Numerical simulation of heat transfer performance of spiral wound heat exchanger under sloshing condition.

LNG floating production storage and offloading (FPSO) unit is a new type of floating production unit developed for offshore natural gas fields. It performs the functions of natural gas extraction, pretreatment, liquefaction, and storage. In this study, the heat transfer characteristics of a spiral-wound heat exchanger were studied using numerical simulations, which provides a basis for equipment selection and structural optimization of spiral-wound heat exchangers. The main research contents and conclusions are as follows. Under land-based simulation conditions, the heat transfer coefficient of the shell side of the spiral-wound heat exchanger decreases with an increase in the winding angle of the heat exchange tube, decreases with an increase in the spacing of the heat exchange tube, and increases with an increase in the outer diameter of the heat exchange tube. When the winding angle increased from 5° to 8°, the heat transfer coefficient decreased by 6.70%. The heat transfer coefficient of the shell side decreased by 13.21% when the heat exchange tube spacing increased from 14 to 17 mm. The heat transfer coefficient of the shell side increased by 22.89% when the outer diameter of the heat exchange tube increased from 9 to 12 mm. When the sloshing angle is constant, the heat transfer coefficient of the spiral-wound heat exchanger decreases with an increase in the winding angle and spacing of the heat exchange tubes, and increases with an increase in the outer diameter of the heat exchange tubes. When the structural parameters of the heat exchanger are constant, the heat transfer coefficient decreases as the sloshing angle increases. When the sloshing angle was less than 3°, the sloshing promoted heat transfer on the shell side. When the sloshing angle was higher than 7°, the heat transfer effect of the shell side deteriorated considerably, which weakened the heat transfer performance of the heat exchanger. When the sloshing period is constant, the heat transfer coefficient of the wound heat exchanger decreases with an increase in the winding angle and spacing of the heat exchange tubes, and increases with an increase in the outer diameter of the heat exchange tubes. When the structural parameters of the heat exchanger are constant, the heat transfer coefficient increases with sloshing period. When the sloshing period was greater than 15 s, the influence of sloshing on the heat transfer on the shell side of the heat exchanger was relatively weak.

Multi-omics data provide insight into the adaptation of the glasshouse plant Rheum nobile to the alpine subnival zone.

Subnival glasshouse plants provide a text-book example of high-altitude adaptation with reproductive organs enclosed in specialized semi-translucent bracts, monocarpic reproduction and continuous survival under stress. Here, we present genomic, transcriptomic and metabolomic analyses for one such plant, the Noble rhubarb (Rheum nobile). Comparative genomic analyses show that an expanded number of genes and retained genes from two recent whole-genome duplication events are both relevant to subnival adaptation of this species. Most photosynthesis genes are downregulated within bracts compared to within leaves, and indeed bracts exhibit a sharp reduction in photosynthetic pigments, indicating that the bracts no longer perform photosynthesis. Contrastingly, genes related to flavonol synthesis are upregulated, providing enhanced defense against UV irradiation damage. Additionally, anatomically abnormal mesophyll combined with the downregulation of genes related to mesophyll differentiation in bracts illustrates the innovation and specification of the glass-like bracts. We further detect substantial accumulation of antifreeze proteins (e.g. AFPs, LEAs) and various metabolites (e.g. Proline, Protective sugars, procyanidins) in over-wintering roots. These findings provide new insights into subnival adaptation and the evolution of glasshouse alpine plants.

Genomic divergence and introgression among three Populus species.

