Genomic Insights into High-Altitude Adaptation: A Comparative Analysis of Roscoea alpina and R. purpurea in the Himalayas.

Environmental stress at high altitudes drives the development of distinct adaptive mechanisms in plants. However, studies exploring the genetic adaptive mechanisms of high-altitude plant species are scarce. In the present study, we explored the high-altitude adaptive mechanisms of plants in the Himalayas through whole-genome resequencing. We studied two widespread members of the Himalayan endemic alpine genus Roscoea (Zingiberaceae): R. alpina (a selfing species) and R. purpurea (an outcrossing species). These species are distributed widely in the Himalayas with distinct non-overlapping altitude distributions; R. alpina is distributed at higher elevations, and R. purpurea occurs at lower elevations. Compared to R. purpurea, R. alpina exhibited higher levels of linkage disequilibrium, Tajima's D, and inbreeding coefficient, as well as lower recombination rates and genetic diversity. Approximately 96.3% of the genes in the reference genome underwent significant genetic divergence (FST ≥ 0.25). We reported 58 completely divergent genes (FST = 1), of which only 17 genes were annotated with specific functions. The functions of these genes were primarily related to adapting to the specific characteristics of high-altitude environments. Our findings provide novel insights into how evolutionary innovations promote the adaptation of mountain alpine species to high altitudes and harsh habitats.

Phylotranscriptomic analyses reveal deep gene tree discordance in Camellia (Theaceae).

Gene tree discordance is a significant legacy of biological evolution. Multiple factors can result in incongruence among genes, such as introgression, incomplete lineage sorting (ILS), gene duplication or loss. Resolving the background of gene tree discordance is a critical way to uncover the process of species diversification. Camellia, the largest genus in Theaceae, has controversial taxonomy and systematics due in part to a complex evolutionary history. We used 60 transcriptomes of 55 species, which represented 15 sections of Camellia to investigate its phylogeny and the possible causes of gene tree discordance. We conducted gene tree discordance analysis based on 1,617 orthologous low-copy nuclear genes, primarily using coalescent species trees and polytomy tests to distinguish hard and soft conflict. A selective pressure analysis was also performed to assess the impact of selection on phylogenetic topology reconstruction. Our results detected different levels of gene tree discordance in the backbone of Camellia, and recovered rapid diversification as one of the possible causes of gene tree discordance. Furthermore, we confirmed that none of the currently proposed sections of Camellia was monophyletic. Comparisons among datasets partitioned under different selective pressure regimes showed that integrating all orthologous genes provided the best phylogenetic resolution of the species tree of Camellia. The findings of this study reveal rapid diversification as a major source of gene tree discordance in Camellia and will facilitate future investigation of reticulate relationships at the species level in this important plant genus.

Phylotranscriptomics of Theaceae: generic-level relationships, reticulation and whole-genome duplication.

BACKGROUND AND AIMS: Theaceae, with three tribes, nine genera and more than 200 species, are of great economic and ecological importance. Recent phylogenetic analyses based on plastomic data resolved the relationships among the three tribes and the intergeneric relationships within two of those tribes. However, generic-level relationships within the largest tribe, Theeae, were not fully resolved. The role of putative whole-genome duplication (WGD) events in the family and possible hybridization events among genera within Theeae also remain to be tested further. METHODS: Transcriptomes or low-depth whole-genome sequencing of 57 species of Theaceae, as well as additional plastome sequence data, were generated. Using a dataset of low-copy nuclear genes, we reconstructed phylogenetic relationships using concatenated, species tree and phylogenetic network approaches. We further conducted molecular dating analyses and inferred possible WGD events by examining the distribution of the number of synonymous substitutions per synonymous site (Ks) for paralogues in each species. For plastid protein-coding sequences , phylogenies were reconstructed for comparison with the results obtained from analysis of the nuclear dataset. RESULTS: Based on the 610 low-copy nuclear genes (858 606 bp in length) investigated, Stewartieae was resolved as sister to the other two tribes. Within Theeae, the Apterosperma-Laplacea clade grouped with Pyrenaria, leaving Camellia and Polyspora as sister. The estimated ages within Theaceae were largely consistent with previous studies based mainly on plastome data. Two reticulation events within Camellia and one between the common ancestor of Gordonia and Schima were found. All members of the tea family shared two WGD events, an older At-γ and a recent Ad-ß; both events were also shared with the outgroups (Diapensiaceae, Pentaphylacaceae, Styracaceae and Symplocaceae). CONCLUSIONS: Our analyses using low-copy nuclear genes improved understanding of phylogenetic relationships at the tribal and generic levels previously proposed based on plastome data, but the phylogenetic position of the Apterosperma-Laplacea clade needs more attention. There is no evidence for extensive intergeneric hybridization within Theeae or for a Theaceae-specific WGD event. Land bridges (e.g. the Bering land bridge) during the Late Oligocene may have permitted the intercontinental plant movements that facilitated the putative ancient introgression between the common ancestor of Gordonia and Schima.

