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All-solid-state Z-scheme photocatalysts for overall water splitting to evolve H2 is a promising strategy for efficient conversion of solar energy. However, most of these strategies require redox mediators. Herein, a direct Z-scheme photoelectrocatalytic electrode based on a WO3-x nanowire-bridged TiO2 nanorod array heterojunction is constructed for overall water splitting, producing H2. The as-prepared WO3-x/TiO2 nanorod array heterojunction shows photoelectrochemical (PEC) overall water splitting activity evolving both H2 and O2 under UV–vis light irradiation. An optimum PEC activity was achieved over a 1.67-WO3-x/TiO2 photoelectrode yielding maximum H2 and O2 evolution rates roughly 11 times higher than that of pure TiO2 nanorods without any sacrificial agent or redox mediator. The role of oxygen vacancy in WO3-x in affecting the H2 production rate was also comprehensively studied. The superior PEC activity of the WO3-x/TiO2 electrode for overall water splitting can be ascribed to an efficient Z-scheme charge transfer pathway between the WO3-x nanowires and TiO2 nanorods, the presence of oxygen vacancies in WO3-x, and a bias potential applied on the photoelectrode, resulting in effective spatial charge separation. This study provides a novel strategy for developing highly efficient PECs for overall water splitting.

In this study, we discuss institutional quality and export product quality within a unified framework and explore the influence of institutional quality on product export quality empirically by mat...

Here, we investigate the intrinsic nonradiative recombination mechanism in hematite single crystals that decides the photocarrier lifetime under solar illumination. On the basis of the small polaron theory, we propose that the photogenerated electron-hole pair along with its induced lattice deformation in hematite could be treated as a pseudocoordination-complex (PCC) dispersed in a solid medium. We demonstrate that the nonradiative recombination rate at different temperatures determined from the transient absorption spectroscopy can be excellently described by the nonradiative transition theory developed previously for parallels of the PCC model. Our finding suggests that at room temperature the nonradiative recombination in hematite substantially depends on the probability of quantum tunneling of the nuclear configuration.

Knowledge of the location, area and extent of rubber plantations is a prerequisite for assessing their ecological and environmental impacts. Mainland Southeast Asia (MSEA) and Yunnan province (MSEA&YN) in China are globally important rubber-planting regions. Rubber cultivation in areas at moderate and low altitudes (6 ha, accounting for 3.32% of the study area. Spatial analyses showed three typical features of the distribution: new plantations at higher (over 1000 m) and lower (below 200 m) elevations, more cultivation in the borderlands (over a half within 60 km buffers), and their northward movement (as far as 25°N). The results of this study have important implications for phenological methods verification in the tropics, and provide valuable information on mature rubber plantations in MSEA&YN.

The Auger recombination in bulk semiconductors can quickly depopulate the charge carriers in a nonradiative way, which, fortunately, only has a detrimental impact on optoelectronic device performance under the condition of high carrier density because the restriction arising from concurrent momentum and energy conservation limits the Auger rate. Here, we surprisingly observed enhanced Auger recombination in an α-Fe2O3 single crystal, a wide bandgap semiconductor with low carrier mobility. The Auger process was ascribed to the Coulombically coupled self-trapped excitons (STEs), and the relaxation of momentum conservation due to the strong spatial localization of these STEs should account for the enhancement. The STE-density dependent kinetics suggested that the strong polaronic effect could cause a micro-heterogeneous distribution of STEs in a high-quality bulk single crystal, which also gave rise to the micro-heterogeneous annihilation dynamics, and a stochastic recombination model was developed and successfully described the STE annihilation dynamics.

