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The cytological characteristics of major green-tide-forming green algae Ulva prolifera collected from Yellow Sea were studied through cutting segments, long time low temperature or dark treatments. After being dried in the shade and preserved at -20°C for 30 days, the U. prolifera was cultured at 4°C in sterilized seawater under 40 μmol photons m-2·s-1 light intensity for 120 days, results indicated that the plastid of U. prolifera continuously shrank with the extension of treatment, and most cells turned white and died, only a small amount of cells still contained a few of visible inclusions at the 120d of treatment. Then those samples were transferred to 20°C and 40 μmol photons m-2·s-1 condition for recovery cultivation, after about 10 days, some recovery cells were observed in the thallus, and those cells developed to young thallus gradually and released germ cells almost in the same time. After about 60 days of recovery cultivation, the newly-grown green thallus broke through the original dead thallus, and the germ cells also grew to new individual thallus. Before dark treatment, the U. prolifera cells were filled with plastid, contained visible starch grain and discernible cell outlines, while after 120 days of dark treatment, the plastid shrank and degraded together with the disappearance of cell inclusions, and the cell outlines also blurred, then those samples were transferred to optimal culture conditions at 20°C in 40 μmol photons m-2·s-1 light intensity, and 15 days later, newly-grown cells appeared on the almost dead thallus, these cells divided continuously and grew to young thallus, and those newly-grown thallus also generated active germ cells, which developed to new thallus that cytologically identical to the original thallus. Observation of chopped tissue of U. prolifera cultivated at 20°C, 40 μmol m-2·s-1 showed that the morphological upper part cells turned to germ cells first, those germ cells including gametophyte and sporophyte, which released later and grew to new individual thallus. These findings provided cytological evidences for how U. prolifera live through stress conditions such as low temperature, darkness, and also useful for understanding the mechanism of the occurrence of green tide.

Background Acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have a high relapse rate and poor prognosis. This study aims to explore the underlying mechanism of combining Gilteritinib with ATO at low concentration in the treatment of FLT3-ITD positive leukemias. Methods We used both in vitro and in vivo studies to investigate the effects of combination of Gilteritinib with ATO at low concentration on FLT3-ITD positive leukemias, together with the underlying molecular mechanisms of these processes. Results Combination of Gilteritinib with ATO showed synergistic effects on inhibiting proliferation, increasing apoptosis and attenuating invasive ability in FLT3-ITD-mutated cells and reducing tumor growth in nude mice. Results of western blot indicated that Gilteritinib increased a 160KD form of FLT3 protein on the surface of cell membrane. Detection of endoplasmic reticulum stress marker protein revealed that IRE1a and its downstream signal phosphorylated JNK were suppressed in Gilteritinib-treated FLT3-ITD positive cells. The downregulation of IRE1a induced by Gilteritinib was reversed with addition of ATO. Knockdown of IRE1a diminished the combinatorial effects of Gilteritinib plus ATO treatment and combination of tunicamycin (an endoplasmic reticulum pathway activator) with Gilteritinib achieved the similar effect as treatment with Gilteritinib plus ATO. Conclusions Thus, ATO at low concentration potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK signal pathway, targeting IRE1a to cooperate with Gilteritinib may serve as a new theoretical basis on FLT3-ITD mutant AML treatment.

Additional file 1: Figure S1 Analysis on FLT3 (160KD and 130KD) in ATO and Gilteritinib treated MV4-11 and MOLM13 cells. A-B, MV4-11 and MOLM13 cells were treated with ATO (0.5 µM) for 48 h and data of protein levels of FLT3 are shown as the mean ± SD. C, D, MV4-11 and MOLM13 cells were treated with Gilteritinib (2.5 nM) for 48 h and data of protein levels of FLT3 are shown as the mean ± SD. *P

Bangia fuscopurpurea is a farmed species in the ancient family Bangiales. It inhabits upper intertidal zones and suffers periodical desiccation and osmotic stress. The transcriptomic regulation under dehydration and hyposalinity was investigated. The differentially expressed genes (DEGs) accounted for 18.7% of the unigenes obtained by de novo transcriptome assembly (|log2fold-change| ≥ 1, FDR ≤ 0.001). Over 72% of the DEGs were downregulated under stress. The DEGs were predominantly enriched into the KEGG pathways “metabolic pathways,” “ribosome,” “biosynthesis of secondary metabolites,” “protein processing in endoplasmic reticulum,” and “oxidative phosphorylation.” The optimum photosynthetic efficiency (Fv/Fm) and photochemical quenching (qP) dropped significantly with 89% relative water loss and recovered rapidly after being rehydrated. Most DEGs regarding “photosynthesis” and “C3 carbon fixation” were upregulated in the dehydrated thalli, which may enable the thalli to gain photosynthetic recovery once being rehydrated. Fv/Fm and qP decreased significantly with 1 h of 90% freshwater treatment and then recovered to the control level 1 day later. With 6 h hyposaline treatment, expression of plasma membrane H+-ATPase genes was strongly and predominantly induced while the mRNA abundance of vacuolar, chloroplastic, and mitochondrial H+-ATPase genes decreased or showed no significant change. Some transporter, ion channel, and transmembrane protein genes together with the gene-encoding key enzymes involving in proline and heteroside metabolism were upregulated under hyposalinity. The results indicated that transmembrane exchange of ion and osmolytes was induced under hyposalinity to balance the osmotic fluctuation, which seemed to be triggered by plasma membrane H+-ATPases. These findings will facilitate elucidating the stress acclimation mechanism of B. fuscopurpurea.

Conchocelis cultivation is a crucial step in the industrial growth of Pyropia (laver). However, our knowledge of the seawater microbiology community in Pyropia seedling pools is limited. This study investigated the temporal dynamics in seedling pool microbiota before and after outbreaks of yellow spot disease in Pyropia yezoensis conchocelis. A total of 18 water samples were collected to assess seedling pool health status, followed by the sequencing of microbiota 16S ribosomal RNA (rRNA). Analysis of 16,760,224 16S rRNA gene sequences indicated that the core microbe group comprised 207 genera. The microbial diversity of samples gradually increased from May to July. The bacterial diversity of seawater samples from diseased P. yezoensis seedling pools was significantly higher than samples from healthy seedling pools. It is noteworthy that each pool group had a distinctive microbial community composition. The relative abundance of two dominant bacteria genera, Sediminicola and Roseivirga, increased over time in healthy seedling pools, peaking in August, while Vibrio remained at constantly low levels. However, the abundance of Vibrio and Polaribacter increased sharply in diseased P. yezoensis seedling pools and decreased after fresh seawater exchange. This indicates that these bacteria are probably associated with the filament disease. Many disease-associated bacteria are negatively related to the HCO3 − concentration in seawater and positively related to pH. Changes in bacteria and environmental factors reflect the characteristics of microbial community succession in seedling pools and therefore have potential to be used as biomarkers and environmental signals for Pyropia disease monitoring.

