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Spurs have played an important role in the radiation of the genus Aquilegia, but little is known about how the spurless state arose in A. ecalcarata. Here we aim to characterize the genetic divergence within A. ecalcarata and gain insights into the origin of this species. A total of 19 populations from A. ecalcarata and 23 populations from three of its closest relatives (Aquilegia kansuensis, Aquilegia rockii and Aquilegia yabeana) were sampled in this study. We sequenced fifteen nuclear gene fragments across the genome and three chloroplast loci to conduct phylogenetic, PCoA and STRUCTURE analyses. Our analyses indicate that A. ecalcarata may not be monophyletic and can be divided into two distinct lineages (A. ecalcarata I and A. ecalcarata II). A. ecalcarata I is genetically close to A. kansuensis, whereas A. ecalcarata II is close to A. rockii. Isolation-with-migration analysis suggested that historical gene flow was low between A. ecalcarata I and A. rockii, as well as between A. ecalcarata II and A. kansuensis. The two distinct lineages of A. ecalcarata show significant divergence in 13 floral traits and also have distinct distributions. In addition, both A. ecalcarata I and II are adapted to a stony environment that differs from that of their closest relatives, indicating a habitat shift may have driven new adaptations. Our findings enrich the understanding of how floral evolution contributes to species diversification.

S1: Analytical methods. S2: Detailed descriptions of the results of zircon and monazite age dating. S3: Supplementary Figures. S4: Supplementary Tables. Supplemental Dataset.

The hybrid tracked vehicles(HTV) usually adopt series hybrid powertrain with extra steering mechanism, which has relatively low transmission efficiency and reduces the flexibility of structural arrangement. To overcome the disadvantages, a new kind of single-mode powertrain has been proposed. The power-split hybrid powertrain is composed of three planetary gear (PG) sets connected to one engine, left and right track outputs, and three motors. The proposed powertrain can realize steering while going forward by controlling the output torque on each side without extra steering mechanism or steering shaft. Due to the diversity of the connection way between components and planetary gear sets, a rapid configuration design approach is proposed for the design selection of HTV. The automated dynamic modelling method can show the one-to-one correspondence with the selected feasible groups by establishing two characteristic matrices, which is more simple than other researches. The analytically-based method is proposed to classify all possible connection designs into several groups to decrease the searching scope with improved design efficiency. Finally, the optimal control strategy is used to find the design with optimal fuel economy under typical condition of HTV. The case study is implemented by the proposed design approach which demonstrates better design performances compared with the existing series-hybrid HTV.

This study considers the Upper Cretaceous Qingshankou Formation, Yaojia Formation, and the first member of the Nenjiang Formation in the Western Slope of the northern Songliao Basin. Dark mudstone with high abundances of organic matter of Gulong and Qijia sags are considered to be significant source rocks in the study area. To evaluate their development characteristics, differences and effectiveness, geochemical parameters are analyzed. One-dimensional basin modeling and hydrocarbon evolution are also applied to discuss the effectiveness of source rocks. Through the biomarker characteristics, the source–source, oil–oil, and oil–source correlations are assessed and the sources of crude oils in different rock units are determined. Based on the results, Gulong and Qijia source rocks have different organic matter primarily detrived from mixed sources and plankton, respectively. Gulong source rock has higher thermal evolution degree than Qijia source rock. The biomarker parameters of the source rocks are compared with 31 crude oil samples. The studied crude oils can be divided into two groups. The oil–source correlations show that group I oils from Qing II–III, Yao I, and Yao II–III members were probably derived from Gulong source rock and that only group II oils from Nen I member were derived from Qijia source rock.

Two rare guanidine-type alkaloids, Buthutin A (1) and Buthutin B (2), along with two other compounds (3, 4), were isolated from Buthus martensii Karsch, and determined using extensive spectroscopic data analysis and high resolution-mass spectrometry. Compound 1 showed the most potent inhibition on AChE and BChE with IC50 values of 7.83 ± 0.06 and 47.44 ± 0.95 μM, respectively. Kinetic characterization of compound 1 confirmed a mixed-type of AChE inhibition mechanism in accordance with the docking results, which shows its interaction with both catalytic active (CAS) and peripheral anionic (PAS) sites. The specific binding of compound 1 to PAS domain of AChE was also confirmed experimentally. Moreover, compounds 1 and 3 exhibited satisfactory biometal binding abilities toward Cu2+, Fe2+, Zn2+ and Al3+ ions. These results provide a new evidence for further development and utilization of B. martensii in health and pharmaceutical products.