Hematite (Fe2O3) is a well-known oxide semiconductor suitable for photoelectrochemical (PEC) water splitting and industry gas sensing. It is widely known that Sn doping of Fe2O3 can enhance the device performance, yet the underlying mechanism remains elusive. In this work, we determine the relationship between electronic structure, optical properties, and PEC activity of Sn-doped Fe2O3 by studying highly crystalline, well-controlled thin films prepared by pulsed laser deposition (PLD). We show that Sn doping substantially increases the n-type conductivity of Fe2O3, and the conduction mechanism is better described by a small-polaron hopping (SPH) model. Only 0.2% Sn doping significantly reduces the activation energy barrier for SPH conduction from at least 0.5 eV for undoped Fe2O3 to 0.14 eV for doped ones. A combination of X-ray photoemission, X-ray absorption spectroscopy, and DFT calculations reveals that the Fermi level gradually shifts toward the conduction band minimum with Sn doping. A localized Fe2+-like gap state is observed at the top of the valence band, accounting for the SPH conduction. Interestingly, different from the literature, only 0.2% Sn doping in Fe2O3 significantly improves the PEC activity, while more Sn decreases it. The improved PEC activity is partially attributed to an increased band bending potential which facilitates the charge separation at the space charge region. The reduced activation energy barrier for SPH will facilitate the transport of photoexcited carriers for the enhanced PEC, which is of interest for further carrier dynamics study.

This paper explores the influence and mechanism of urban rail transit on haze pollution in mainland China. Based on the satellite remote sensing dataset released by the Earth Observing System of Data and Information System (EOSDIS) of the National Aeronautics and Space Administration (NASA) and urban rail transit network data of Robert Schwan, the prefecture-year urban rail transit and haze concentration-related dataset from 2001 to 2018 is collected. Considering the significant spatial autocorrelation of urban haze pollution, a spatial difference-in-differences (SDID) approach is applied to empirically investigate the influence of urban rail transit on haze pollution. The results show that the connection of urban rail transit significantly reduces the urban PM2.5 concentration, and the effect has significant regional heterogeneity. Furthermore, it is found that the substitution effect on motor vehicles is the mechanism in which urban rail transit impacts haze pollution. Based on our findings, accelerating urban rail transit network support, appropriately relaxing the subway application in some large cities, and taking comprehensive measures to attract more residents to choose subway travel is proposed.

Information on where rubber plantations are located and when they were established is essential for understanding changes in the regional carbon cycle, biodiversity, hydrology and ecosystem service...

Regional density is a useful tool for analyzing regional spatial structure as well as a good starting point for analyzing regional CO2 emissions per capita. This paper empirically analyzes the relationship between regional density and per capita CO

Self-trapping of photocarriers due to the strong carrier-phonon interaction is ubiquitous in metal oxides, which exerts detrimental influence on the performance of the oxide-based optoelectronic devices. The self-trapped species could be isolated self-trapped charges (i.e., isolated polarons) or bound self-trapped electron-hole pairs (i.e., polaron-pairs, self-trapped excitons), and they may show distinct dynamic behaviors. Here, we find that the self-trapping in hematite ($\ensuremath{\alpha}\text{\ensuremath{-}}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$) primarily results in self-trapped excitons rather than spatially separated polaronic charges or electron-hole polaron-pairs based on both dynamic and spectral evidence. The formation and recombination of self-trapped excitons are found to be substantially independent of defect concentration varying from monocrystalline to polycrystalline $\ensuremath{\alpha}\text{\ensuremath{-}}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ films. The spectral feature attributed to small electron polarons can only be resolved above the noise floor by raising excitation intensity so that the Auger process dominates the recombination. Based on the comparison of monocrystalline and polycrystalline sample data, we suggest that the isolated electron polaron formation is likely facilitated by defects. Our finding invokes reconsideration of the photocurrent generation mechanism in $\ensuremath{\alpha}\text{\ensuremath{-}}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ photoanodes.