Summary The role of SRY-related high-mobility-group box (SOX) 12 in leukaemia progression and haematopoiesis remains elusive. This study aimed to examine the expression and function of SOX12 in acute myeloid leukaemia (AML) using human myeloid leukaemia samples and the acute myeloid cell line THP1. Mononuclear cells were isolated from the bone marrow of AML patients and healthy donors. SOX12 expression in haematopoietic cells was evaluated by reverse transcription polymerase chain reaction (RT-PCR). SOX12 short hairpin RNAs (shRNAs) were transduced into THP1 cells, and gene knockdown was confirmed by quantitative RT-PCR and Western blot analysis. SOX12 was preferentially expressed in CD34+ cells in AML patients. The THP1 cells transduced with SOX12 shRNAs exhibited significantly reduced SOX12 expression and cell proliferation. SOX12 knockdown had no effect on apoptosis, but it induced cell cycle arrest at G1 phase and reduced the number of colonies. The transduced THP1 and primary AML cells were reconstituted in non-obese diabetic-severe combined immunodeficient (NOD/SCID) mice, and their numbers were significantly reduced 6–12 weeks after transplantation. The mRNA and protein levels of β-catenin were significantly diminished following SOX12 knockdown, accompanied by a decrease in TCF/Wnt activity. SOX12 may be involved in leukaemia progression by regulating the expression of β-catenin and then interfering with TCF/Wnt pathway, which may be a target for AML.

Filamentous Bangia, which are distributed extensively throughout the world, have simple and similar morphological characteristics. Scientists can classify these organisms using molecular markers in combination with morphology. We successfully sequenced the complete nuclear ribosomal DNA, approximately 13 kb in length, from a marine Bangia population. We further analyzed the small subunit ribosomal DNA gene (nrSSU) and the internal transcribed spacer (ITS) sequence regions along with nine other marine, and two freshwater Bangia samples from China. Pairwise distances of the nrSSU and 5.8S ribosomal DNA gene sequences show the marine samples grouping together with low divergences (00.003; 0–0.006, respectively) from each other, but high divergences (0.123–0.126; 0.198, respectively) from freshwater samples. An exception is the marine sample collected from Weihai, which shows high divergence from both other marine samples (0.063–0.065; 0.129, respectively) and the freshwater samples (0.097; 0.120, respectively). A maximum likelihood phylogenetic tree based on a combined SSU-ITS dataset with maximum likelihood method shows the samples divided into three clades, with the two marine sample clades containing Bangia spp. from North America, Europe, Asia, and Australia; and one freshwater clade, containing Bangia atropurpurea from North America and China.

The ribosomal intergenic spacer (IGS) variation was compared for the nine main cultivated varieties of Pyropia yezoensis in China obtained from the Chinese National Pyropia Germplasm Repository. The full length of the IGS is 5984 bp including several sequence repeats and some complex structures. The sequence analysis of four partial IGS amplicons ranged from 3628 bp to 3776 bp; and the G+C content is 52.5%. Through similarity analysis and multiple sequence alignment of these partial IGS amplicons from the nine varieties, we have found 278 variable sites which account for approximately 7.5% of the whole IGS length. Both comparison of partial IGS sequences and phylogenetic analysis indicate high levels of genetic variation among different P. yezoensis cultivars in different areas of China. In comparison to the IGS of P. haitanensis, this study highlights the important function of classification of IGS in P. yezoensis. Therefore, the IGS sequence may be used to identify intraspecific variation in P. yezoensis.

High expression of the oncogene ecotropic viral integration site-1 (EVI-1) is an independent negative prognostic indicator of survival in leukemia patients. This study aimed to examine the effects of arsenic trioxide (ATO) on EVI-1 in acute myeloid leukemia (AML). Mononuclear cells were isolated from the bone marrow and peripheral blood of AML patients and healthy donors. EVI-1 expression in hematopoietic cells was evaluated by RT-qPCR and Western blot analysis. EVI-1 was highly expressed in both primary AML and leukemia cell lines (THP-1 and K562). ATO down-regulated EVI-1 mRNA in zebrafish in vivo as well as in primary leukemia cells and THP-1 and K562 cells in vitro. Additionally, ATO treatment induced apoptosis, down-regulated both EVI-1 mRNA and oncoprotein expression, increased the expression of pro-apoptosis proteins, and decreased the expression of anti-apoptotic proteins in leukemia cells in vitro. EVI-1 expression in leukemia cells (THP-1 and K562) transduced with EVI-1 siRNA was significantly reduced. Silencing EVI-1 had a significant effect on the activation of the JNK pathway and the induction of leukemia cell apoptosis. ATO may downregulate EVI-1 mRNA and oncoprotein levels and block the inhibitory effects of EVI-1 on the JNK pathway, which activates the JNK apoptotic pathway, thereby leading to the apoptosis of EVI-1 in AML patients.

FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) which occurs in approximately 30% of all AML patients still has a poor prognosis. This study aimed to examine the effect of decitabine (DAC) on FLT3-ITD positive AML. In our study, we found that expression of FLT3 and its downstream targets was decreased in FLT3-ITD mutant cell lines treated with DAC. DAC treatment could increase the percentage of apoptotic cells and CD11b positive cells tested by flow cytometry and upregulate the expression of cleaved caspase3, cleaved PARP, C/EBPa and PU.1 detected by western blot. To explore the effect of increased expression of PU.1 on FLT3 protein, we transiently transfected MOLM13 and MV4-11 cells with siRNA against PU.1 and a siRNA control. In both FLT3-ITD positive cells, the effect of DAC on downregulation of FLT3 was diminished in PU.1-konckdown MOLM13 and MV4-11 cells and there was a decrease of CD11b expression after PU.1 knockdown. Furthermore, the percentage of apoptotic cells was also decreased in PU.1-konckdown cells compared with siRNA control-expressing cells with the same dose of DAC. These findings indicated that DAC upregulated PU.1 to induce downregulation of FLT3 to trigger apoptosis. DAC was also found efficacious in mouse xenograft models of FLT3-ITD AML in our study. These findings may provide a novel theoretical basis for treatment of FLT3-ITD positive AML patients.

