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Background Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. Methods Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. Results The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. Conclusions The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Few studies have reported the roles of the complement system in concomitant idiopathic membranous nephropathy and IgA nephropathy (IMN-IgAN). Complement factor B (CFB) is a crucial factor that involved in the alternative complement pathway. We aimed to evaluate the association between disease activity (eGFR, anti-PLA2R antibody levels and 24 h urinary protein excretion), progression and serum CFB levels of IMN-IgAN patients. In total, 39 IMN-IgAN patients (median follow-up, 46.6 months), 99 IMN patients and 92 IgAN patients participated in this study. The disease progression event was defined as end-stage renal disease (ESRD) or a 30% decline in estimated glomerular filtration rate (eGFR). The serum CFB concentration was measured by enzyme-linked immunosorbent assay. Serum CFB levels were lower in IMN-IgAN patients than in patients with IgAN only (P

To find the risk of time thresholds of PROM for infectious diseases of term neonates. A multi-center prospective cohort study including pregnancies with PROM at term with a single fetus were conducted. Time thresholds of the duration from PROM to delivery were examined in 2-h increments to assess the rates of infectious neonatal diseases. 7019 pregnancies were included in the study. Neonatal pneumonia and sepsis were most frequent infectious diseases in neonates born from mother with PROM at term. Rates of early-onset pneumonia varied significantly when comparing length of time of PROM greater than 16 h vs. less than 16 h (for EOP in 3 days of life, adjusted OR 1.864, 95% CI 1.159 ~ 2.997, p = 0.010; for EOP in 7 days of life, adjusted OR 1.704, 95% CI 1.104 ~ 2.628, p = 0.016). Neonates born from mother of whom the length of time from PROM to delivery ≥ 16 h were at a higher risk of acquiring EOP.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test–retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society–Unified Parkinson's Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

A series of nickel complexes {4a: [(2,6-iPr2C6H3)N=CHC16H12O]Ni(Me)(Py), 4b: [(2,6-iPr2C6H2OCH3)N=CHC16H12O]-Ni(Me)(Py), 4c: [(2,6-iPr2C6H2Cl)N=CHC16H12O]Ni(Me)(Py), and 4d: [(2,6-iPr2C6H2CF3)N=CHC16H12O]Ni(Me)(Py)} based on β-ketiminato ligands bearing various electron-donating or electron-withdrawing substituents on the para-position of the aniline group were synthesized and unambiguously characterized. The X-ray crystallographic analysis showed that complexes 4b and 4d adopted a near-square-planar geometry, and the anilines bearing a para-OMe or −CF3 group were found to situate on the axial position of the metal center. All complexes exhibited high activities up to 1.25 × 107–1.35 × 107 gPNB·molNi−1·h−1 toward norbornene (NBE) addition polymerization (conversion > 91.2% in 2 min) under low loading of B(C6F5)3 (B/Ni = 3) at 30 °C, affording polymers with high molecular weight up to 2.54 × 106–3.18 × 106. Different levels of decrease in catalytic activities could be observed for all catalysts as the reaction temperature increased; 4d bearing a strong electron-withdrawing −CF3 group showed the highest activity at 70 °C, while others exhibited notable decrease in catalytic activity with the raise in reaction temperature. Complexes 4a–4d showed remarkable tolerance to polar groups and could efficiently promote the copolymerization of NBE with its polar derivatives, including NBE bearing small acetate and hydroxyl group, as well as bulky oligomers, yielding copolymers with high functional NBE incorporations. Novel NBE copolymers with high functional comonomer incorporations and improved solubility were obtained in high yields.

microRNAs regulate diverse biological processes such as development and aging by promoting degradation or inhibiting translation of their target mRNAs. In this study, we have found that the miR-58 family microRNAs regulate lifespan in C. elegans. Intriguingly, members of the miR-58 family affect lifespan differently, sometimes in opposite directions, and have complex genetic interactions. The abundances of the miR-58 family miRNAs are up-regulated in the long-lived daf-2 mutant in a daf-16-dependent manner, indicating that these miRNAs are effectors of insulin signaling in C. elegans. We also found that miR-58 is regulated by insulin signaling and partially required for the lifespan extension mediated by reduced insulin signaling, germline ablation, dietary restriction, and mild mitochondrial dysfunction. We further identified the daf-21, ins-1, and isw-1 mRNAs as endogenous targets of miR-58. Our study shows that miRNAs function in multiple lifespan extension mechanisms, and that the seed sequence is not the dominant factor defining the role of a miRNA in lifespan regulation.