Genomic divergence with gene flow is very common in both plants and animals. However, divergence and gene flow are two counteracting factors during speciation. Identifying the types of genes that are likely to be introgressed and what genetic factors restrict further effective reproduction of interspecific hybrids is of great interest to biologists. We aimed to address these issues using three related tree species, Populus alba (Pa), P. tremula (Pt), and P. tremuloides (Ps), and the interspecific hybrid of the former two species, P. × canescens (Pc). We collected 105 genomes for these four poplar lineages, including 28 Pa, 38Pt, 21 Ps, and 18 Pc individuals, to reconstruct their evolutionary histories. Our coalescence-based simulations indicated that Pa diverged earliest from Ps and Pt, and asymmetrical gene flow existed between any two lineages, with especially large ancient gene flow occurring between Pa and Pt. The genomic landscape of divergence between pairs of the three species are highly heterogeneous, which may have arisen through both divergent sorting of ancient polymorphisms and ongoing gene flow. We found that extant regions of the genome with introgressed ancestry reduced genetic divergence but elevated recombination rates and accounted for 5.76 % of the total genome. Introgressed genes were functionally associated with stress resistance, including innate immune response, anti-adversity response, and programmed cell death. However, candidate genes underlying postmating barriers of Pc were homozygous and resistant to introgression due to the incompatibility of alleles between loci after hybridization and were associated with endosperm and gamete formation and disease resistance. Our study revealed genomic dynamics during speciation with gene flow and identified regions of the genome that were likely introgressed and adaptive as well as candidate loci responsible for hybrid incompatibility that resulted in the formation of postmating barriers after hybridization.

Karyotype evolution of the Asterids insights from the first genome sequences of the family Cornaceae.

Cornaceae is a core representative family in Cornales, the earliest branching lineage in the Asterids on the life tree of angiosperms. This family includes the only genus Cornus, a group of ~55 species. These species occur widely in Northern Hemisphere and have been used as resources for horticultural ornaments, medicinal and industrial manufacturing. However, no any genome sequences are available for this family. Here, we reported a chromosome-level genome for Cornus controversa. This was generated using high-fidelity plus Hi-C sequencing, and totally ~771.80 Mb assembled sequences and 39,886 protein-coding genes were obtained. We provided evidence for a whole-genome duplication event (WGD) unique to C. controversa. The evolutionary features of this genome indicated that the expanded and unique genes might have contributed to response to stress, stimulus and defense. By using chromosome-level syntenic blocks shared between eight living genomes, we found high degrees of genomic diversification from the ancestral core-eudicot genome to the present-day genomes, suggesting an important role of WGD in genomic plasticity that leads to speciation and diversification. These results provide foundational insights on the evolutionary history of Cornaceae, as well as on the Asterids diversification.

Delimiting 33 Carpinus (Betulaceae) species with a further phylogenetic inference.

Carpinus (Betulaceae) has approximately 52 species distributed in the Northern Hemisphere, with many species of Carpinus found in China. However, the species boundaries and phylogenetic relationships remain poorly understood. This study reported ITS sequences for 225 individuals of 33 Carpinus species, mainly from China. We also included eight Ostrya species in our analyses, the closely related sister group of Carpinus. We aimed to delimit these species based on ITS sequences and clarify their phylogenetic relationships by constructing tree-like topology and networks at population level. We found that only 17 of 33 species could be delimited from the closely related ones based on species-specific mutations in ITS sequence variation, including all species of sect. Distegocarpus, and sect. Carpinus subsect. Carpinus. Carpinus subsect. Carpinus contained two endangered species, although one seemed to be a recently originated allopolyploid species with genetic additivity from two likely parents in the ITS sequence variation. Sixteen species of sect. Carpinus subsect. Polyneurae were classified into three species complexes, in each of which two or more could be not distinguished from each other. The closely related species of these complexes may still diverge at the early stage without genetic distinction in the nuclear ITS sequences because of too short of divergence time and frequent gene flow. Otherwise, some species may be established based on the intraspecific variations without genetic bases for an independently evolving unit.

Genomes and demographic histories of the endangered Bretschneidera sinensis (Akaniaceae).