Speciation along the elevation gradient: Divergence of Roscoea species within the south slope of the Himalayas.

The Himalayas with dramatic elevation gradient is one of the global biodiversity hotspots. Although origin of biodiversity of the Himalayas is of great concern, the speciation process within the Himalayas is poorly known. Roscoea within the Himalayas serve as a good model system to test the speciation process along an elevation gradient. 32,375 unlinked SNPs were used to reconstruct phylogenetic relationships and introgression analyses in D-statistics and Fastsimicoal2. Species distribution modeling (SDM) was used to simulate habitat shift of Roscoea species during climate changes. Phylogeny suggested that the speciation order, except R. capitata, was from highland to lowland. D-statistics analyses suggested significant bidirectional ancient introgression between elevation-neighboring clades but no introgression between R. capitata and othern clades and no introgression among extant species. Fastsimicoal2 suggested interspecific introgressions were asymmetric. SDM predicted that habitats of Roscoea shifted to low elevation during cooling age. These results suggested that the sudden uplift of the Himalayas likely promoted speciation by vicariance, and climate cooling drove species divergence towards lower elevation. This study provides explanations for the origin of biodiversity within the Himalayas, and an insight to understand speciation along elevation in the mountainous regions.

Water mediates fertilization in a terrestrial flowering plant.

Water-mediated fertilization is ubiquitous in early land plants. This ancestral mode of fertilization has, however, generally been considered to have been lost during the evolutionary history of terrestrial flowering plants. We investigated reproductive mechanisms in the subtropical ginger Cautleya gracilis (Zingiberaceae), which has two pollen conditions - granular and filiform masses - depending on external conditions. We tested whether rain transformed granular pollen into filiform masses and whether this then promoted pollen-tube growth and fertilization of ovules. Using experimental manipulations in the field we investigated the contribution of water-mediated fertilization to seed production. Rain caused granular pollen to form filiform masses of germinating pollen tubes, which transported sperm to ovules, resulting in fertilization and seed set. Flowers exposed to rain produced significantly more seeds than those protected from the rain, which retained granular pollen. Insect pollination made only a limited contribution to seed set because rainy conditions limited pollinator service. Our results reveal a previously undescribed fertilization mechanism in flowering plants involving water-mediated fertilization stimulated by rain. Water-mediated fertilization is likely to be adaptive in the subtropical monsoon environments in which C. gracilis occurs by ensuring reproductive assurance when persistent rain prevents insect-mediated pollination.

MiR-17-5p up-regulates YES1 to modulate the cell cycle progression and apoptosis in ovarian cancer cell lines.