The complete nuclear ribosomal DNA (nrDNA) cistron sequence of Pyropia yezoensis has been sequenced, of which each unit is composed of the intergenic spacer (IGS), the small-subunit (SSU) ribosomal RNA (rRNA) gene, the internal transcribed spacer 1 (ITS1), the 5.8S rRNA gene, the internal transcribed spacer 2 (ITS2), and the large-subunit (LSU) rRNA gene. This cistron occurs in tandem repeats that can number in 100s to 1000s. Furthermore, in the analysis of the sequence data, we determined that introns were present in the small-subunit rRNA genes, for which the exon sequences (1834 bp) are almost identical. The intron numbers ranging from zero to two in the small-subunit rRNA genes are different between multiple individuals. However, the full length of the large-subunit rRNA genes is 4770 bp without any introns, and the 5.8S rRNA gene is 159 bp. Moreover, the 5′ and 3′ terminal sequences of the genic regions of the ribosomal cistron are extremely conservative even among various species in red alga. In addition, the range for ITS1 is 371–372 bp and for ITS2 is 532 to 535 bp. The IGS is 5984 bp in length and possesses upstream direct repeats, downstream repeats, and middle inverted repeats that make sequencing untoward. This is the first time that the complete nucleotide of the IGS region of P. yezoensis has been sequenced. The provision of the full length of nrDNA cistron will offer useful information to be widely utilized for identification, taxonomic relationships, and phylogenies in red algae.

The photosynthetic characteristics of a Pyropia haitanensis red mutant mutated from a wild-type strain using chemical mutagens were studied. The aim was to compare the differences in photosynthetic characteristics between the red mutant and the wild type, and then to analyse the possibility of the red mutant as breeding material. The results indicated that the cytoplasm thickness of the red mutant and the wild type were similar, whereas the cell wall of the red mutant was significantly thinner than that of the wild type. Additionally, the chlorophyll a extract absorption spectra of both strains exhibited no obvious difference, whereas the absorption peaks at 498, 545, and 565 nm (which belong to phycoerythrin, PE) in the phycobiliprotein extract absorption spectra of the red mutant were clearly higher than those of the wild type. The PE content per area of the red mutant thallus was significantly higher than that of the wild type, and the ratios of PE to phycocyanin (PC) and PE to chlorophyll a were significantly higher in the red mutant than in the wild type. The net photosynthetic oxygen evolution rates of the red mutant and wild type cultured under different light intensities demonstrated that the oxygen evolution rates of all samples decreased with increasing light intensities, whereas the oxygen evolution rate of the red mutant was higher than that of the wild type under the same light intensities. The light response curves also indicated that the light-saturated photosynthetic rates (P max), light saturation points (LSPs), and light compensation points (LCPs) of both strains decreased to different degrees with increasing light intensities and that the P max and LSP values of the red mutant were significantly higher than those of the wild type under identical light intensities. In contrast, there were no obvious differences in the respiration rate (R d) and in the LCP. The F v/F m values of both strains were similar before light treatment, whereas the F v/F m of the red mutants after culture under different light intensities (120 and 200 μmol photons m−2 s−1) for 3 days were significantly higher than those values of the wild type. Moreover, ∆F/F m′ also exhibited a similar variation. Based on these results, the high content of PE in the P. haitanensis red mutant causes a steady red phenotype, and the increase in the PE concentration and the decrease in the thickness of the thallus may enhance its photosynthetic physiological activity. Thus, the red mutant of P. haitanensis may provide good material for Pyropia breeding.

Carotenoid metabolism in red algae is not well understood. Geranylgeranyl diphosphate (GGPP), synthesized by GGPP synthase (GGPS), is a precursor for the biosynthesis of many biologically important metabolites, including carotenoids and chlorophylls. GGPSs have been functionally characterized in many organisms, but not in species of the primitive red algal order Bangiales. Here, we cloned and characterized the gene encoding GGPS (PuGGPS) in Pyropia umbilicalis (Bangiales). PuGGPS encodes a protein of 345 amino acids with an N-terminal transit peptide. The catalytic activity of PuGGPS for the production of GGPP was verified by a color complementation assay in Escherichia coli and subsequent high-performance liquid chromatography analysis. Homology modeling of PuGGPS showed that its tertiary structure resembles that of other known GGPSs and that this structure allows for the precise docking of the enzymatic product of PuGGPS, GGPP. When leafy thalli of P. umbilicalis were treated with norflurazon, an inhibitor of the key carotenoid metabolism enzyme phytoene desaturase, the expression of PuGGPS increased by twofold compared with that of the control in the first 2 h, suggesting a prompt response to metabolic perturbation. Prolonged norflurazon treatment failed to increase PuGGPS expression. Sequence analysis showed that PuGGPS shares seven conserved motifs with other previously identified GGPSs from different organisms, including two aspartate-rich GGPS signature motifs. Phylogenetic analysis also indicated that PuGGPS is a member of the type II GGPSs found in eubacteria and plants.

A molecular taxonomic study was undertaken for the first time of the bladed Bangiales of the mainland coast of China (Northwest Pacific) based on sequence data of 201 plastid rbcL and 148 nuclear 18S sequences of historical and contemporary specimens. The results revealed that only one genus of bladed Bangiales, Pyropia, was present along Chinese coast. Species delimitation was determined using two empirical methods: the Automatic Barcode Gap Discovery (ABGD) and General Mixed Yule Coalescence (GMYC) coupled with detection of monophyly in tree reconstruction. At least fourteen species of Pyropia were recovered. Six species were confirmed that had been recorded previously based on morphology (Py. suborbiculata, Py. yezoensis, Py. haitanensis, Py. katadae, Py. tenera and Py. acanthophora), three species were recorded from China for the first time (Py. kinositae, Py. pseudolinearis and Py. tanegashimensis), and five cryptic species that did not match any molecular sequences were also discovered. The phylogeny of the concatenated rbcL and 18S dataset resolved three singletons and four clades. Each clades has a strong trend towards occupying a biogeographic region, but they are not confined to them. A transoceanic and antitropical pattern of distribution was found for Pyropia at both the subgeneric and species level. This together with high biodiversity (ca. 30% of all known Pyropia species) indicates that the Northwest Pacific might act as a centre of origin for modern distribution of Pyropia since the early Cenozoic.

The characteristics of distribution of Pseudomonas aeruginosa in patients with agranulocytosis and fever in 12 hospitals in Shanghai from 2012 to 2014 were retrospectively analyzed. WHONET 5.6 software was used to analyze the results of drug sensitivity test. Data from different diseases, different sample sources, and drug sensitivity tests were statistically analyzed to investigate the clinical distribution characteristics and drug resistance of Pseudomonas aeruginosa in patients with agranulocytosis and fever in Shanghai, China. This study revealed that, among these 109 strains of P. aeruginosa, they were mainly found in patients with acute myelocytic leukemia (AML; 48 strains, 44.04%) and patients with acute lymphocytic leukemia (ALL; 36 strains, 33.03%). The specimen sources were mainly respiratory tract secretions (58 strains, 53.21%) and blood (21 strains, 19.26%). The P. aeruginosa isolates from neutropenic sepsis patients showed high sensitivity to the following antibiotics: piperacillin/tazobactam, cefepime, ciprofloxacin, ceftazidime, and amikacin with 91.1%, 89%, 89%, 87.9%, and 85.7% of isolates being sensitive, respectively. Furthermore, for P. aeruginosa isolates from the AML group of patients, the lowest antibiotic resistance rates were seen for ciprofloxacin (0%), cefoperazone/sulbactam (2.1%), and cefepime (7.1%), while for the ALL group the lowest antibiotic resistance rates were seen for piperacillin (2.8%), ceftazidime (2.8%), and cefepime (2.8%). Isolates from AML patients (21.3%) were significantly more likely to be piperacillin resistant than those from the ALL patients (2.8%). Therefore, P. aeruginosa infection is relatively common in patients with agranulocytosis and fever. The strains had a certain degree of resistance to commonly used antibiotics.