BACKGROUND: Bretschneidera sinensis is an endangered relic tree species in the Akaniaceae family and is sporadically distributed in eastern Asia. As opposed to its current narrow and rare distribution, the fossil pollen of B. sinensis has been found to be frequent and widespread in the Northern Hemisphere during the Late Miocene. B. sinensis is also a typical mycorrhizal plant, and its annual seedlings exhibit high mortality rates in absence of mycorrhizal development. The chromosome-level high-quality genome of B. sinensis will help us to more deeply understand the survival and demographic histories of this relic species. RESULTS: A total of 25.39 Gb HiFi reads and 109.17 Gb Hi-C reads were used to construct the chromosome-level genome of B. sinensis, which is 1.21 Gb in length with the contig N50 of 64.13 Mb and chromosome N50 of 146.54 Mb. The identified transposable elements account for 55.21% of the genome. A total of 45,839 protein-coding genes were predicted in B. sinensis. A lineage-specific whole-genome duplication was detected, and 7,283 lineage-specific expanded gene families with functions related to the specialized endotrophic mycorrhizal adaptation were identified. The historical effective population size (Ne) of B. sinensis was found to oscillate greatly in response to Quaternary climatic changes. The Ne of B. sinensis has decreased rapidly in the recent past, making its extant Ne extremely lower. Our additional evolutionary genomic analyses suggested that the developed mycorrhizal adaption might have been repeatedly disrupted by environmental changes caused by Quaternary climatic oscillations. The environmental changes and an already decreased population size during the Holocene may have led to the current rarity of B. sinensis. CONCLUSION: This is a detailed report of the genome sequences for the family Akaniaceae distributed in evergreen forests in eastern Asia. Such a high-quality genomic resource may provide critical clues for comparative genomics studies of this family in the future.

The Chloranthus sessilifolius genome provides insight into early diversification of angiosperms.

Most extant angiosperms belong to Mesangiospermae, which comprises eudicots, monocots, magnoliids, Chloranthales and Ceratophyllales. However, phylogenetic relationships between these five lineages remain unclear. Here, we report the high-quality genome of a member of the Chloranthales lineage (Chloranthus sessilifolius). We detect only one whole genome duplication within this species and find that polyploidization events in different Mesangiospermae lineage are mutually independent. We also find that the members of all floral development-related gene lineages are present in C. sessilifolius despite its extremely simplified flower. The AP1 and PI genes, however, show a weak floral tissue-specialized expression. Our phylogenomic analyses suggest that Chloranthales and magnoliids are sister groups, and both are together sister to the clade comprising Ceratophyllales and eudicots, while the monocot lineage is sister to all other Mesangiospermae. Our findings suggest that in addition to hybridization, incomplete lineage sorting may largely account for phylogenetic inconsistencies between the observed gene trees.

Gains or losses? A quantitative estimation of environmental and economic effects of an ecological compensation policy.

Ecological compensation is an innovative and effective tool to explore the coordinated development of socioeconomic prosperity and ecological protection, especially for a watershed crossing different regions. It converts the externalities of ecosystem services into practical financial incentives for local stakeholders. This empirical study applies a quantitative policy evaluation approach to evaluate the environmental and economic effects of an ecological compensation policy, using the paddy land-to-dry land (PLDL) program implemented in China's Miyun Reservoir watershed as an example. The study is based on responses to a 2017 questionnaire regarding agricultural production inputs and outputs administered to 269 households in Hebei Province, where the PLDL program has been operational for over 10 yr. The results show that the program has reduced nitrogen usage by 24% on average in 2017 and decreased the total nitrogen emission load by 16.98 tons for the entire case area, which accounts for approximately 18.6% of the total nitrogen load reduction of the Miyun Reservoir basin. However, the upstream households involved in this program have experienced agricultural income losses higher than that allowed for by the current compensation criterion. Therefore, this paper discusses the factors that should be considered in the process of determining ecological compensation criteria. In particular, the paper proposes a differential compensation scheme based on the environmental effect at the individual level to avoid a standard payment for all households irrespective of their different contributions. This differential compensation payment scheme facilitates the fair treatment of environmental contributors and maximizes environmental benefits through an equitable allocation of limited ecological compensation funds. This study serves as a theoretical and practical reference for further improvement of the current ecological compensation policy in China. The study also sheds light on practices for estimating ecological compensation criteria and formulating ecological compensation policies for other regions or countries in the future.