For many years, cerium-aluminum systems have been extensively studied because of their unusual magnetic behavior. As the atomic radii of cerium and aluminum differ greatly from each other, a solid solution is not obtained because of the Hume-Rothery rule. Therefore, intermetallic compounds are usually studied, and structural stability is crucial for further discussion of their physical properties. The present article reports on high-energy ball milling of the intermetallic compound Ce3Al at room temperature. It has been found that non-equilibrium supersaturated Ce solid solution was formed during the milling. The solubility of aluminum was estimated as 5 to 13 at. pct from the peak shifts of the X-ray diffraction pattern. The structural changes in the initial stages of the milling were also studied.

Background Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery. Objective In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods. Methods MMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel. Results Immediately following the 50 min incubation, both MMC solutions exhibited approximately 5–7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points. Conclusion We recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.

Cancer patients with predominantly hepatic metastases have poor outcomes and limited options. Hepatic arterial infusion (HAI) of a therapeutic agent may be an appropriate option for producing increased drug concentrations at the tumor sites while reducing systemic adverse effects in normal tissues.Patients with predominantly hepatic metastases (n = 48) were placed in 6 groups according to nanoparticle albumin-bound paclitaxel (nab-paclitaxel) dose level using a 3 + 3 design plus dose expansion for responsive tumor types. We evaluated the toxicity, antitumor activity, and pharmacokinetics of nab-paclitaxel delivered via HAI.Thirty-eight and ten patients underwent HAI over 1 and 4 h, respectively, at doses of up to 300 mg/m(2). The treatment was safe and exhibited antitumor activity. Pharmacokinetic analyses revealed that HAI of nab-paclitaxel over 4 h resulted in markedly lower peak drug concentrations (C max) and longer times to peak concentration (T max) than that over 1 h. The self-control pharmacokinetic studies showed that HAI of nab-paclitaxel led to much lower C max and areas under the curve (AUC), compared with intravenous infusion.HAI of nab-paclitaxel at up to 300 mg/m(2) over 4 h was well tolerated. Pharmacokinetic evaluation of C max, T max, and AUC implied that 4-h HAI enhanced hepatic extraction of nab-paclitaxel. Further preclinical and clinical studies are required to develop reliable methods of evaluation of hepatic extraction (clinicaltrials.gov registration number NCT00732836, first registered on August 8, 2008, and last updated on October 27, 2014).

Background Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies. Methods miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization. PC cell line (PC3 cell) was transfected with miR-193a-5p mimic or its inhibitor, and then cell apoptosis and the expression of its downstream genes Bach2 and HO-1 were detected by TUNEL staining and Western blotting. Luciferase reporter assay was used to detect the effect of miR-193a-5p and Bach2 on HO-1 expression. Xenograft animal model was used to test the effect of miR-193a-5p and docetaxel on PC3 xenograft growth. Results miR-193a-5p was upregulated in PC tissues and PC cell lines, with significant suppression of PC3 cell apoptosis induced by oxidative stress. Mechanistically, miR-193a-5p suppressed the expression of Bach2, a repressor of the HO-1 gene, by directly targeting the Bach2 mRNA 3′-UTR. Docetaxel treatment modestly decreased Bach2 expression and increased HO-1 level in PC3 cells, whereas a modest increase of HO-1 facilitated docetaxel-induced apoptosis. Notably, docetaxel-induced miR-193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis, as evidenced by the increased Bcl-2 and decreased Bax expression. Accordingly, silencing of miR-193a-5p enhanced sensitization of PC3 cells to docetaxel-induced apoptosis. Finally, depletion of miR-193a-5p significantly reduced PC xenograft growth in vivo. Conclusions Silencing of miR-193a-5p or blockade of the miR-193a-5p-Bach2-HO-1 pathway may be a novel therapeutic approach for castration-resistant PC. Electronic supplementary material The online version of this article (10.1186/s13046-017-0649-3) contains supplementary material, which is available to authorized users.