The metabolic pathway of 8-heptadecene in red algae was investigated. The results showed that the amounts of 8-heptadecene in the primitive bangiophycidean red algae Pyropia and Bangia were 30–50 % of the volatile compounds, much higher than that in the green alga Ulva pertusa, the brown alga Sargassum thunbergii and the florideophycidean red alga Gracilaria lemaneiformis. Studies on the metabolism of 8-heptadecene in Pyropia found that its enzymatic system has no significant catalytic activity on palmitic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid. However, the isolated enzymatic solution showed activity in the presence of eicosapentaenoic acid. This activity produced about four times the amount of 8-heptadecene compared with other substrates and the control, indicating the solution had a specific catalytic function for eicosapentaenoic acid. Furthermore, the enzyme solution was strongly inhibited by NaN3 but not by phenidone and phenanthroline suggesting that the enzyme is structurally related to heme protein. Thus, it is believed that a constant amount of 8-heptadecene is maintained in the primitive red alga Pyropia and the 8-heptadecene is a metabolite of eicosapentaenoic acid and may catalyzed by enzymes including a heme lipoxygenase-like enzyme.

The photosynthetic characteristics of thalli of cultured Pyropia yezoensis strains collected in January, February, and March in seaweed cultivation area of South China Yellow Sea were studied. Results showed that the maximum quantum efficiency (F v/F m) of all P. yezoensis thallus collected at different times was 0.65. The actual quantum efficiency (ΔF/F m′) of samples in January was the lowest of all samples, while the ΔF/F m′ of samples in March was significantly higher than those in January and February. The increase of temperature and photosynthetic pigments ratios of phycoerythrin and chlorophyll a (PE/Chla) and phycocyanin and chlorophyll a (PC/Chla) from January to March may be the important reasons for the increase in light use efficiency of thallus; although the thallus in March was significantly thicker than in January which may have reduced the light energy absorbed by photosynthetic pigments, the increase of relative high energy use efficiency also helped to maintain the photosynthetic oxygen evolution rate in March. The thicker thallus also reduced photodamage, and the thallus area was increased obviously in March, so the growth rate of thallus in March was over 35 % higher than that in February. Our research indicates that the photosynthetic characteristics of P. yezoensis strains thalli have a close relationship with their growth stage and environmental factors especially temperature, and those photosynthetic characteristics are also reflected in the growth rate of the thalli.

In this study, chlorophyll fluorescence parameters (∆F/F m′, F v/F m) and oxygen evolution of female vegetative tissues of Porphyra katadai var. hemiphylla in unisexual culture (FV) and in mixed culture with male vegetative tissues (FV-M) were followed at 5–20 °C, 10 and 80 μmol photons m−2 s−1. The formation of reproductive tissues was closely correlated with decreasing photosynthetic activities. At the same temperature the tissues cultured under 80 μmol photons m−2 s−1 showed a greater extent of maturation than those under 10 μmol photons m−2 s−1, and their decrease in photosynthesis was also larger. Under the same light intensity the extent of maturation increased with increasing temperature, and both cultures showed higher values of ∆F/F m′ and F v/F m at 10 and 15 °C, while their oxygen evolution became negative at 15–20 °C during the later period. Under the same culture condition the maturation of FV-M culture was relatively faster than that of FV culture, while their photosynthetic activity, especially ∆F/F m′, was lower.

Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi (previously called Porphyra yezoensis) is an economically important alga. The blades generated from conchospores are genetic chimeras, which are not suitable for genetic similarity analysis. In this study, two types of blades from a single filament of P. yezoensis sporophyte filament were obtained. One type, ConB, consisted of 40 blades that had germinated from conchospores. The other type, ArcB, consisted of 88 blades that had germinated from archeospores released from ConB. Both of them were analyzed by amplified fragment length polymorphism. The low genetic similarity levels for both conchospore-germinated and archeospore-germinated blades demonstrated that the conchcelis we used was cross-fertilized. Furthermore, a higher polymorphic loci ratio (98.6%) was detected in ArcB than in ConB (80.7%), and the average genetic similarity of ArcB (average 0.61) was lower than that of ConB (average 0.71). These differences indicated that genetic analysis using ArcB gives more accurate results.

Photosystem II photochemistry and phycobiliprotein (PBP) genes of red algaeKappaphycus alvarezii, raw material ofκ-carrageenan used in food and pharmaceutical industries, were analyzed in this study. Minimum saturating irradiance (Ik) of this algal species was less than 115 μmol m−2 s−1. Its actual PSII efficiency (yield II) increased when light intensity enhanced and decreased when light intensity reached 200 μmol m−2 s−1. Under dim light, yield II declined at first and then increased on the fourth day. Under high light, yield II retained a stable value. These results indicate thatK. alvareziiis a low-light-adapted species but possesses regulative mechanisms in response to both excessive and deficient light. Based on the PBP gene sequences,K. alvarezii, together with other red algae, assembled faster and showed a closer relationship with LL-Prochlorococcuscompared to HL-Prochlorococcus. Many amino acid loci in PBP sequences ofK. alvareziiwere conserved with those of LL-Prochlorococcus. However, loci conserved with HL-Prochlorococcusbut divergent with LL-Prochlorococcuswere also found. The diversities of PE and PC are proposed to have played some roles during the algal evolution and divergence of light adaption.

The formation of archeospores is characteristic of Porphyra yezoensis Ueda and is important for Porphyra aquaculture. Recently, it has been regarded as a valuable seed source for propagation of thalli in mariculture. Cell wall composition changes are associated with archeospore formation in P. yezoensis. Here, we report changes of cell walls of P. yezoensis during archeospore formation. The surfaces of vegetative cells that were originally smooth became rougher and more protuberant as archeosporangia were formed. Ultimately, the cell walls of archeosporangia ruptured, and archeospores were released from the torn cell walls that were left at distal margins of thalli. With changes in cell walls, both effective quantum yield and maximal quantum yield of the same regions in thalli gradually increased during the transformation of vegetative cells to archeospores, suggesting that the photosynthetic properties of the same regions in thalli gradually increased. Meanwhile, photosynthetic parameters for different sectors of thalli were determined, which included the proximal vegetative cells, archeosporangia, and newly released archeospores. The changes in photosynthetic properties of different sectors of thalli were in accordance with that of the same regions in thalli at different stages. In addition, the photosynthetic responses of archeosporangia to light showed higher saturating irradiance levels than those of vegetative cells. All these results suggest that archeosporangial cell walls were not degraded prior to release but were ruptured via bulging of the archeospore within the sporangium, and ultimately, archeospores were discharged. The accumulation of carbohydrates during archeospore formation in P. yezoensis might be required for the release of archeospores.