Soil temperature changes in cold regions can have great impacts on the land surface energy and water balance, and hence changes in weather and climate, surface and subsurface hydrology and ecosystem. We investigate the spatiotemporal variations of annual soil temperature at depths of 0, 5, 10, 15, 20, and 40 cm during 1983–2013 using observations at 85 stations on the Tibetan Plateau (TP). Our results show that the climatological soil temperatures exhibit a similar spatial pattern among different depths and they are generally higher than surface air temperature at the individual stations. Spatially averaged soil temperature show that the TP has experienced significant warming trends at all six depths during 1983–2013, and the soil at 0-cm depth has the fastest warming rate among all the six layers and the surface air temperature. The first leading mode of joint empirical orthogonal function (EOF) analysis exhibits a spatially prevailing warming pattern across the six depths. This plateau-wide soil warming correlates very well with surface air temperature and sea surface temperature in response to increasing radiative forcing caused by greenhouse gases. The joint EOF2 displays a southeastern-northwestern dipole pattern on the TP in the interannual-decadal variability of soil temperature at all layers, which appears to be related to the warm season precipitation and anomalous atmospheric circulations. The spatial difference of soil warming rates across stations on the TP is associated primarily with the spatial distribution of precipitation (mainly rainfall), with vegetation, snowfall and elevation playing a rather limited role.

Northeast China (NEC) is an important region for maize (Zea mays L.) production in China, and is the country’s most significant commercial food base. However, NEC is also one of the areas that are most significantly affected by climate change in this country. Maize is sensitive to climatic changes, and to develop effective strategies for guaranteeing regional food security, it is essential to understand the mechanisms of the impacts of climate change and the effectiveness of adaptation measures in NEC. In this study, the Crop-Environment Resource Synthesis (CERES)-Maize v4.5 model, coupled with newly released data for Representative Concentration Pathway (RCP) scenarios, RCP4.5 and RCP8.5, was applied to simulate maize yields for future periods (2020s, 2050s, and 2080s) and to estimate the effect of CO₂ fertilization and the effectiveness of three typical adaptation measures for maize production in NEC. The results indicated a trend of a continuing decline in maize yield for both RCP scenarios, and the decrease in maize yield under RCP8.5 was predicted to be greater than that under RCP4.5. The effect of CO₂ fertilization was forecast to be too small to offset the negative impacts of climate change. Three adaptation measures—changing planting dates, switching to later-maturing cultivars, and breeding new cultivars with high thermal time requirements—could mitigate negative climate change impacts to varying degrees; switching cultivars may exert the most significant effect on increasing maize yields.

We aimed to elucidate the potential mechanisms of long non-coding RNAs (lncRNAs) in the progression of non-small cell lung cancer (NSCLC). The microarray datasets of GSE37764, including 3 primary NSCLC tumors and 3 matched normal tissues isolated from 6 Korean female never-smokers, were downloaded from Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNA in NSCLC samples were identified using NOISeq package. Co-expression network of differentially expressed lncRNAs and mRNA was established. Gene Ontology (GO) and pathway enrichment analysis were respectively performed. Finally, lncRNAs related to NSCLC were predicted by blasting the differentially expressed lncRNAs with all predicted lncRNAs related to NSCLC. A total of 182 and 539 differentially expressed lncRNAs and mRNA (109 up- and 73 down-regulated lncRNAs; 307 up- and 232 down-regulated mRNA) were respectively identified. Among them, 4 up-regulated lncRNAs, like lnc-geranylgeranyl diphosphate synthase 1 (GGPS1), lnc-zinc finger protein 793 (ZNF793) and lnc-serine/threonine kinase 4 (STK4), and 4 down-regulated lncRNAs including lnc-LOC284440 and lnc-peptidylprolyl isomerase E-like pseudogene (PPIEL), and lnc-zinc finger protein 461 (ZNF461) were predicted related to NSCLC. lncSSPS1, lnc-ZNF793 and lnc-STK4 were co-expressed with linker for activation of T cells (LAT) and Lck interacting transmembrane adaptor 1 (LIME1). Lnc-LOC284440, lnc-PPIEL and lnc-ZNF461 were co-expressed with Src-like-adaptor 2 (SLA2) and defensin beta 4A (DEFB4A). Our study indicates that immune response may be a crucial mechanism involved in NSCLC progression. Lnc-GGPS1, lnc-ZNF793, lnc-STK4, lnc-LOC284440, lnc-PPIEL, and lnc-ZNF461 may be involved in immune response for promoting NSCLC progression via co-expressing with LAT, LIME1, SLA2 and DEFB4A.