The Burmese roofed turtle (Batagur trivittata) is endemic to Myanmar, but was believed to be extinct until rediscovered in 2002. In the present study, it’s complete mitochondrial genome was reconstructed from whole-genome Illumina sequencing data. The circular genome is 16,463 bp in length, and harbors 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs) and one control region (D-loop). The putative control region (947 bp) is located between tRNA-Phe and tRNA-Pro, with an A + T content of 64.9 %. The base composition of the genome is A (33.6 %), C (28.6 %), G (13.3 %) and T (24.5 %) with an overall GC content of 41.9 %. Phylogenetic analysis suggests that B. trivittata is closely related to its confamilial counterparts than to the other taxa.

A new dinuclear Ca(II) complex, {[Ca(bpy)(H2O)4]2(μ-1,5-NDS)}·(1,5-NDS) (1,5-NDS = 1,5-naphthalenedisulfonate bpy = 2,2′-bipyridine) has been successfully synthesized in water:ethanol (1:5) medium, and was characterized by elemental analysis, IR and thermal analysis. Structurally characterized with the aid of X-ray single-crystal diffraction analysis, which revealed that the complex crystallizes in the triclinic system with the P-1 space group, and the complex molecules exhibit a novel one-dimensional supramolecular chain structure via hydrogen bonding interactions. The antitumor activity of 1,5-naphthalenedisulfonic acid sodium ligand and the dinuclear Ca(II) complex against human hepatoma SMMC-7721 cell line and human lung adenocarcinoma A549 cell line reveals that the Ca(II) complex is more resistive to this cell line as compared to 1,5-naphthalenedisulfonic acid sodium ligand.

With the development of cloud computing, more and more data-intensive workflows have been deployed on virtualized datacenters. As a result, the energy spent on massive data accessing grows rapidly. In this paper, an energy aware scheduling algorithm is proposed, which introduces a novel heuristic called Minimal Data-Accessing Energy Path for scheduling data-intensive workflows aiming to reduce the energy consumption of intensive data accessing. Extensive experiments based on both synthetical and real workloads are conducted to investigate the effectiveness and performance of the proposed scheduling approach. The experimental results show that the proposed heuristic scheduling can significantly reduce the energy consumption of storing/retrieving intermediate data generated during the execution of data intensive workflow. In addition, it exhibits better robustness than existing algorithms when cloud systems are in presence of I/O intensive workloads.

To observe the clinical efficacy and the change of airway responsiveness to Chinese medicine (CM) in treating cough variant asthma (CVA).Ninety-four patients who had confirmed the diagnosis of CVA were selected and randomly assigned to the treatment group and the control group by the blocked randomization method. The ratio of the two groups was 2:1. The treatment group had 63 patients that were treated by CM, lost in 10 cases, 53 patients had finished the trial. The control group had 31 patients that were treated by montelukast tablets and theophylline, lost in 5 cases, 26 patients had finished the trial, two weeks as one therapeutic course. The syndrome efficacy, cough efficacy, symptom score and the airway responsiveness between two groups were observed.The comparison of the syndrome efficacy: the total effective rate of the treatment group was 90.57% and the control group was 76.92%, and the two groups were significantly different (P0.05). The comparison of the cough efficacy: the total effective rate of the treatment group was 98.11% and the control group was 80.77%, and the two groups were also significantly different (P0.05). Syndrome scoring and cough scoring were all significantly lowered, but the airway responsiveness was not significantly lowered.The treatment of CM could ease the cough, improve the syndrome, and shows obvious advantages compared with the control group, which is worthy of extensive clinical application.