Neferine induces apoptosis by modulating the ROS­mediated JNK pathway in esophageal squamous cell carcinoma.

Current treatments for esophageal squamous cell carcinoma (ESCC) have limited efficacy. Therefore, the development of novel therapeutic targets to effectively manage the disease and boost survival rates is imperative Neferine, a natural product extracted from Nelumbo nucifera (lotus) leaves, has been revealed to inhibit the growth of hepatocarcinoma, breast cancer and lung cancer cells. However, its effect on ESCC is unknown. In the present study, it was revealed that neferine exerted anti­proliferative effects in ESCC. It was also revealed that it triggered arrest of the G2/M phase and enhanced apoptosis of ESCC cell lines. Moreover, its ability to trigger accumulation of reactive oxygen species (ROS) and activate the c­Jun N­terminal kinase (JNK) pathway was demonstrated. Further study revealed how N­acetyl cysteine (NAC), a ROS inhibitor, attenuated these effects, demonstrating that ROS and JNK inhibitors mediated a marked reversal of neferine­triggered cell cycle arrest and apoptosis in ESCC cells. Finally, it was revealed that neferine was involved in the inhibition of Nrf2, an antioxidant factor. Collectively, these findings demonstrated the antitumor effect of neferine in ESCC, through the ROS­mediated JNK pathway and inhibition of Nrf2, indicating its potential as a target for development of novel and effective therapeutic agents against ESCC.

[Dynamics of Epilithic Algae Communities and Their Relationship with Environmental Factors During Storage and Non-storage Periods in the Three Gorges Reservoir].

In order to explore the composition of epiphytic algae and its related environmental factors, 12 sampling sites in the natural reaches and the backwater reaches (including perennial backwater sections and fluctuating backwater sections) were investigated among tributaries of the Caotang River, the Meixi River, and the Daxi River in the Fengjie district of the Chongqing section of the Three Gorges Reservoir under different hydrological regimes (i.e., storage and non-storage periods). Results showed that 103 species of epilithic algae belonging to 45 genera and 4 families are found in the 3 tributaries. This included 67 species belonging to 34 genus in the natural sections and 82 species (64 species in perennial backwater sections and 41 species in fluctuating backwater sections) belonging to 34 genera in the backwater sections. During the storage period, the dominant species in the natural sections were Melosira varians, Cocconeis placentula, Diatoma vulgure, Gyrosigma scalproides, and Oscillatoria tenuis, while the dominant species in the backwater sections were M. varians, Cymbella affinis,D. vulgure, Eucapsis alpina, and M. granulata. During the non-storage period, the dominant species in the natural sections were M. varians, C. affinis, and C. placentula, whereas the dominant species in the backwater sections were O. princeps, O. rupicola,O. formosa, Synedra acus, Ulothrix sp., Merismopedia elegans, and O. tenuis. These results suggested that the compositions of dominant species showed significant differences during the non-storage period, while little difference was found during the storage period. In addition, the dominant species did not show a significant change in the natural sections, but a marked difference was observed in the backwater sections. Similar dominant species were observed in both perennial and fluctuating backwater sections during the non-storage period, but significantly different dominant species were found during the storage period. Redundancy analysis suggested that the composition of epilithic algae was influenced by different environmental factors, such as temperature, electrical conductivity, pH, total nitrogen, and total phosphorus. Indeed, changes in the cell densities of dominant algae at the different sites were mainly affected by temperature and the concentrations of nitrogen and phosphorus. These results suggest that the different hydrological regimes had an important role not only on the reservoir water environment, but also the dynamics of epilithic algal communities.