Background and objectiveDietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health.MethodsIn this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library.ResultsThe AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts.ConclusionIn summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes.

Rice (Oryza) is a staple food in China, and rice yield is inherently sensitive to climate change. It is of great regional and global importance to understand how and to what degree climate change will impact rice yields and to determine the adaptation options effectiveness for mitigating possible adverse impacts or for taking advantage of beneficial changes. The objectives of this study are to assess the climate change impact, the carbon dioxide (CO2) fertilization effect, and the adaptation strategy effectiveness on rice yields during future periods (2011–2099) under the newly released Representative Concentration Pathway (RCP) 4.5 scenario in the Sichuan Basin, one of the most important rice production areas of China. For this purpose, the Crop Estimation through Resource and Environment Synthesis (CERES)-Rice model was applied to conduct simulation, based on high-quality meteorological, soil and agricultural experimental data. The modeling results indicated a continuing rice reduction in the future periods. Compared to that without incorporating of increased CO2 concentration, a CO2 fertilization effect could mitigate but still not totally offset the negative climate change impacts on rice yields. Three adaptive measures, including advancing planting dates, switching to current high temperature tolerant varieties, and breeding new varieties, could effectively offset the negative climate change impacts with various degrees. Our results will not only contribute to inform regional future agricultural adaptation decisions in the Sichuan Basin but also gain insight into the mechanism of regional rice yield response to global climate change and the effectiveness of widely practiced global thereby assisting with appropriate adaptive strategies.

The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40–70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of β-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (−3.97 ± 10.09 µmol/L; −1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population.

Table S1. Summary of 127 hereditary deafness-related genes by target region capture sequencing. (DOCX 16Â kb) (DOCX 15 kb)

Table S2. Overview of target region capture sequencing results of the proband affected by ARNSHL. (DOCX 15Â kb) (DOCX 14 kb)

Accumulating evidence has demonstrated that aberrant miRNAs were involved in carcinogenesis and tumor progression by regulating oncogenes or tumor suppressor expression. Dysregulation of miR-381 has been reported in different tumors. However, the clinical roles and underlying mechanism in non-small cell lung cancer (NSCLC) remains to be elucidated. We found the expression of miR-381 was significantly downregulated in both NSCLC tissues and cell lines. Clinical analysis revealed the reduced miR-381 was obviously associated with advanced TNM stage and lymph node metastasis. Moreover, we disclosed that miR-381 was a novel independent prognostic marker for predicting 5-year survival of NSCLC patients. The ectopic overexpression of miR-381 inhibited cell migration and invasion in vitro and in vivo. Notably, miR-381 could modulate LRH-1 by directly binding to its 3'-UTR. In clinical samples of NSCLC, miR-381 inversely correlated with LRH-1 expression, which performed positive roles in NSCLC migration and invasion. Alteration of LRH-1 expression at least partially abolished the migration and invasion of miR-381 on NSCLC cells. Here, we identified LRH-1 as a functional target of miR-381 in NSCLC. In conclusion, our data indicated that miR-381 inhibited migration and invasion of NSCLC by targeting LRH-1, and may represent a novel potential therapeutic target and prognostic marker for NSCLC.