Thyroid cancer is common in China. Thyroid adenocarcinoma metastases can be local or distal metastasis. Local metastasis presents as a hard and fixed lymph node in the neck, while distant metastases are found in the lung, skull, vertebrae, and pelvis. However, thyroid follicular carcinomas are mostly observed in hematogenous metastases. The thyroid adenocarcinoma and follicular carcinoma of the thyroid gland are often misdiagnosed. Here, we report the case of a 53-year-old female patient. More than 2 years after her initial diagnosis, her left chest wall was physically examined. The results revealed a progressive enlargement that had a hard quality, poor activity, unclear boundary, pressure pain, and percussion pain. Thyroid follicular cell carcinoma was subsequently diagnosed and treated surgically. The thyroid carcinoma had multiple bone metastases, and the thyroid follicular carcinoma had spread to the chest wall through the blood vessels. Thus, preoperative procedures and follow-up should be strengthened because early pathological thyroid follicular carcinoma and thyroid adenoma can easily be misdiagnosed. Pathologic consultation and follow-ups should be strengthened to prevent misdiagnosis.

The International League Against Epilepsy (ILAE) defined drug‐resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well‐tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%‐40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.

Spurs have played an important role in the radiation of the genus

With the development of intelligent transportation system, intelligent network technology has been studied on a large scale in vehicle field. Electrification of vehicles and drive-by-wire chassis provide possibilities for the application of connected autonomous electrified vehicles. Regenerative braking control is an important field among drive-by-wire chassis control technologies. Regenerative braking control is a multi-objective optimization problem, which has the aim of improving regenerative energy efficiency, brake performance, and brake comfort. Therefore, a model predictive control (MPC) is proposed to solve the problem with consideration of different brake styles, such as aggressive, moderate and conservative. Then, the models of the main components associated with the regenerative braking system are designed and built up in a typical deceleration process for simulation and analysis. The simulation results show that the aggressive style mode is the best brake performance, which cause issues on brake comfort as well. The conservative style mode makes full use of motor braking and has advantage of the brake comfort and regenerative energy efficiency. But, it is not good at rapid braking performance of low brake intensity. The moderate style mode is suitable for most drivers, which is balanced of the above characteristics. Finally, experimental tests under ECE driving cycle are also carried out to further verify the characteristics of proposed three brake modes.

Sheet-like MoSe2/C nanocomposites were synthesized and employed as the cathode of a rechargeable Mg2+/Li+ hybrid battery for the first time, which exhibited an excellent electrochemical performance. The structure transformation of the MoSe2/C nanocomposite materials during the charge-discharge processes was identified by in situ XRD, and the electrochemical reactions taking place in the battery were evidenced. Keywords: In situ XRD, Sheet-like MoSe2/C nanocomposites, Mg2+/Li+ hybrid battery

Effects of Rosemary Antioxidanton, extracted from Rosmarinus officinalis with different solvents, on the antioxidantive properties of polypropylene were evaluated by measuring the oxidation induction temperature. For comparison purposes, the effects of a synthetic phenolic commercial antioxidant Irganox B215, were also analyzed. The results showed that Rao is a more efficient thermal antioxidant for polymers compared to Irganox B215 in low concentration. Rao can be used as a natural antioxidant in place of synthetic antioxidants for polymers. Rao has the characteristic of being harmless and having high activity, good stability and abundant resources to be a good natural antioxidant.

Effects of Rosemary Antioxidanton (Rao), extracted from Rosmarinus officinalis, on the antioxidantive properties of polypropylene were evaluated by investigating the difference of mechanical properties and melt flowability between pre and post natural weathering tests. For comparison purposes, the effects of a synthetic phenolic commercial antioxidant (Irganox B215), were also analyzed. The results showed that the reduction of mechanical properties and the increment of melt flowability of polypropylene containing Rao were slower than that of the unstabilized reference during the aging process, which implies that Rao exhibits high efficiency as a thermal antioxidant for polypropylene. On the other hand, samples that contained Irganox B215 obtained further improved stability over the samples containing Rao during 105 days; however, the effectiveness of Rao lasted longer than that of Irganox B215. Rao has the characteristic of being harmless and having high activity, good stability and abundant resources to be a good natural antioxidant.

Aim To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newly-onset cytomegalovirus retinitis (CMVR). Methods The retrospective study observed 37 patients (58 eyes) who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus (CMV) in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection. Results CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients' aqueous decreased from 38.3×104 copies/mL at baseline to 2.2×104 copies/mL after the 4th injection in patients who were treated with ganciclovir monotherapy, and decreased from 76.9×104 copies/mL to 11.3×104 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy. Conclusion Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.