Photosynthetic characteristics of four Porphyra yezoensis Ueda [a taxonomic synonym of Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi] strains in conchocelis phase were investigated and compared with one wildtype of P. yezoensis and two strains of Porphyra haitanensis T. J. Chang et B. F. Zheng [a taxonomic synonym of Pyropia haitanensis (T. J. Chang et B. F. Zheng) N. Kikuchi et M. Miyata]. Results showed that experimental strains had higher contents of chl a and carotenoids, but a lower content of total phycobiliproteins than the wildtype. Meanwhile, photochemical efficiency of PSII was measured using pulse amplitude modulation (PAM) fluorometry technology. The value of PSII photosynthetic parameters of P. yezoensis strains were all higher than the wild strain, and the maximal quantum yields (Fv /Fm ), effective quantum yields Y(II), and relative photosynthetic electron transport rates (rETR) of P. haitanensis were higher than those of P. yezoensis. The present study verified the possibility of selective breeding of P. yezoensis using the filamentous sporophyte instead of the gametophytic thallus, the advantages being (i) nonrequirement of control of life cycle and (ii) direct and rapid cultivar improvement by artificial selection. We consider the method to be a promising technique for selective breeding of P. yezoensis cultivars.

Photosynthetic characteristics of four Porphyra yezoensis Ueda [a taxonomic synonym of Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi] strains in conchocelis phase were investigated and compared with one wildtype of P. yezoensis and two strains of Porphyra haitanensis T. J. Chang et B. F. Zheng [a taxonomic synonym of Pyropia haitanensis (T. J. Chang et B. F. Zheng) N. Kikuchi et M. Miyata]. Results showed that experimental strains had higher contents of chl a and carotenoids, but a lower content of total phycobiliproteins than the wildtype. Meanwhile, photochemical efficiency of PSII was measured using pulse amplitude modulation (PAM) fluorometry technology. The value of PSII photosynthetic parameters of P. yezoensis strains were all higher than the wild strain, and the maximal quantum yields (Fv /Fm ), effective quantum yields Y(II), and relative photosynthetic electron transport rates (rETR) of P. haitanensis were higher than those of P. yezoensis. The present study verified the possibility of selective breeding of P. yezoensis using the filamentous sporophyte instead of the gametophytic thallus, the advantages being (i) nonrequirement of control of life cycle and (ii) direct and rapid cultivar improvement by artificial selection. We consider the method to be a promising technique for selective breeding of P. yezoensis cultivars.

Background Acute myeloid leukemia (AML) 1-Evi-1 is a chimeric gene generated by the t (3; 21) (q26; q22) translocation, which leads into malignant transformation of hematopoietic stem cells by unclear mechanisms. This in vivo study aimed to establish a stable line of zebrafish expressing the human RUNX1-Evi-1 fusion gene under the control of a heat stress-inducible bidirectional promoter, and investigate its roles in hematopoiesis and hematologic malignancies. Methods We introduced human RUNX1-Evi-1 fusion gene into embryonic zebrafish through a heat-shock promoter to establish Tg(RE:HSE:EGFP) zebrafish. Two males and one female mosaic F0 zebrafish embryos (2.1 %) were identified as stable positive germline transgenic zebrafish. Results The population of immature myeloid cells and hematopoietic blast cells were accumulated in peripheral blood and single cell suspension from kidney of adult Tg(RE:HSE:EGFP) zebrafish. RUNX1-Evi-1 presented an intensive influence on hematopoietic regulatory factors. Consequently, primitive hematopoiesis was enhanced by upregulation of gata2 and scl, while erythropoiesis was downregulated due to the suppression of gata1. Early stage of myelopoiesis was flourishing with the high expression of pu.1, but it was inhibited along with the low expression of mpo. Microarray analysis demonstrated that RUNX1-Evi-1 not only upregulated proteasome, cell cycle, glycolysis/gluconeogenesis, tyrosine metabolism, drug metabolism, and PPAR pathway, but also suppressed transforming growth factor β, Jak-STAT, DNA replication, mismatch repair, p53 pathway, JNK signaling pathway, and nucleotide excision repair. Interestingly, histone deacetylase 4 was significantly up-regulated. Factors in cell proliferation were obviously suppressed after 3-day treatment with histone deacetylase inhibitor, valproic acid. Accordingly, higher proportion of G1 arrest and apoptosis were manifested by the propidium iodide staining. Conclusion RUNX1-Evi-1 may promote proliferation and apoptosis resistance of primitive hematopoietic cell, and inhibit the differentiation of myeloid cells with the synergy of different pathways and factors. VPA may be a promising choice in the molecular targeting therapy of RUNX1-Evi-1-related leukemia.

Bacterial strains capable of utilizing glyphosate as the sole carbon source were isolated from contaminated soil by the enrichment culture method and identified based on partial 16S rRNA gene sequence analysis. Pseudomonas spp. strains GA07, GA09 and GC04 demonstrated the best degradation capabilities towards glyphosate and were used for the laboratory experiments of glyphosate bioremediation. Inoculating glyphosate-treated soil samples with these three strains resulted in a 2-3 times higher rate of glyphosate removal than that in non-inoculated soil. The degradation kinetics was found to follow a first-order model with regression values greater than 0.96. Cell numbers of the introduced bacteria decreased from 4.4 × 10(6) CFU/g to 3.4-6.7 × 10(5) CFU/g dry soil within 18 days of inoculation. Due to the intense degradation of glyphosate, the total dehydrogenase activity of the soil microbial community increased by 21.2-25.6%. Analysis of glyphosate degradation products in cell-free extracts showed that glyphosate breakdown in strain GA09 was catalyzed both by C-P lyase and glyphosate oxidoreductase. Strains GA07 and GC04 degraded glyphosate only via glyphosate oxidoreductase, but no further metabolite was detected. These results highlight the potential of the isolated bacteria to be used in the bioremediation of GP-contaminated soils.

The levels of photosynthetic pigments and chlorophyll fluorescence of Porphyra yezoensis strains selected from high-light environments were investigated. Sutong and Sulian strains originated from the same high-light environment but were selected from different sites on the Yellow Sea coast of Jiangsu Province, China. In January (a low temperature period), the Sulian strain and the WT (a widely cultivated strain) had higher levels of chlorophyll a, phycoerythrin, phycocyanin, and allophycocyanin, and higher actual photochemical efficiency of PSII (ΔF/F m′) than the Sutong strain. This indicated that Sulian and the WT may have better adaptation to low temperature. In March (an optimal temperature period), Sutong had higher levels of photosynthetic pigments and higher ΔF/F m′ than the WT and Sulian strains. This suggested that Sutong had higher light use efficiency at optimal temperatures and that most energy absorbed by PSII was used for photosynthetic electron transport. The differing areas of origin of these strains may have resulted in these differences in temperature adaptation.