BACKGROUNDClimate change would cause negative impacts on future agricultural production and food security. Adaptive measures should be taken to mitigate the adverse effects. The objectives of this study were to simulate the potential effects of climate change on maize yields in Heilongjiang Province and to evaluate two selected typical household-level autonomous adaptive measures (cultivar changes and planting time adjustments) for mitigating the risks of climate change based on the CERES-Maize model. RESULTSThe results showed that flowering duration and maturity duration of maize would be shortened in the future climate and thus maize yield would reduce by 11-46% during 2011-2099 relative to 1981-2010. Increased CO2 concentration would not benefit maize production significantly. However, substituting local cultivars with later-maturing ones and delaying the planting date could increase yields as the climate changes. CONCLUSIONThe results provide insight regarding the likely impacts of climate change on maize yields and the efficacy of selected adaptive measures by presenting evidence-based implications and mitigation strategies for the potential negative impacts of future climate change. (c) 2014 Society of Chemical Industry

Lung cancer including non-small cell lung cancer (NSCLC) and small cell lung cancer is one of the most aggressive tumors with high incidence and low survival rate. The typical NSCLC patients account for 80-85 % of the total lung cancer patients. To systemically explore the molecular mechanisms of NSCLC, we performed a molecular network analysis between human and mouse to identify key genes (pathways) involved in the occurrence of NSCLC. We automatically extracted the human-to-mouse orthologous interactions using the GeneWays system by natural language processing and further constructed molecular (gene and its products) networks by mapping the human-to-mouse interactions to NSCLC-related mammalian phenotypes, followed by module analysis using ClusterONE of Cytoscape and pathway enrichment analysis using the database for annotation, visualization and integrated discovery (DAVID) successively. A total of 70 genes were proven to be related to the mammalian phenotypes of NSCLC, and seven genes (ATAD5, BECN1, CDKN2A, FNTB, E2F1, KRAS and PTEN) were found to have a bearing on more than one mammalian phenotype (MP) each. Four network clusters centered by four genes thyroglobulin (TG), neurofibromatosis type-1 (NF1 ), neurofibromatosis type 2 (NF2 ) and E2F transcription factor 1 (E2F1) were generated. Genes in the four network modules were enriched in eight KEGG pathways (p value < 0.05), including pathways in cancer, small cell lung cancer, cell cycle and p53 signaling pathway. Genes p53 and E2F1 may play important roles in NSCLC occurrence, and thus can be considered as therapeutic targets for NSCLC.

VSV-G-pseudotyped lentiviral vectors expressing p16INK4a or p14ARF were used to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell lines lacking endogenous transcripts. Restoration of p16INK4a accumulated cells in the G0/G1 phase of cell cycle and restoration of p14ARF induced their apoptosis, followed by significant growth inhibition. Transduction of primary blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph-positive acute lymphoblastic leukemia (ALL) with p16INK4a or p14ARF virus also resulted in cell growth inhibition and/or apoptosis with a patient-to-patient variation, whereas clonal growth and differentiation of cord blood progenitor cells were not affected by enforced expression of INK4a/ARF. Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in an additive but not synergistic manner. These results suggest that INK4a/ARF protein-mimetic agents may be promising options for Ph-positive leukemias in combination with imatinib mesylate.

Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef. Ser5 produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that Ser5-001 transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR. When Ser5-001 and its two isoforms Ser5-005 and Ser5-008a were expressed from the same mammalian expression vector, only Ser5-001 was stably expressed, whereas the others were poorly expressed due to rapid degradation. In addition, unlike the other isoforms, which are located mainly in the cytoplasm, Ser5-001 is localized primarily to the plasma membrane. To map the critical determinant, Ser5 mutants bearing C-terminal deletions were created. It was found that the 10th transmembrane domain is required for Ser5 stable expression and plasma membrane localization. As expected, only Ser5-001 strongly inhibits HIV-1 infectivity, whereas the other Ser5 isoforms and mutants that do not have the 10th transmembrane domain show very poor activity. It was also observed that the Nef counteractive activity could be easily saturated by Ser5 overexpression. Thus, we conclude that Ser5-001 is the predominant antiviral isoform that restricts HIV-1, and the 10th transmembrane domain plays a critical role in this process by regulating its protein stability and plasma membrane targeting. IMPORTANCE Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express a small protein, Nef, to enhance viral pathogenesis in vivo . Nef has an important in vitro function, which is to make virus particles more infectious, but the mechanism has been unclear. Recently, Nef was reported to counteract a novel anti-HIV host protein, SERINC5 (Ser5). Ser5 has five alternatively spliced isoforms, Ser5-001, -004, -005, -008a, and -008b, and only Ser5-001 has an extra C-terminal transmembrane domain. We now show that the Ser5-001 transcripts are produced at least 10-fold more than the others, and only Ser5-001 produces stable proteins that are targeted to the plasma membrane. Importantly, only Ser5-001 shows strong anti-HIV-1 activity. We further demonstrate that the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization. These results suggest that plasma membrane localization is required for Ser5 antiviral activity, and Ser5-001 is the predominant isoform that contributes to the activity.