MicroRNAs (miRNAs) are small, non-coding RNAs that participate in the regulation of gene expression. Although many studies have demonstrated the involvement of miR-17-5p in different cancers, little is known to its function in ovarian cancer. In this study, we demonstrated that overexpression of miR-17-5p was able to enhance cell proliferation by promoting G1/S transition of the cell cycle and suppressing apoptosis in ES-2 and OVCAR3 cell lines, whereas inhibition of miR-17-5p yielded the reverse phenotype. YES1 was identified as a novel target gene of miR-17-5p. Moreover, miR-17-5p was found to directly bind to the 3'UTR of YES1 mRNA and up-regulated its expression. Furthermore, knockdown of YES1 led to the suppression of proliferation and induced cell cycle arrest in ES-2 and OVCAR3 cells. Ectopic expression of YES1 was able to reverse the effects of miR-17-5p inhibition. Collectively, our results indicated that miR-17-5p might play a role in human ovarian cancer by up-regulating YES1 expression. J. Cell. Biochem. 116: 1050-1059, 2015. © 2015 Wiley Periodicals, Inc.

miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells.

MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate target gene expression, play an important role in cancer initiation, progression, and metastasis. However, the role of many miRNAs in cervical cancer is not fully understood. In this study, we found that miR-212 and miR-132 from the same gene cluster are downregulated in human cervical cancer tissues when compared with adjacent noncancerous tissues. The overexpression of miR-212/132 not only led to a delay in the G1/S phase transition and repressed cell proliferation but also resulted in an increase in E-cadherin expression and a decrease in vimentin, suppressing the epithelial to mesenchymal transition and migration and invasion in cervical cancer cells. Subsequently, SMAD2 was identified as a common target of miR-212/132 and was found to be negatively regulated by miR-212/132 at the mRNA and protein levels. Furthermore, SMAD2 silencing led to the same effect on cervical cancer cells as miR-212/132 overexpression. Importantly, SMAD2 overexpression partially reversed the cellular phenotypes induced by miR-212/132 overexpression. In conclusion, our study indicated that miR-212/132 functions as tumor suppressor by targeting SMAD2 in cervical cancer.

Phylogeny and historical biogeography of Isodon (Lamiaceae): rapid radiation in south-west China and Miocene overland dispersal into Africa.

Rapid organismal radiations occurring on the Qinghai-Tibetan Plateau (QTP) and the mechanisms underlying Asia-Africa intercontinental disjunctions have both attracted much attention from evolutionary biologists. Here we use the genus Isodon (Lamiaceae), a primarily East Asian lineage with disjunct species in central and southern Africa, as a case study to shed light upon these processes. The molecular phylogeny and biogeographic history of Isodon were reconstructed using sequences of three plastid markers, the nuclear ribosomal internal transcribed spacer (nrITS), and a low-copy nuclear gene (LEAFY intron II). The evolution of chromosome numbers in this genus was also investigated using probabilistic models. Our results support a monophyletic Isodon that includes the two disjunct African species, both of which likely formed through allopolyploidy. An overland migration from Asia to Africa through Arabia during the early Miocene is proposed as the most likely explanation for the present disjunct distribution of Isodon. The opening of the Red Sea in the middle Miocene may appear to have had a major role in disrupting floristic exchange between Asia and Africa. In addition, a rapid radiation of Isodon was suggested to occur in the late Miocene. It corresponds with one of the major uplifts of the QTP and subsequent aridification events. Our results support the hypothesis that geological and climatic events play important roles in driving biological diversification of organisms distributed in the QTP area.

Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.

Codon usage bias in chloroplast genes implicate adaptive evolution of four ginger species.