In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

Optogenetic approaches allow the manipulation of neuronal activity patterns in space and time by light, particularly in small animals such as zebrafish. However, most techniques cannot control neuronal activity independently at different locations. Here we describe equipment and provide a protocol for single-photon patterned optical stimulation of neurons using a digital micromirror device (DMD). This method can create arbitrary spatiotemporal light patterns with spatial and temporal resolutions in the micrometer and submillisecond range, respectively. Different options to integrate a DMD into a multiphoton microscope are presented and compared. We also describe an ex vivo preparation of the adult zebrafish head that greatly facilitates optogenetic and other experiments. After assembly, the initial alignment takes about one day and the zebrafish preparation takes

Plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. The present study was undertaken to examine the effects on pulmonary fibrosis of silencing PAI-1 expression with small interfering RNA (siRNA) and to assess the possible underlying mechanisms. Male Wistar rats were subjected to intratracheal injection of bleomycin (BLM, 5 mg/kg, 0.2 mL) to induce pulmonary fibrosis. Histopathological changes of lung tissue were examined with HE or Masson's trichrome staining. The expression levels of α-smooth muscle actin (α-SMA), collagen type-I and type-III, caspase-3, as well as p-ERK1/2 and PI3K/Akt in the lung tissue were evaluated using imunohistochemistry and Western blot analyses. The fibroblasts isolated from BLM-induced fibrotic lung tissue were cultured and transfected with pcDNA-PAI-1 or PAI-1siRNA. The expression level of PAI-1 in the fibroblasts was measured using real time RT-PCR and Western blot analysis. The fibroblast proliferation was evaluated using MTT assay. Intratracheal injection of PAI-1-siRNA (7.5 nmoL/0.2 mL) significantly alleviated alveolitis and collagen deposition, reduced the expression of PAI-1, α-SMA, collagen type-I and collagen type-III, and increased the expression of caspase-3 in BLM-induced fibrotic lung tissue. In consistence with the in vivo results, the proliferation of the cultured fibroblasts from BLM-induced fibrotic lung tissue was inhibited by transfection with PAI-1-siRNA, and accelerated by overexpression of PAI-1 by transfection with pcDNA-PAI-1. The expression of caspase-3 was increased as a result of PAI-1 siRNA transfection, and decreased after transfection with pcDNA-PAI-1. In addition, the levels of p-ERK1/2 and PI3K/Akt in the fibrogenic lung tissue were reduced after treatment with PAI-1siRNA. The data demonstrate that PAI-1 siRNA inhibits alveolitis and pulmonary fibrosis in BLM-treated rats via inhibiting the proliferation and promoting the apoptosis of fibroblasts. Suppression ERK and AKT signalling pathways might have at least partly contributed to this process. Targeting PAI-1 is a promising therapeutic strategy for pulmonary fibrosis.

Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes. Optogenetic stimulation in the zebrafish olfactory bulb and downstream read out of activity in the homologue of olfactory cortex demonstrate how temporal filtering can extract specific components of neuronal codes. Neurons in the olfactory bulb of zebrafish and other species respond to odours with complex firing that contains both oscillatory and non-oscillatory components, but the functional importance of these different components is unclear. Using optogenetic stimulation, Rainer Friedrich and colleagues examine directly the downstream readout of oscillatory bulb activity in the posterior zone of the dorsal telencephalon (Dp), a zebrafish homologue of the olfactory cortex. Dp neurons were largely insensitive to synchronized oscillatory activity, but respond to steady-state activity. These findings could be accounted for by low-pass filter-like biophysical properties of Dp neurons, and demonstrate how filtering can extract individual components of neuronal codes.