Physiological and transcriptomic analyses to determine the responses to phosphorus utilization in Nostoc sp.

Phosphorus (P) is an important factor driving algal growth in aquatic ecosystems. In the present study, the growth, P uptake and utilization, photosynthesis, and transcriptome profile of Nostoc sp. were measured when Nostoc sp. cultured in media containing ß-glycerol phosphate (ß-gly, containing COP bonds), 2-aminoethylphosphonic acid (2-amin, containing CP bonds), or orthophosphate (K2HPO4), and in P-free (NP) medium. The results revealed that NP treatment adversely affected the growth and photosynthesis of Nostoc sp. and significantly down-regulated the expression of genes related to nutrient transport and material metabolism. Furthermore, 2-amin treatment reduced the growth of Nostoc sp. but did not significantly reduce photosynthesis, and the treatments of NP and 2-amin up-regulated the expressions of genes related antioxidation and stress. Additionally, there were no obvious differences in growth, photosynthesis, and phosphorus utilization between the ß-gly and K2HPO4 treatments. These results suggested that Nostoc had a flexible ability to utilize P, which might play an important role in its widespread distribution in the environment.

Plasmacytoid Dendritic Cells and Infected Cells Form an Interferogenic Synapse Required for Antiviral Responses.

Type I interferon (IFN-I) is critical for antiviral defense, and plasmacytoid dendritic cells (pDCs) are a predominant source of IFN-I during virus infection. pDC-mediated antiviral responses are stimulated upon physical contact with infected cells, during which immunostimulatory viral RNA is transferred to pDCs, leading to IFN production via the nucleic acid sensor TLR7. Using dengue, hepatitis C, and Zika viruses, we demonstrate that the contact site of pDCs with infected cells is a specialized platform we term the interferogenic synapse, which enables viral RNA transfer and antiviral responses. This synapse is formed via αLß2 integrin-ICAM-1 adhesion complexes and the recruitment of the actin network and endocytic machinery. TLR7 signaling in pDCs promotes interferogenic synapse establishment and provides feed-forward regulation, sustaining pDC contacts with infected cells. This interferogenic synapse may allow pDCs to scan infected cells and locally secrete IFN-I, thereby confining a potentially deleterious response.

Aramid Nanomaterials of Various Morphologies: Preparation and Mechanical Property Enhancement.

Aramid nanofibers (ANFs) are a novel type of promising nanoscale building blocks for high-performance nanocomposites. Conventionally, ANFs are used to composite with polymers containing polar groups such as -OH and -NH2 since those polymers can interact with the amide groups in ANFs through polar-polar interaction such as hydrogen bonding. In this study, ANFs were derivatized with non-polar alkyl groups including ethyl, octyl and dodecyl groups and used as a performance-enhancing additive to polyvinyl chloride (PVC) with weak polarity. Interestingly, it was observed that the morphologies of the resulting alkyl-derivatized aramid nanomaterials (R-ANMs) varied significantly including nanofibers, nanobranches, nanosheets, and nanospheres, all of which depended on the degree of substitution (DS) and the chain length of the alkyl group. As an additive, R-ANMs improved the Young's modulus, toughness and yield strength of the PVC films. This study proves the concept that ANFs can be used to composite weakly polar or non-polar polymers.

Chlorophyll a fluorescence and transcriptome reveal the toxicological effects of bisphenol A on an invasive cyanobacterium, Cylindrospermopsis raciborskii.