Codon usage bias (CUB) refers to different codons exhibiting varying frequencies of usage in the genome. Studying CUB is crucial for understanding genome structure, function, and evolutionary processes. Herein, we investigated the codon usage patterns and influencing factors of protein-coding genes in the chloroplast genomes of four sister genera (monophyletic Roscoea and Cautleya, and monophyletic Pommereschea and Rhynchanthus) from the Zingiberaceae family with contrasting habitats in southwestern China. These genera exhibit distinct habitats, providing a unique opportunity to explore the adaptive evolution of codon usage. We conducted a comprehensive analysis of nucleotide composition and codon usage on protein-coding genes in the chloroplast genomes. The study focused on understanding the relationship between codon usage and environmental adaptation, with a particular emphasis on genes associated with photosynthesis. Nucleotide composition analysis revealed that the overall G/C content of the coding genes was ˂ 48%, indicating an enrichment of A/T bases. Additionally, synonymous and optimal codons were biased toward ending with A/U bases. Natural selection is the primary factor influencing CUB characteristics, particularly photosynthesis-associated genes. We observed differential gene expressions related to light adaptation among sister genera inhabiting different environments. Certain codons were favored under specific conditions, possibly contributing to gene expression regulation in particular environments. This study provides insights into the adaptive evolution of these sister genera by analyzing CUB and offers theoretical assistance for understanding gene expression and regulation. In addition, the data support the relationship between RNA editing and CUB, and the findings shed light on potential research directions for investigating adaptive evolution.

Species discrimination in Schima (Theaceae): Next-generation super-barcodes meet evolutionary complexity.

Plastid genome and nuclear ribosomal DNA (nrDNA) arrays, proposed recently as "super-barcodes," might provide additional discriminatory power and overcome the limitations of traditional barcoding loci, yet super-barcodes need to be tested for their effectiveness in more plant groups. Morphological homoplasy among Schima species makes the genus a model for testing the efficacy of super-barcodes. In this study, we generated multiple data sets comprising standard DNA barcodes (matK, rbcL, trnH-psbA, nrITS) and super-barcodes (plastid genome, nrDNA arrays) across 58 individuals from 12 out of 13 species of Schima from China. No samples were correctly assigned to species using standard DNA barcodes and nrDNA arrays, while only 27.27% of species with multiple accessions were distinguished using the plastid genome and its partitioned data sets-the lowest estimated rate of super-barcode success in the literature so far. For Schima and other taxa with similarly recently divergence and low levels of genetic variation, incomplete lineage sorting, hybridization or taxonomic oversplitting are all possible causes of the failure. Taken together, our study suggests that by no means are super-barcodes immune to the challenges imposed by evolutionary complexity. We therefore call for developing multilocus nuclear markers for species discrimination in plant groups.

Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002).

PURPOSE: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy. PATIENTS AND METHODS: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses. RESULTS: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group. CONCLUSIONS: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.

Chloroplast Genome Evolution in Four Montane Zingiberaceae Taxa in China.

Chloroplasts are critical to plant survival and adaptive evolution. The comparison of chloroplast genomes could provide insight into the adaptive evolution of closely related species. To identify potential adaptive evolution in the chloroplast genomes of four montane Zingiberaceae taxa (Cautleya, Roscoea, Rhynchanthus, and Pommereschea) that inhabit distinct habitats in the mountains of Yunnan, China, the nucleotide sequences of 13 complete chloroplast genomes, including five newly sequenced species, were characterized and compared. The five newly sequenced chloroplast genomes (162,878-163,831 bp) possessed typical quadripartite structures, which included a large single copy (LSC) region, a small single copy (SSC) region, and a pair of inverted repeat regions (IRa and IRb), and even though the structure was highly conserved among the 13 taxa, one of the rps19 genes was absent in Cautleya, possibly due to expansion of the LSC region. Positive selection of rpoA and ycf2 suggests that these montane species have experienced adaptive evolution to habitats with different sunlight intensities and that adaptation related to the chloroplast genome has played an important role in the evolution of Zingiberaceae taxa.

Contrasting coarse and fine scale genetic structure among isolated relic populations of Kmeria septentrionalis.