Munc18-1 has an important role in neurotransmitter release, and controls every step in the exocytotic pathway in the central nervous system. In the present study, whether epileptic seizure causes a change of Munc18 localization in neuronal nuclei was analyzed.Epilepsy models were established by injection of kainic acid (KA) solution into hippocampus of Sprague-Dawley (SD) rats or intraperitoneal injection of KA in Kunming mice. The hippocampal neurons were prepared from embryonic day 18 SD rats, and cultured in neurobasal medium, followed by treatment with glutamate for 3 h. Neuronal and glial nuclei of hippocampus were separated by sucrose density gradient centrifugation. The nucleus-enriched fractions were stained with 0.1% Cresyl Violet for morphological assay. Immunochemistry and immunoelectron microscopy with anti-Munc18-1 antibody were used to determine the nuclear localization of Munc18-1. Immunoblotting was used to detect the protein level of Munc18-1.The localization of Munc18-1 in nucleus of rat hippocampal neuron was confirmed by immunochemistry, immunoelectron microscopy, and immunoblotting detection of neuronal nucleus fraction. In animals receiving intrahippocampal or intraperitoneal injection of KA, immunostaining revealed that the expression of Munc18-1 decreased in pyramidal cell layer of CA regions, as well as in hilus and granular cell layer of dentate gyrus in hippocampus. Moreover, immunoblotting analysis showed that the expression level of Munc18-1 in nucleus fraction of hippocampus significantly decreased in KA-treated animals. The relationship between the change of Munc18-1 expression in neuronal nuclei and neuronal over-activation was also tested in primary cultured neurons. After treatment with 50 μmol/L glutamate acid for 3 h, Munc18-1 level was decreased in nucleus fraction and increased in cytoplasmic fraction of primary cultured neurons.These results suggest that excitatory stimulation can induce the distribution change of Munc18-1 in neuron, which may subsequently modulate neuronal functions in brain.

Biologically utilizable dissolved organic compounds, including dissolved organic carbon (DOC), dissolved carbohydrates (DCHO) and dissolved free amino acids (DFAA) were analyzed in filtered surface seawater samples collected at 19 stations in Jiaozhou Bay, China, on June 3, 2007. In these samples, concentrations of DOC, dissolved free carbohydrates (DFCHO), dissolved combined carbohydrates (DCCHO), total dissolved carbohydrates (TDCHO) and total dissolved free amino acids (TDFAA) ranged from 141.7 to 191.1 µmol C/L, 1.98 to 18.18 µmol C/L, 5.04 to 24.90 µmol C/L, 14.52 to 30.36 µmol C/L, and 1.83 to 11.89 µmol C/L, respectively. As a major component of the dissolved carbohydrates, the concentrations of DCCHO were about three times higher than those of DFCHO. Three major constituents of the DFAA were threonine (23.0±5.7 mol%), glutamic acid (16.6±3.2 mol%) and arginine (9.1±3.3 mol%). Based on the composition of DFAA, a molar C:N ratio of 3.60±0.75 in DFAA was derived, indicating longer carbon chains in the amino acids. DCCHO (8.1%) was the most abundant fraction of DOM in most samples, followed by DFCHO (4.8%) and TDFAA (2.7%). These DOM concentrations displayed a decreasing trend from the coast to the central region. Significant correlations were found between the DCCHO and DFCHO concentrations (r=-0.724, n=19, P

Taxus yunnanensis Cheng et L. K. Fu is a rare species endemic to Southeast Asia. The development of the male reproductive structures with emphasis on microsporogenesis and microgametogenesis are described for the first time. Our results showed that T.yunnanensis exhibits several features that are very different from other species of Taxus, such as pollination occurring in the same year as pollen cone initiation; production of several forms of tetrads including isobilateral, T-shaped or tetrahedron; shorter duration of microsporogenesis; longer duration of microgametogenesis; and production of more microsporophylls per pollen cone suggesting faster growth rate. Reports on the details of male reproductive development in Taxus spp. have focused on the activities of generative nuclei, while the activities of the sterile and tube nuclei are rarely mentioned. This paper provides a few more details about the sterile and tube nuclei, particularly, their relative position during the division of the generative nucleus to form two sperm. Furthermore, as our knowledge of the phenology of Taxus is confined to species that grow on high latitude areas, this paper provides information on the phenology of Taxus in low latitude areas. Overall, this paper provides several new insights about pollen cone development, microsporogenesis, and microgametogenesis in Taxus.