The formation of archeospores is characteristic of Porphyra yezoensis Ueda and is important for Porphyra aquaculture. Recently, it has been regarded as a valuable seed source for propagation of thalli in mariculture. Cell wall composition changes are associated with archeospore formation in P. yezoensis. Here, we report changes of cell walls of P. yezoensis during archeospore formation. The surfaces of vegetative cells that were originally smooth became rougher and more protuberant as archeosporangia were formed. Ultimately, the cell walls of archeosporangia ruptured, and archeospores were released from the torn cell walls that were left at distal margins of thalli. With changes in cell walls, both effective quantum yield and maximal quantum yield of the same regions in thalli gradually increased during the transformation of vegetative cells to archeospores, suggesting that the photosynthetic properties of the same regions in thalli gradually increased. Meanwhile, photosynthetic parameters for different sectors of thalli were determined, which included the proximal vegetative cells, archeosporangia, and newly released archeospores. The changes in photosynthetic properties of different sectors of thalli were in accordance with that of the same regions in thalli at different stages. In addition, the photosynthetic responses of archeosporangia to light showed higher saturating irradiance levels than those of vegetative cells. All these results suggest that archeosporangial cell walls were not degraded prior to release but were ruptured via bulging of the archeospore within the sporangium, and ultimately, archeospores were discharged. The accumulation of carbohydrates during archeospore formation in P. yezoensis might be required for the release of archeospores.

Exosomes are a family of bioactive vesicles and play important roles in antigen presentation. A recent phase I clinical trial with an exosome vaccine derived from colorectal cancer has shown minor clinical benefit. Exosomes derived from leukaemia cell lines have been little studied so, in the present study, the immunoprotective effect of exosomes secreted by NB4 cells, a human acute promyelocytic leukaemia cell line, was investigated. NB4-derived exosomes expressed the proteins retinoic acid receptor a and interstitial cell adhesion molecule 1 and contained heat shock protein 70, as demonstrated by transmission electron microscopy and Western blotting. Cytotoxicity assay demonstrated that cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) pulsed with exosomes were significantly more effective in killing target NB4 cells than CTLs induced by DCs alone. Exosome-based vaccines may be a promising means of prolonging disease-free survival in acute promyelocytic leukaemia patients after induction therapy.

In January and February 2010, heavy sea ice formed along the coast of the Bohai Sea and the northern Yellow Sea, China. Intertidal organisms were subjected to serious freezing stress. In this study, we investigated the freezing tolerance of the upper intertidal economic seaweed Porphyra yezoensis. The maximum photochemical efficiency of PS II (F v/F m) in undehydrated thalli remained high after 24 h at −2°C and that in dehydrated thalli decreased in a proportion to thallial water loss. F v/F m dropped sharply after 24 h at −20°C, regardless of absolute cellular water content (AWC). The F v/F m in frozen thalli recovered rapidly at 0–20°C. A wide range of water loss in the thalli enhanced their tolerance to freezing. F v/F m values in undehydrated thalli dropped sharply after 3 d at −2°C or 10 d at −20°C while those in dehydrated thalli (20–53% AWCs) remained at high levels after 9 d at −2°C or 30 d at −20°C. These results indicate that P. yezoensis has high freezing tolerance by means of dehydration during the ebb tide and rapid recovery of F v/F m from freezing. A strategy of P. yezoensis industry to avoid heavy loss during freezing season is discussed based on these findings.

Two strains, which are the free-living conchocelis of Porphyra yezoensis Ueda and Porphyra haitanensis T. J. Chang et B. F. Zheng, and four “interspecific hybridization” strains of these two species are investigated. The rbcL genes of 11 samples were amplified and sequenced, each of which were about 1,400 bp with a good specificity. The results of pair-wise distance matrix and multi-alignment showed that pair-wise distance were small while homologous index was large between strains Y-2066, Y-k2001, and Y-H001. These two indexes showed the same level as the above between strains H-2001, Y-hyC1, and Y-hyC2; however, the distances were larger between three former strains and three latter strains. Cluster trees showed the same trend. Fertile strains appeared after 2 years of culture of unfertile interspecific hybridization conchocelis and were separated from that based on different colors. Our finding that these fertile strains can bear offspring is important for understanding the interspecies hybridization of Porphyra. Molecular analysis of the fertile strains based on rbcL gene showed maternal inheritance. We inferred that somatic recombination was one of the reasons making interspecific hybridization strains fertile.

Pigment mutants were used as genetic markers to study the early development and morphogenesis of blades in four species of Porphyra. In Porphyra haitanensis, P. yezoensis, and P. oligospermatangia, the first two divisions are transverse during conchospore germination, yielding four cells arranged in a line. These species are representative of linear development pattern in Porphyra. Resulting in blades with color sectors vertically arranged. In P. katadai var. hemiphylla, the first division is transverse and the upper cell divides vertically forming two side-by-side cells, and its blades are derived mostly from the upper cell showing a bilateral development pattern with two lateral parts of different colors. In this type of germination, most or the entire blade is derived from the upper cells. Some fronds of P. katadai var. hemiphylla developed in linear pattern. In addition, 9.3% of the conchospore germlings of linear development were produced at 10°C, 15.3% at 15°C, and 38.0% at 20°C for conchospore germlings of P. katadai var. hemiphylla. More linear development occurred at higher temperatures. The results revealed general trends of early developmental patterns and morphogenesis of blades within the genus of Porphyra. Developmental patterns and morphogenesis of blades are under the influence of temperatures.

Bangia fuscopurpurea (Rhodophyta) was cultivated in Putian (Fujian province, China). The characteristics of the life history concerned with cultivation were investigated and the cultivation procedure was presented. The gametophytic phase (thallus) and the sporophytic phase (conchocelis) occurred alternately in the life history of B. fuscopurpurea. Young thalli produced archeospores, and the number depended on the environmental factors. Temperature affected the number of archeospore release and percent of germination, and photo flux density (PFD) mainly affected the time of spore release and germination. Thalli matured from December to February and developed into the conchocelis phase through sexual reproduction. The conchocelis grown in shells had three developmental stages: vegetative conchocelis, conchosporangiall formation and conchospore formation. Pit-connections were present in the first 2 stages but absent after conchospore formation. Vegetative conchocelis and conchosporangial. branches can transform into each other. However, conchospores only developed into the gametophytic phase. Cultivation of B. fuscopurpurea was based on characterization of the life history, consisting of 3 steps: zygotospores collection, indoor cultivation of conchocelis and outdoor cultivation of thalli. Young thalli that developed from conchospores produced numerous archeospores before December. Over 90% of the crop was from the development of archeospores. The results indicated that conchosporelings were a good source of archeospores, and the development of the large quantity of archeospores acted as a more prevailing means to increase the population size. (C) 2008 Elsevier B.V. All rights reserved.