Trees of the Magnoliaceae family are of scientific, cultural and socio-economic importance. Kmeria septentrionalis Dandy (Magnoliaceae) is a dioecious tree, found in small, isolated, relic populations in Southern China, and is subject to extensive protection due to its rarity and high economic values. To improve conservation outcomes and in particular, germplasm collection guidelines, information on spatial genetic structure of the species is required. In this study, we investigated the spatial genetic structure and genetic diversity of 161 individuals of K. septentrionalis collected from five natural populations using AFLP molecular markers. Within-population genetic variation was measured, with percentage of polymorphic bands (PPB) ranged from 63% to 87%, while H (S) (genetic diversity within population) varied from 0.185 to 0.244 with a mean of 0.215 ± 0.025. Significant genetic differentiations were revealed between pairwise populations, indicating each population existing as an independent evolutionarily significant unit. Mantel test results showed no pattern of isolation-by-distance among populations separated by large distance. Fine scale spatial patterns of genetic variation suggested significant effects of isolation-by-distance within population at distances of 22 m. The results of contrasting genetic structure at coarse and fine scale in K. septentrionalis may indicate restricted pollen flow and seed dispersal at fine scales, and separated evolution in isolated populations over long period of time at coarser scales. Finally, we make several suggestions for improved management practices that may assist in the conservation of this species.

The complete chloroplast genome sequence of Laplacea alpestris and its phylogenetic position.

Laplacea alpestris is a member of the genus Laplacea, which distributes in Central and South America. Genetic information of L. alpestris would provide guidance for the phylogenetic position of this species. Here, we reported and characterized its complete chloroplast (cp) genome using Illumina pair-end sequencing data. The total chloroplast genome size of this species was 157,211 bp, including inverted repeats (IRs) of 26,103 bp, separated by a large single copy (LSC) and a small single copy (SSC) of 86,749 and 18,256 bp, respectively. A total of 132 genes, including 37 tRNA, 8 rRNA, and 87 protein-coding genes were identified. Phylogenetic analysis showed that L. alpestris formed a monophyletic clade with Laplacea fruticosa, and then grouped with Apterosperma oblata. The systematic position of Southeast Asian Laplacea species needs further studies.

Landscape genomics provides evidence of climate-associated genetic variation in Mexican populations of Quercus rugosa.

Local adaptation is a critical evolutionary process that allows plants to grow better in their local compared to non-native habitat and results in species-wide geographic patterns of adaptive genetic variation. For forest tree species with a long generation time, this spatial genetic heterogeneity can shape the ability of trees to respond to rapid climate change. Here, we identify genomic variation that may confer local environmental adaptations and then predict the extent of adaptive mismatch under future climate as a tool for forest restoration or management of the widely distributed high-elevation oak species Quercus rugosa in Mexico. Using genotyping by sequencing, we identified 5,354 single nucleotide polymorphisms (SNPs) genotyped from 103 individuals across 17 sites in the Trans-Mexican Volcanic Belt, and, after controlling for neutral genetic structure, we detected 74 F ST outlier SNPs and 97 SNPs associated with climate variation. Then, we deployed a nonlinear multivariate model, Gradient Forests, to map turnover in allele frequencies along environmental gradients and predict areas most sensitive to climate change. We found that spatial patterns of genetic variation were most strongly associated with precipitation seasonality and geographic distance. We identified regions of contemporary genetic and climatic similarities and predicted regions where future populations of Q. rugosa might be at risk due to high expected rate of climate change. Our findings provide preliminary details for future management strategies of Q. rugosa in Mexico and also illustrate how a landscape genomic approach can provide a useful tool for conservation and resource management strategies.

Tertiary origin and pleistocene diversification of dragon blood tree (Dracaena cambodiana-Asparagaceae) populations in the Asian tropical forests.