Twenty-four provenances of two species (Azadirachta siamensis and Azadirachta indica) have been introduced to China from South Asia, Southeast Asia and Africa Since 1995. This paper summarizes the researches on the introduction and planting of Azadirachta indica and analyzes the morphological, phenological characteristics, the growth rhythm, pollinating and seed yielding features of the intro-duced 24 provenances of the two species as well as the variations of filial generation plants. The experiments showed that most of the provenances of A. indica have normal growth and can blossom and fruit in the dry-hot valleys with tropical climate conditions in Yunnan Province, China. The normal regions for A. indica were classified and the selection criteria for superior plants were put forward in this paper, moreover, the major contents of industry planning and technical approaches for A. indica plantation establishment were discussed and the countermeasures to reduce the neem-based pesticide products were also proposed.

A new complex [Co(H2pztc)(bpy)H2O] (H4pztc = pyrazine-2,3,5,6-tetracarboxylic acid, bpy = 2,2′-bipyridine) has been synthesized by hydrothermal reactions of Co(NO3)2 · 6H2O with H4pztc and bpy and characterized by IR and X-ray diffraction single crystal structure analysis. It belongs to monoclinic system, P21/c space group with a = 13.454(2) A, b = 12.939(2) A, c = 11.4993(19) A, α = 90°, β = 111.640(3)°, γ = 90°. This complex is assembled into 3D supramolecular architecture by hydrogen bonds (O–H···O, C–H···O). A new complex of cobalt(II) with pyrazine-2,3,5,6-tetracarboxylic acid and 2,2′-bipyridine is assembled by intermolecular hydrogen bonds forming 2D layer and 3D supramolecular network.

The spectra of highly charged titanium ions produced by the interaction of 120 MeV titanium ions with carbon foil were investigated with the so-called beam-foil technique using the HI-13 tandem accelerator in China Institute of Atomic Energy. Spectral lines emitted from fifty-three excited energy levels were observed in the wavelength range 120–220 A, among which eleven lines were new. Our experimental results show good agreement with the results of laser plasma experiments, and are in reasonable agreement with theoretical calculations.

Objective: To investigate the effects of Reduqing (RDQ, Open image in new window ) on plasma interleukin-8 (IL-8), NO2 - /NO3 -, complement 5a (C5a) and polymorphonuclear neutrophilic leukocyte (PMN) chemotaxis Index (CI) in rabbits with endotoxin-induced disseminated intravascular coagulation (DIC).Methods: Endotoxin-in-duced DIC model made by injection of Lipopolysacchrides (LPS) was used in the experiment. Above-mentioned indexes were determined before and after RDQ treatment and compared with blank and dexamethasone treated group.Results: Plasma IL-8, NO2 - /NO3 -, C5a and CI level of PMN increased markedly in the model group, which were confirmed pathologically with obvious damage of tissues or organs. In the RDQ group, the abovem entiond parameters and damage of tissues or organs were reduced significantly (P < 0.01).Conclusion: IL-8 and NO might be involved in pathogenesis of endotoxin-induced DIC, and RDQ could be used in preventing or treating DIC through the mechanism of regulation of cytokines network.

We have combined millisecond activation of channelrhodopsin-2 (ChR2), a light-gated ion channel, with two-photon calcium imaging to investigate active synaptic contacts in rat hippocampal slice cultures. Calcium influx was larger during light-induced action potentials than during action potentials induced by somatic current injection, leading to highly reproducible synaptic transmission. Pairing of light stimulation with postsynaptic depolarization induced long-term potentiation, making this technique ideal for genetic and pharmacological dissection of synaptic plasticity.