The color mutations in Bangiaceae were investigated by treating the blades, conchocelis and conchospores phase of Bangia sp., Porphyra yezoensis, and P. haitanensis sampled in China with mutagen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). A high percentage of mutation in different expression characteristics in all three phases were shown within optimum mutagen concentrations. Among mutagenized blades, mutations occurred on single cells, which is a direct outcome of mutation of haploid cells. The mutation of mutagenized conchocelis resulted in a two-step process: low-level expression in conchocelis phase, and high-level expression in progeny, explaining that mutation took place in diploid cells. The mutations of conchospores were expressed immediately at germination of spores, indicating a change in ploidy. This paper reports the process of meiosis and its effect on frond development, and the relation between color mutations and morphological characteristics expressed by mutations in Bangiaceae.

Nuclear divisions of carpospores, conchocelis and conchospores of Porphyra yezoensis, P. haitanensis, P. katadai var. hemiphylla and P. oligospermatangia from China were investigated. The observations showed diploid chromosome numbers of 2n = 6 for P. yezoensis and P. oligospermatangia, and 2n = 10 for P. haitanensis and P. katadai var. hemiphylla. For all four species, somatic pairing of chromosome sets was observed in late prophase. Sister chromosomes separated at anaphase as mitosis took place in carpospores, conchocelis filamentous cells, conchosporangial branch cells and sporangial cells (conchospore formation). Chromosome configurations of tetrad and ring-shaped in conchospore germination were observed, demonstrating the occurrence of meiosis. The characteristics of diploid nuclear division in 2n = 6 species are the same as those of 2n = 10 species. The influence of somatic pairing on nuclear division of diploid cells in Porphyra was discussed.

Background The mechanism behind poor survival of acute myeloid leukemia (AML) patients with 1-barabinofuranosylcytosine (Ara-C) based treatment remains unclear. This study aimed to assess the pharmacogenomic effects of Ara-C metabolic pathway in patients with AML. Methods The genotypes of 19 single nucleotide polymorphisms (SNPs) of DCK, CDA and SLC29A1from 100 AML patients treated with Ara-C were examined. All the SNPs were screened with ligase detection reaction assay. The transcription analysis of genes was examined by quantitative real time polymerase chain reaction. The association between clinical outcome and gene variants was evaluated by Kaplan-Meier method. Results Genotypes of rs9394992 and rs324148 for SLC29A1 in remission patients were significantly different from those in relapsed ones. Post-induction overall survival (OS) significantly decreased in patients with the CC genotype of rs324148 compared with CT and TT genotypes (hazard ratio [HR] = 2.997 [95% confidence interval (CI): 1.71-5.27]). As compared with CT and TT genotype, patients with the CC genotype of rs9394992 had longer survival time (HR = 0.25 [95% CI: 0.075-0.81]; HR = 0.43 [95% CI: 0.24-0.78]) and longer disease-free survival (DFS) (HR = 0.52 [95% CI: 0.29-0.93]; HR = 0.15 [95% CI: 0.05-0.47]) as well As compared with CT and TT genotype, patients with the CC genotype of rs324148 had shorter DFS (HR = 3.18 [95% CI: 1.76-5.76]). Additionally, patients with adverse karyotypes had shorter DFS (HR = 0.17 [95% CI: 0.05-0.54]) and OS (HR = 0.18 [95% CI: 0.05-0.68]). Conclusions AML patients with low activity of SLC29A1 genotype have shorter DFS and OS in Ara-C based therapy. Genotypes of rs9394992 and rs324148 may be independent prognostic predictors for the survival of AML patients. Electronic supplementary material The online version of this article (doi:10.1186/s13046-014-0090-9) contains supplementary material, which is available to authorized users.

Introduction Acute myeloid leukemia (AML) is a malignant clonal hematopoietic stem cell disease. Ecotropic viral integration site-1(EVI-1) has been recognized as one of the most dominant oncogenes associated with murine and human myeloid leukemia. EVI-1 harbors several hallmark functions that are normally associated with leukemogenesis. Overexpression EVI-1 upregulates the transcription of the transcription factor gene GATA-2, which plays a critical role in the maintenance of hematopoietic stem cells.EVI-1 also binds to the transcription factors GATA-1,PU.1,RUNX-1,SCL and LMO2 thereby inhibiting their activity and blocking the differentiation of hematopoietic progenitors. Arsenic trioxide (ATO), which was used as a traditional Chinese medicine, has shown excellent therapeutic efficiency for acutepromyelocyticleukemia. A previous study has demonstrated that ATO targets EVI-1 protein to induce apoptosis . However, the molecular mechanisms underlying this regulation of AML cells by ATO have not been fully elucidated. We aim to expand our understanding of the cellular regulation and effect of ATO on EVI-1 and several related transcription factors (such as GATA1, GATA2, RUNX-1, LMO2, PU-1) in human acute monocytic leukemia THP-1 cells. Methods The endogenous expression of EVI-1 is higher in THP-1 cells, which was confirmed through gene analysis sequencing and comparison with Genbank.THP-1 cells were treated with various concentrations of ATO( 0,1,3,5¦ÌM) for 24h, 48h and 72h. Expressions of EVI-1,and related transcription factor genes(GATA-2 ,GATA-1, RUNX-1,MPO,LMO,PU.1,SCL2) were determined by qRT-PCR. Results Compared to controls, THP-1 cells with high expression of EVI-1 gene were selected to confirm that overexpression of EVI-1 can promote the expression of GATA-2 , and reduce the level of GATA-1, RUNX-1, MPO, LMO, PU.1, SCL2 simultaneously in vitro(Fig.1).To determine whether ATO is able to directly regulate EVI-1 and related transcription factor genes expression in THP-1 cells, we examined their mRNA expression by qRT-PCR after treatment with different concentrations of ATO. We found that ATO has the ability to down regulate EVI-1 gene in a dose-dependent and time-dependent manner( Fig.2a).Moreover, GATA-2 gene expression decreased when THP-1 cells were treated with ATO(Fig.2b). We examined the related transcription factors expression and found that ATO suppressed the expression levels of PU.1, RUNX-1, SCL and LMO2 (Fig.2c, 2d, 2e) in THP-1 cells. Interestingly, exposure to increasing concentrations of ATO for increasing lengths of time was associated with gradual promotion in the expression of GATA-1 mRNA( Fig 2f). Summary We verified that the endogenous expression of EVI-1 is higher in THP-1 cells, which confirmed THP-1 cells can be a vitro model to investigate EVI-1 gene functions. Meanwhile, related transcription factor gene GATA-2, which is regarded as EVI-1 regulatory element, is upregulated in THP-1 cells. Moreover, GATA-1, which is essential for erythroid differentiation, and other related transcription factor genes (PU.1, RUNX-1, SCL and LMO2) decreased in THP-1 cells. ATO dose-and time-dependently decreased expressions of EVI-1 and GATA-2 gene and regulated those related transcription factors in EVI-1-overexpressing cells compared with control cells. Disclosure: No relevant conflicts of interest to declare. Disclosures Lang: National Natural Science Fundation of China (no.81470312),: Research Funding; Foundation of Shanghai Committee of Science and Technology (no. 14411950704): Research Funding. Chen:National Natural Science Fundation of China (no.81470312): Research Funding; Foundation of Shanghai Committee of Science and Technology (no. 14411950704): Research Funding. Zhu:Foundation of Shanghai Committee of Science and Technology (no. 14411950704): Research Funding; National Natural Science Fundation of China (no.81470312): Research Funding. Zhong:National Natural Science Fundation of China (no.81470312): Research Funding; Foundation of Shanghai Committee of Science and Technology (no. 14411950704): Research Funding.