BACKGROUND: The origin of extraordinarily rich biodiversity in tropical forests is often attributed to evolution under stable climatic conditions over a long period or to climatic fluctuations during the recent Quaternary period. Here, we test these two hypotheses using Dracaena cambodiana, a plant species distributed in paleotropical forests. METHODS: WE ANALYZED NUCLEOTIDE SEQUENCE DATA OF TWO CHLOROPLAST DNA (CPDNA: atpB-rbcL and trnD-trnT) regions and genotype data of six nuclear microsatellites from 15 populations (140 and 363 individuals, respectively) distributed in Indochina Peninsular and Hainan Island to infer the patterns of genetic diversity and phylogeographic structure. The population bottleneck and genetic drift were estimated based upon nuclear microsatellites data using the software programs BOTTLENECK and 2MOD. The lineage divergence times and past population dynamics based on cpDNA data were estimated using coalescent-based isolation-with-migration (IMa) and BEAST software programs. RESULTS: A significant phylogeographic structure (N ST = 0.876, G ST = 0.796, F ST-SSR = 0.329, R ST = 0.449; N ST>G ST, R ST>F ST-SSR, P<0.05) and genetic differentiation among populations were detected. Bottleneck analyses and Bayesian skyline plot suggested recent population reduction. The cpDNA haplotype network revealed the ancestral populations from the southern Indochina region expanded to northward. The most recent ancestor divergence time of D. cambodiana dated back to the Tertiary era and rapid diversification of terminal lineages corresponded to the Quaternary period. CONCLUSIONS: The results indicated that the present distribution of genetic diversity in D. cambodiana was an outcome of Tertiary dispersal and rapid divergence during the Quaternary period under limited gene flow influenced by the uplift of Himalayan-Tibetan Plateau and Quaternary climatic fluctuations respectively. Evolutionary processes, such as extinction-recolonization during the Pleistocene may have contributed to the fast diversification in D. cambodiana.

Estradiol pretreatment attenuated nicotine-induced endothelial cell apoptosis via estradiol functional membrane receptor.

Cigarette smoking is highly associated with increased cardiovascular disease complications. The female population, however, manifests reduced cardiovascular morbidity. We define nicotine's effect upon human umbilical vein endothelial cells (HUVECs), determine whether estradiol might ameliorate endothelial dysfunction via its membrane estrogen receptor (mER), and attempt to elucidate the underlying mechanisms. Endothelial cells were pretreated with estradiol-BSA and measured resultant ion flux across the cells via the patch clamp technique to assess mER is functionality. Estradiol-BSA administration was associated with 30% decreased nicotine-induced apoptosis and also attenuated nicotine-activated phosphorylation of p38 and ERK. Pretreatment of estradiol-BSA triggered a low calcium influx, suggesting ahead low influx calcium played a critical role in the underlying protective mechanisms of estradiol. Furthermore, this estradiol-BSA protection against apoptosis remained effective in the presence of tamoxifen, an intracellular estrogen receptor (iER) inhibitor. Additionally, tamoxifen did not abolish estradiol-BSA's inhibitory effect upon p38 and ERK's activation, giving evidence to the obligatory role of p38 and ERK signaling in the estradiol-BSA's anti-apoptotic action via mER. Our study provides evidence that nicotine enhances endothelial cell apoptosis, but estrogen exerts anti-apoptotic effect through its functional membrane estrogen receptor. Clinically, the nicotine in cigarettes might contribute to endothelial dysfunction, whereas ambient estradiol may provide cellular protection against nicotine-induced injury through its functional membrane receptor via MAPK pathway downregulation.

[Kinetic analysis of additive effect on desulfurization activity].

The additive effects of A12O3, Fe2O3 and MnCO3 on CaO sulfation kinetics were investigated by thermogravimetic analysis method and modified grain model. The activation energy (Ea) and the pre-exponential factor (k0) of surface reaction, the activation energy (Ep) and the pre-exponential factor (D0) of product layer diffusion reaction were calculated according to the model. Additions of MnCO3 can enhance the initial reaction rate, product layer diffusion and the final CaO conversion of sorbents, the effect mechanism of which is similar to that of Fe2O3. The method based isokinetic temperature Ts and activation energy can not estimate the contribution of additive to the sulfation reactivity, the rate constant of the surface reaction (k), and the effective diffusivity of reactant in the product layer (Ds) under certain experimental conditions can reflect the effect of additives on the activation. Unstoichiometric metal oxide may catalyze the surface reaction and promote the diffusivity of reactant in the product layer by the crystal defect and distinct diffusion of cation and anion. According to the mechanism and effect of additive on the sulfation, the effective temperature and the stoichiometric relation of reaction, it is possible to improve the utilization of sorbent by compounding more additives to the calcium-based sorbent.