period and technical change was the main contributor to this growth. The research then took undesirable outputs into consideration by using the Malmquist–Luenberger Productivity Index (MLPI) to explore the productivity change from 2006 to 2008. Omitting undesirable outputs would result in biased efficiency change and technical change. This paper also claimed that environmental regulation has a potentially positive impact on technical change.

This study was supported by funding from the UK Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club (BBSRC-DRINC) (BB/I006028/1). Background: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. Objective: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Method: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM–100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Results: Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (−17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2–36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2–54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no activity toward sVCAM-1, suggesting no additive activity at 1 μM. Conclusions: The present findings suggest that metabolism of flavonoids increases their vascular efficacy, resulting in a diversity of structures of varying bioactivity in human endothelial cells. Publisher PDF

Epidemiological studies indicate that flavonoid intake is inversely associated with the risk of coronary heart disease, yet the mechanisms responsible for their bioactivity are still a matter of debate. Based on the rapid and extensive metabolism of most flavonoids, their health effects most likely result from the biological activity of their metabolites. However, a lack of commercially available compounds/standards has prevented the study of metabolite bioactivity and resulted in a focus on non-physiologically relevant precursor/parent structures. This paper details the synthesis of a series of phenolic glucuronide 1a–e and sulfate 2a–e derivates as candidate metabolites for use as reference compounds in metabolic profiling studies and for the exploration of flavonoid bioactivity.

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout–derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12-hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than with GRR beverage. Elimination rates were considerably slower with GRR, allowing for achievement of steady-state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. Cancer Prev Res; 4(3); 384–95. ©2011 AACR.

Seismic imaging together with global positioning system (GPS) and crustal stress data analyses show that the Mw7.9 2008 Wenchuan earthquake occurred within a distinct area of high crustal stress (∼ 17.5 MPa) and high Poisson's ratio (7–10%) anomalies centered on the Longmen-Shan (Shan means Mountain in Chinese) tectonic fault belt. Low P-wave and S-wave velocities in the southwest (SW) segment contrast with high-velocity anomalies in the central portion (CP) and northeast (NE) segment within the uppermost ∼ 15 km depths along the tectonic fault belt, though a presumably ductile zone with low-velocity anomalies separates the CP and NE segment. The rupture initiated near the southwestern end of the CP at a zone of high Poisson's ratio (σ) which extends down into the lower crust. These low-velocity and high-σ anomalies immediately below the source hypocenter, together with the high crustal stress, indicate the presence of high-pressure fluids from the lower crust, which might have reduced the mechanical strength of the fractured rock matrix and triggered the earthquake. Our study suggests that the structural heterogeneity and high crustal stress played an important role in the nucleation of the Wenchuan earthquake and its rupture process.

Science empowers as a nation’s toughest weapon in the future global competition and cooperation. A large number of countries listed in-house R&D for science-based innovations as their core development strategy in the next decade. This paper conducts multi-case analysis on four science-based innovations in China as a reference for how a new science-based venture superseded in global market and developed indigenous capability to generate much business value as well as scientific value. The four cases detailed are container inspection system, hot redundant JX-100 DCS, high-performance Dawning supercomputers and Chinese-character laser phototypesetting system. We concluded that the successful commercialization of a nationwide and grand scientific project requires the following: (1) visionary scientists’ solid authority, direct participation, business acumen and a strong sense of patriotism, without intermediaries, are the core for successful science-based innovation and commercialization during knowledge transformation; and (2) the powerful and direct support from the policymakers. Forms of support may vary from financial incentives, policy enforcement and endorsement. The consequences for the success of science-based innovations are the creation of highly-skilled manpower, new market as well as shifting away from low-cost strategy to innovative strategy.

2,4-Bis(phenyl)-1,3-diselenadiphosphetane-2,4-diselenide (Woollins’ reagent, WR) reacts with cyanamides (1a–h) in refluxing toluene to afford a series of novel selenazadiphospholaminediselenides (RR′NC N(PhP(Se)SeP(Se)Ph, R=C6H5(CH2)1–3, 4-n-C10H21C6H4 and 4-BrC6H4CH2; R′=H, CH3, C2H5 and C(O)OC2H5 2a–g). Post-treatment of the reaction mixture with water led to the formation of carbamidoyl(phenyl)phosphinodiselenoic acids (RR′NC(NH2)P(SeH)2Ph, R=C6H5(CH2)2–3, 4-n-C10H21C6H4 and 4-BrC6H4CH2; R′=H and CH3, 3b, 3c, 3e and 3f) and selenoureas (RR′NC(Se)NH2, R=C6H5(CH)1–2; R′=CH3 and OC(O)C2H5, 4f and 4h) in moderate to excellent yields. All new compounds are characterised spectroscopically and five X-ray crystal structures are reported.

An isotopically labelled building block, 2,3,4,6-tetra- O -acetyl-1-thio-β- d -[ 13 C 6 ]glucopyranose ( 4 ), is obtained from the commercially available [ 13 C 6 ]- d -glucose. This hexa- 13 C -labelled thioglucose can be employed to make any glucosinolate ( 8 ) for use as an internal standard for isotopic dilution LCMS analysis. Herein three typical glucosinolates in their hexa- 13 C -labelled form: [ glucose - 13 C 6 ]gluconasturtiin, [ glucose - 13 C 6 ]sinigrin and [ glucose - 13 C 6 ]glucoerucin are synthesised by coupling the isotopically labelled thioglucose ( 4 ) with the corresponding hydroximoyl chlorides followed by sulfation with pyridine sulfur trioxide and deacetylation with a catalytic amount of potassium methoxide, respectively.