The clinical potential of mixed amine platinum(IV) complexes has been identified, and interest in this new class of antitumor agents has been heightened by demonstration of their activity in cisplatin-resistant neoplasms. These tetravalent platinum agents are expected to undergo a reductive reaction to form the corresponding platinum(II) drug prior to eliciting biological activity. cis-Ammine/cyclohexylamine-dichloroplatinum(II) is one such product that we evaluated with cisplatin in vivo, and we found the two complexes given i.v. or i.p. to have comparable activities against a solid murine fibrosarcoma. Following i.v. administration of the two compounds at equitoxic dose levels (20 mg/kg) to tumor-bearing mice, platinum levels in the plasma were consistently higher for cisplatin. Tissue platinum levels, in contrast, were comparable between the agents or higher for the mixed amine analog at the earliest (3-h) time point. The temporal profiles determined for the concentrations over 48 h were tissue- and/or drug-specific and could be described by terminal-phase constants or half-lives of platinum in most tissues. In the plasma, kidney, lung, and jejunum, platinum levels arising from both compounds decayed with half-lives of 24-92 h. The terminal-phase constants of platinum determined in the heart for the two complexes were not significantly different from zero, indicative of levels remaining steady, whereas the constants were negative in the spleen, indicative of an increase in tissue drug concentration. In the tumor, liver, and testes, positive values for the decay-phase constants corresponding to half-lives of 47, 256, and 79 h, respectively, were seen with the mixed amine complex; this pattern contrasted with that found for cisplatin, for which the terminal-phase constant was either zero or negative. In vitro binding studies demonstrated the mixed amine complex to be more reactive. Thus, the presence of one ammine and one cyclohexylamine carrier ligand in the mixed amine complex, as opposed to the diammine ligands in cisplatin, leads to an increase in drug distribution and an alteration in the kinetics of tissue binding and removal of platinum.

Introduction The present study was designed to determine the possibility of acetylbritannilactone (ABL) derivative 5-(5-(ethylperoxy)pentan-2-yl)-6-methyl-3-methylene-2-oxo-2,3,3a,4,7,7a-hexahydrobenzofuran-4-yl 2-(6-methoxynaphthalen-2-yl)propanoate (ABL-N) as a novel therapeutic agent in human breast cancers. Methods We investigated the effects of ABL-N on the induction of apoptosis in human breast cancer cells and further examined the underlying mechanisms. Moreover, tumor growth inhibition of ABL-N was done in xenograft models. Results ABL-N induced the activation of caspase-3 in estrogen receptor (ER)-negative cell lines MDA-MB-231 and MDA-MB-468, as evidenced by the cleavage of endogenous substrate Poly (ADP-ribose) polymerase (PARP). Pretreatment of cells with pan-caspase inhibitor z-VAD-fmk or caspase-3-specific inhibitor z-DEVD-fmk inhibited ABL-N-induced apoptosis. ABL-N treatment also resulted in an increase in the expression of pro-apoptotic members (Bax and Bad) with a concomitant decrease in Bcl-2. Furthermore, c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase (p38) were activated in the apoptosis induced by ABL-N and JNK-specific inhibitor SP600125 and JNK small interfering RNA (siRNA) antagonized ABL-N-mediated apoptosis. However, the p38-specific inhibitor SB203580 had no effect upon these processes. Moreover, neither of the caspase inhibitors prevented ABL-N-induced JNK activation, indicating that JNK is upstream of caspases in ABL-N-initiated apoptosis. Additionally, in a nude mice xenograft experiment, ABL-N significantly inhibited the tumor growth of MDA-MB-231 cells. Conclusions ABL-N induces apoptosis in breast cancer cells through the activation of caspases and JNK signaling pathways. Moreover, ABL-N treatment causes a significant inhibition of tumor growth in vivo. Therefore, it is thought that ABL-N might be a potential drug for use in breast cancer prevention and intervention.