Bisphenol A has attracted worldwide attention due to its harmful effects on humans, animals and plants. In this study, the toxicological effects of BPA on Cylindrospermopsis raciborskii were assessed based on chlorophyll a fluorescence and transcriptome analyses. The results showed that the growth of C. raciborskii was significantly inhibited when BPA exceeded 0.1 mg L-1. A marked rise of phase J was observed at a concentration greater than 0.1 mg L-1, while a K phase appeared at 20 mg L-1. The chlorophyll a fluorescence parameters of RC/CS0, F0, φP0, φE0, and ψ0, underwent a significant decline under all treatments of BPA, whereas a significant increase in both VJ and M0 occurred under all concentrations of BPA. Additionally, ABS/RC and DIo/RC markedly increased at 10 mg L-1 and 20 mg L-1. The transcriptome analysis revealed that the genes of photosynthesis, including psbA, psbB, psbC, psbD, apcA, apcB, cpcA, and cpcB, as well as those of chlorophyll and carotenoid biosynthesis, namely hemN, acsF, chlL, chlN, chlP, crtB, pds, were all down-regulated. Moreover, BPA also inhibited the oxidative phosphorylation, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), and fatty acid metabolism in C. raciborskii. Taken together, these results suggest BPA can negatively affect the expression of multiple genes and the vital energy metabolism process to arrest the growth and photosynthesis of C. raciborskii.

The Effect of Bisphenol A on Growth, Morphology, Lipid Peroxidation, Antioxidant Enzyme Activity, and PS II in Cylindrospermopsis raciborskii and Scenedesmus quadricauda.

To investigate the effect of bisphenol A (BPA) on Cylindrospermopsis raciborskii (Cyanobacteria) and Scenedesmus quadricauda (Chlorophyta), we grew the two species at BPA concentrations of 0, 0.1, 1, 2, 5, 10, and 20 mg/L and examined their growth, lipid peroxidation, antioxidant enzyme activity, and chlorophyll a fluorescence. The 96-h EC50 values (effective concentration causing 50% growth inhibition) for BPA in C. raciborskii and S. quadricauda were 9.663 ± 0.047, and 13.233 ± 0.069 mg/L, respectively. A significant reduction in chlorophyll a concentration was found in C. raciborskii and S. quadricauda when BPA concentrations were greater than 1 and 2 mg/L, respectively. Furthermore, F v/F m, ΔF/F m', and qP decreased significantly at 10 mg/L BPA in C. raciborskii but started to decrease at 10 mg/L in S. quadricauda. The changes in chlorophyll fluorescence parameters (α, rETRmax) that were obtained from the rapid light response curves of both algae species showed similar responses to F v/F m, ΔF/F m', and qP under BPA-induced stress. Values for all of the chlorophyll fluorescence parameters in S. quadricauda were higher than in C. raciborskii; however, the nonphotochemical quenching measured in C. raciborskii was considerably higher than it was in S. quadricauda. In addition, lipid peroxidation (determined as MDA content) and antioxidant enzyme activities (SOD and CAT) increased in both species as the BPA concentration increased. These results suggest that C. raciborskii is more sensitive to the effects of BPA than S. quadricauda and that photosystem II might be a target for the activity of BPA in vivo.

CAMSAP3 accumulates in the pericentrosomal area and accompanies microtubule release from the centrosome via katanin.

The epithelium has an apico-basal axis polarity that plays an important role in absorption, excretion and other physiological functions. In epithelial cells, a substantial number of non-centrosomal microtubules (MTs) are scattered in the cytoplasm with an apico-basal polarity and reorientate as epithelial cells perform different functions. Several previous studies have found that non-centrosomal MTs are nucleated at the centrosome, and then released and translocated elsewhere. However, the detailed process and molecular mechanism remain largely unknown. In this study, we found that Nezha, also called calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a non-centrosomal MT minus-end protein, accumulates in the pericentrosomal area and accompanies the release of MTs from the centrosome; whereas depletion of CAMSAP3 prevented MT release and instead caused focusing of MTs at centrosomes. Further studies demonstrated that CAMSAP3 precisely coordinates with dynein and katanin to regulate the MT detachment process. In conclusion, our results indicate that CAMSAP3 is a key molecule for generation of non-centrosomal MTs.

[Functional Group Characteristics of Planktonic Diatoms and Their Relationship with Environmental Factors in the Ruxi River].