Ketanserin, a hypotensive drug with 5-HT2 receptor antagonism, when administered by topical infusion of a 0.25% w/v solution by corneal and scleral applications, was found to lower intraocular pressure with four times more activity than its metabolite, ketanserinol. Drug and metabolite were measured periodically in the corneal epithelium, corneal stroma/endothelium, aqueous humor, iris/ciliary body, conjunctiva, sclera and lens during the infusion period (0-120 min) and the postinfusion period (120-240 min) using a fluorometric reversed-phase HPLC assay developed and verified for the research. The infusion results showed that drug entered the eye by both the corneal and scleral routes. Lateral diffusion occurred between the conjunctiva and corneal epithelium. Drug and metabolite were also detected in the untreated fellow eyes, suggesting contralateral systemic redistribution. In vitro metabolism was studied and found to occur in the corneal epithelium, iris/ciliary body and bulbar and palpebral conjunctiva but not in the corneal stroma/endothelium, aqueous humor and sclera. From noncompartmental analysis, zero-order infusion rate constants, first-order absorption constants, mean residence time, volumes of distribution at steady state (Vss) and clearance (Cle) were obtained using equations specific to the topical infusion method. Vss and Cle of aqueous humor (0.972 ml and 13.55 microl/min) were greater than aqueous humor volume (0.311 ml) and turnover rate (4.7 microl/min).

The aim of this study was to evaluate the difference in pharmacokinetics and pharmacodynamics between extended-release (ER) fluvastatin tablet and its immediate-release (IR) capsule in Chinese healthy subjects. This was an open-label, single/multiple-dose, two-period, two-treatment, crossover, randomized trial with a minimum washout period of 7 days. Twenty healthy male adult subjects were given fluvastatin ER tablet 80 mg QD by oral administration or fluvastatin IR capsule 40 mg BID for seven days. Blood samples were collected up to 24 hours after dosing on day 1 and day 7. Serum concentrations of fluvastatin were determined by LC-MS/MS. For fluvastatin ER tablet 80 mg QD, 𝐶 m a x was 61.0 ± 39.0 and 63.9 ± 29.7 ng/mL, and A U C 0 − 2 4 h was 242 ± 156 and 253 ± 91.1 ng·h/mL on day 1 and 7, respectively. For fluvastatin IR capsule 40 mg BID, 𝐶 m a x was 283 ± 271 and 382 ± 255 ng/mL, and A U C 0 − 2 4 h was 720 ± 776 and 917 ± 994 ng·h/mL on day 1 and day 7, respectively. The relative bioavailability of fluvastatin ER tablet 80 mg QD to fluvastatin IR capsule 40 mg BID is (45.3 ± 23.9)% and (43.3 ± 24.1)% on day 1 and day 7, respectively. 𝑇 m a x for fluvastatin ER tablet was 2.50 and 2.60 h and for capsule was 0.78 and 0.88 h on day 1 and day 7, respectively. In the first period, compared to baseline, cholesterol decreased 15.3% in fluvastatin ER tablet 80 mg QD and 16.9% in fluvastatin IR capsule 40 mg BID. Triglyceride decreased 3.7% in fluvastatin ER tablet 80 mg QD and 19.1% in fluvastatin IR capsule 40 mg BID. The difference has no statistical significance at 𝑃 > 0 . 0 5 in reduction percent of cholesterol and triglyceride between the two groups. No adverse events were recorded. The results indicated that 𝐶 m a x of fluvastatin ER tablet is reduced and 𝑇 m a x is prolonged compared with IR capsule. There is no accumulation for ER formulation after multiple doses.

Background Red algae are primitive photosynthetic eukaryotes, whose spores are ideal subjects for studies of photosynthesis and development. Although the development of red alga spores has received considerable research attention, few studies have focused on the detailed morphological and photosynthetic changes that occur during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi) Papenfuss (Gracilariales, Rhodophyta). Herein, we documented these changes in this species of red algae. Results In the tetraspores, we observed two types of division, cruciate and zonate, and both could develop into multicellular bodies (disks). During the first 84 hours, tetraspores divided several times, but the diameter of the disks changed very little; thereafter, the diameter increased significantly. Scanning electron microscopy observations and analysis of histological sections revealed that the natural shape of the disk remains tapered over time, and the erect frond grows from the central protrusion of the disk. Cultivation of tissue from excised disks demonstrated that the central protrusion of the disk is essential for initiation of the erect frond. Photosynthetic (i.e., PSII) activities were measured using chlorophyll fluorescence analysis. The results indicated that freshly released tetraspores retained limited PSII photosynthetic capabilities; when the tetraspores attached to a substrate, those capabilities increased significantly. In the disk, the PSII activity of both marginal and central cells was similar, although some degree of morphological polarity was present; the PSII photosynthetic capabilities in young germling exhibited an apico-basal gradient. Conclusions Attachment of tetraspores to a substrate significantly enhanced their PSII photosynthetic capabilities, and triggered further development. The central protrusion of the disk is the growth point, may have transfer of nutritive material with the marginal cells. Within the young germling, the hetero-distribution of PSII photosynthetic capabilities might be due to the differences in cell functions.

The co-existence of de novo myelodysplastic syndrome (MDS) and non-Hodgkin lymphoma (NHL) prior to therapy is an extremely unusual finding. We report here a case of co-existent de novo MDS-refractory cytopenia with multilineage dysplasia and T-cell NHL, including clinical features, histopathological findings, molecular assessment, treatment course and outcomes. Other cases from the literature showing co-existence of both disorders are also reviewed; to date 19 similar cases have been reported. Among all cases (including the present patient), eight cases were diagnosed with de novo MDS and NHL simultaneously, which were considered to be true coincidences. The mechanisms responsible for the appearance of co-existence have not yet been ascertained, however in the present case a common chromosomal abnormality (20q deletion) was found in bone marrow and lymph node preparations. We conclude, therefore, that the co-existent de novo MDS and T-cell NHL seen in the present case may have a common origin.