e18864Background: The aim of this study was to explore the current practice of Chinese doctors with different clinical specialties regarding fertility preservation (FP) of cancer patients and to de...

Histiocytic necrotizing lymphadenitis (HNL) is a unique form of self-limiting lymphadenitis with an unknown cause. The majority of cases resolve within several months and the disease has a low recurrence rate of 3-4%. In the present study, a prolonged recurrent case of HNL was reported. A 44-year-old female developed recurrent HNL with generalized lymphadenopathy 14 years after the original episode.

Folate is a structurally diverse family of molecules that occur in low concentrations in biological tissues and fluids and therefore present complex challenges to the analytical chemist. As a result, techniques that quantify folates in biological specimens have emerged as a high scientific priority. In this manuscript, isotopic methods using traditional mass spectrometry for the measurement of whole blood total folate and 14 C-accelerator mass spectrometry (AMS) for human kinetic studies are presented. Additionally, recent developments with the intrinsic labeling of spinach folate from a [ 14 C]- para -aminobenzoic is discussed.

Biochemical markers of bone turnover suffer from large analytical and natural fluctuations (20-30%), making small differences in bone resorption impossible to resolve. This limits the clinical utility of such markers for individuals with the skeletal complications associated with many disease states (e.g., metastatic cancer, renal failure, osteoporosis). We are developing the capability to measure small changes (5-10%) in bone turnover rate in vivo by tagging the living skeleton with 41Ca. Among the stable and radioactive calcium isotopes, only 41Ca is useful for direct quantitation of bone turnover because it is extremely rare in nature and radiologically benign (105 years half-life, pure electron capture decay). The ratio of this tracer to total calcium remains quantifiable in body fluids and excreta via accelerator mass spectrometry (AMS) for many years following a single physiological-sized oral or intravenous dose. The highly automated AMS instrumentation and streamlined sample preparation allows a single operator to prepare or run more than 100 samples per day—significantly more than other 41Ca programs worldwide. We intend to exploit these measurements for earlier diagnosis of pathological processes and interactive intervention with therapeutic agents, allowing modulation of these agents to obtain the best individual result for a patient.