To elucidate the functional group characteristics of planktonic diatoms and their relationship with environment factors in the Ruxi River, multivariate statistical analysis and functional group classification were conducted in this study. The success pattern of a diatom functional group and its driving factor were analyzed for the Ruxi River, a typical tributary of Three Gorges Reservoir, after the phytoplankton community and environmental variables were investigated at three different stages: level water period (April 2014), dry season (December 2014), and wet season (July 2014), based on the characteristic of water level. The results showed that there were 10 diatom functional groups in the Ruxi River: the A, B, C, D, Lo, MP, P, TB, X3, and S1 groups, and among them, MP was the most groups, but the dominant group was D group. Stepwise multiple regression analysis indicated that ρ(TN) in the water column was the primary factor significantly affecting the densities in the normal water period, whereas turbidity, alkalinity, and pH significantly influenced the functional group densities in the normal water period. In the high water period, however, transparency was the most important environmental factor affecting the functional group densities. Additionally, the results of RDA analysis found that water temperature, electrical conductivity (Spc), oxidation-reduction potential (ORP), ρ(DO), and ρ(NO3--N) were the main environmental factors that influenced the diversity of diatom functional groups in the Ruxi River. These results suggested that functional groups could well reflect the habitat characteristics of the Ruxi River and the effect of the nutrient element, nitrogen, to the success of phytoplankton functional groups and changes of water quality in the Ruxi River should be paid more attention.

Separation and purification of astaxanthin from Phaffia rhodozyma by preparative high-speed counter-current chromatography.

An effective high-speed counter-current chromatography (HSCCC) method was established for the preparative isolation and purification of astaxanthin from Phaffia rhodozyma. With a two-phase solvent system composed of n-hexane-acetone-ethanol-water (1:1:1:1, v/v/v/v), 100mg crude extract of P. rhodozyma was separated to yield 20.6mg of astaxanthin at 92.0% purity. By further one step silica gel column chromatography, the purity reached 99.0%. The chemical structure of astaxanthin was confirmed by thin layer chromatography (TLC), UV spectroscopy scanning, high performance liquid chromatography with a ZORBAX SB-C18 column and a Waters Nova-pak C18 column, and ESI/MS/MS.

Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.

Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters.

Metabolomic analysis reveals metabolic changes caused by bisphenol A in rats.

Bisphenol A (BPA) is a widely used material known to cause adverse effects in humans and other mammals. To date, little is known about the global metabolomic alterations caused by BPA using urinalysis. Sprague-Dawley rats were orally administrated BPA at the levels of 0, 0.5 µg/kg/day and 50 mg/kg/day covering a low dose and a reference dose for 8 weeks. We conducted a capillary electrophoresis in tandem with electrospray ionization time-of-flight mass spectrometry based nontargeted metabolomic analysis using rat urine. To verify the metabolic alteration at both low and high doses, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were further conducted to analyze hepatic expression of methionine adenosyltransferase Iα (Mat1a) and methionine adenosyltransferase IIα (Mat2a). Hepatic S-adenosylmethionine (SAMe) was also analyzed. A total of 199 metabolites were profiled. Statistical analysis and pathway mapping indicated that the most significant metabolic perturbations induced by BPA were the increased biotin and riboflavin excretion, increased synthesis of methylated products, elevated purine nucleotide catabolism, and increased flux through the choline metabolism pathway. We found significantly higher mRNA and protein levels of Mat1a and Mat2a, and significantly higher SAMe levels in rat liver at both low and high doses. These two genes encode critical isoenzymes that catalyze the formation of SAMe, the principal biological methyl donor involved in the choline metabolism. In conclusion, an elevated choline metabolism is underlying the mechanism of highly methylated environment and related metabolic alterations caused by BPA. The data of BPA-elevated accepted biomarkers of injury indicate that BPA induces DNA methylation damage and broad protein degradation, and the increased deleterious metabolites in choline pathway may also be involved in the toxicity of BPA.