The ability of beta-carotene to deliver bioactive retinoids to tissues is highly variable. A clearer understanding of the environmental and genetic factors that modulate the vitamin A potential of beta-carotene is needed.Assess the vitamin A value of orally administered beta-carotene relative to a co-administered reference dose of preformed vitamin A.Equimolar doses (30 micromol) of hexadeuterated D6 beta-carotene and D6 retinyl acetate were orally co-administered in an emulsified formulation to a male subject. The plasma concentration time courses of D6 retinol (derived from D6 retinyl acetate) and bioderived D3 retinol (from D(6) beta-carotene) were determined for 554 h postdosing using gas chromatography/mass spectrometry. Intact D6 beta-carotene plasma concentrations were determined by high-pressure liquid chromatography. The ratio of the two forms of vitamin A, D6 retinol/D3 retinol, at any single time point is postulated to reflect the quantity of vitamin A derived from beta-carotene relative to preformed vitamin A. Additionally, a minute amount of 14C beta-carotene (50 nCi; 0.27 microg) was included in the oral dose and cumulative 24-h stool and urine samples were collected for two weeks to follow absorption and excretion of the b-carotene. The 14C nuclide was detected using accelerator mass spectrometry (AMS). Results During the absorption/distribution phase (3-11 h) the D6/D3 ratio of the two retinols was not stable and ranged between a value of 3 and 16. Between 11 and 98 h postdosing the ratio was relatively stable with a mean value of 8.5 (95 % CI: 7.5, 8.7). These data suggest that in this subject and under these conditions, 8.5 moles of beta-carotene would provide a vitamin A quantity equivalent to 1 mole of preformed vitamin A. On a mass basis, 15.9 microg of beta-carotene was equivalent to 1 microg of retinol. The total administered beta-carotene was found to be 55 % absorbed by AMS analysis of cumulative stool.The co-administration of D6 beta-carotene and D6 retinyl acetate provides a technique for assessing individual ability to process beta-carotene to vitamin A. The results indicate that a single time point taken between 11-98 h after dose administration may provide a reliable value for the relative ratio of the two forms of vitamin A. However, results from more subjects are needed to assess the general utility of this method.

The vitamin A activity of beta-carotene is variable and surprisingly low in women. The reasons for this are not well understood. The vitamin A activity of beta-carotene in men is still uncertain. Contributions of dietary factors compared with individual traits are largely unknown.Our objective was to measure the intrinsic variability in the vitamin A activity of beta-carotene among healthy, well-fed men living in a controlled environment.We used a double-tracer test-retest design. We dosed 11 healthy men orally with 30 micromol hexadeuterated (D6) retinyl acetate (all-trans-19,19,19,20,20,20-[2H6]retinyl acetate) and then with 37 micromol D6 beta-carotene (19,19,19,19',19',19'-[2H6]beta-carotene) 1 wk later. Doses were taken with breakfasts containing 16 g fat. We measured D6 retinol, D6 beta-carotene, and trideuterated (D3) retinol (derived from D6 beta-carotene) concentrations in plasma. Areas under the plasma concentration x time since dosing curves (AUCs) were determined for D6 retinol, D6 beta-carotene, and D3 retinol.All men had detectable D6 retinol concentrations in plasma. The mean (+/-SE) absorption of D6 beta-carotene in all subjects was 2.235 +/- 0.925%, and the mean conversion ratio was 0.0296 +/- 0.0108 mol retinol to 1 mol beta-carotene. Only 6 of 11 men had sufficient plasma concentrations of D6 beta-carotene and D3 retinol that we could measure. The mean absorption of D6 beta-carotene in these 6 subjects was 4.097 +/- 1.208%, and the mean conversion ratio was 0.0540 +/- 0.0128 mol retinol to 1 mol beta-carotene.The vitamin A activity of beta-carotene, even when measured under controlled conditions, can be surprisingly low and variable.

We describe an improved whole blood folate analysis method that facilitates increased throughput compared to our previous method (Dueker et al. (2000) Anal. Biochem. 283, 266). Improvements include three items: first, a buffered solvent exchange to remove interfering amino acids, especially phenylalanine whose esters may interfere with the analysis because their retention times on the gas chromatography are close to those of the para-aminobenzoic acid (pABA) isotopomers; second, substituting an NH2 solid phase extraction step for an HPLC step permits the batch parallel processing of samples; third, replacing trifluoroacetyl derivatives of ethyl-esterified pABA isotopomers with heptafluorobutyl derivatives, which are better resolved on the GC column. The method measures pABA, a stable degradation product of folate. This simplifies sample handling and purification. Relative standard deviations are typically 5% or less and a single operator can process samples in batches of 40. Results from our GCMS method correlate (R = 0.98) with the Lactobacillus casei assay for whole blood folate. The modifications will facilitate the development of high throughput methods for whole blood folate. Our method holds promise for epidemiological and clinical studies, where accurate whole blood folate concentrations are needed. Because it is internally standardized, interlaboratory variation should be minimal.