In order to resolve the problems of the torque sensor, including the principles and structure can not be reflected, the measurement results to be idealized and the noise can't be presented in the MATLAB/simulink simulation environment. The simulation model of train-resistor Torque Sensor consists of three modules: the strain axis module to realize transformation the torque to the strain, bridge module including four strain gauges, bridge output voltage. The model output is 0 to 5V voltage, measurement results contain Gaussian distribution errors, which make simulation system to better reflect the real objects, at the same time for more detailed study of the torque sensor and pave the way.

Objective To observe the promotion effect of bone mesenchymal stem cells (BMSCs) transplantation and mobilized bone marrow stem cells on the recovery of liver function and liver tissue regeneration after massive partial hepatectomy in rats. Methods The rats were randomly divided into four groups after massive partial hepatectomy (about 85%), namely massive hepatectomy group (control group, n=15, received massive hepatectomy only), G-CSF group [n=15, received rhG-CSF 150μg/(kg•d) by intraperitoneal injection after the operation for 5 days], MSCs group [n=15, received 5ml suspension of MSCs (about 1.5×106) by tail vein injection after the operation], and G-CSF+MSCs group [n=14, received 1.5ml suspension of MSCs (about 1.5×106) by tail vein injection and rhG-CSF 150μg/(kg•d) by intraperitoneal injection for 5 days after the operation]. The CD34+ cells in the peripheral blood of the rats were assessed by flow cytometry after G-CSF mobilization. Liver function tests including ALT, AST and ALB were performed on the 3rd and 9th day after surgery. All the rats were sacrificed and liver tissue was harvested for histopathological study. The expression of Ki-67 and BrdU positive cells in the liver were determined by immunohistochemistry. Results Flow cytometric results identified the isolated cells were MSCs. BMSCs in peripheral blood significantly increased in number after rhG-CSF mobilization, and reaching the maximum number on the 5th day. After mobilization for 3, 5 and 9 days, the positive CD34 cells in G-CSF group were 0.009%, 0.016%, 0.019% respectively, which were higher than those in control group. The level of albumin was significantly elevated in three treatment groups compared with control group on the 9th day after the hepatectomy (P

ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis1. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important2, 3. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography–mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

A series of new 4-N-phenylaminoquinoline derivatives were designed, synthesized, and their anticholinesterase activities, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal-chelating ability were tested. Among them, compounds 11j, 11k and 11l had comparable inhibition activities to reference drug galantamine both in AChE and in BChE. Especially, compound 11j revealed the most potent inhibition to eeAChE and eqBChE with IC50 values of 1.20 μM and 18.52 μM, respectively. Furthermore, both kinetic analysis of AChE inhibition and molecular docking study indicated that compound 11j was mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE, and propidium iodide displacement assay showed significant displacement of propidium iodide with compound 11k (25.80%) from PAS of eeAChE. More importantly, compound 11l displayed excellent DPPH radical scavenging activity (84% at 1 mg/mL), and its EC50 value was 0.328 μM. In addition, compounds 11a, 11j, 11k and 11l exhibited obvious biometal chelating abilities toward Al3+, Fe2+, Cu2+ and Zn2+ ions. Taken together, 4-N-phenylaminoquinoline derivatives targeting multiple pathogenetic factors deserve further investigation for treatment of AD.

Objectives: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. Methods: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4′,6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2′-deoxyuridine. Results: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4′,6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2′-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. Conclusion: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.

Computations of wall distances still play a key role in modern turbulence modeling. Motivated by the expense involved in the computation, an approach solving partial differential equations is considered. An Euler-like transport equation is proposed based on the Eikonal equation. Thus, the efficient algorithms and code components developed for solving transport equations such as Euler and Navier-Stokes equations can be reused. This article provides a detailed implementation of the transport equation in the Cartesian coordinates based on the code of computational fluid dynamics for missiles (MICFD) of Beihang University. The transport equation is robust and rapidly convergent by the implicit lower-upper symmetric Gauss-Seidel (LUSGS) time advancement and upwind spatial discretization. Geometric derivatives must also be upwind determined to ensure accuracy. Special treatments on initial and boundary conditions are discussed. This distance solving approach is successfully applied on several complex geometries with 1–1 blocking or overset grids.

The impact of oncogene activation and hypoxia on energy metabolism is analyzed by integrating quantitative measurements into a redox-balanced metabolic flux model. Glutamine-driven oxidative phosphorylation is found to be a major ATP source even in oncogene-expressing or hypoxic cells., The integration of oxygen uptake measurements and LC-MS-based isotope tracer analyses in a redox-balanced metabolic flux model enabled quantitative determination of energy generation pathways in cultured cells. In transformed mammalian cells, even in hypoxia (1% oxygen), oxidative phosphorylation produces the majority of ATP. The oncogene Ras simultaneously increases glycolysis and decreases oxidative phosphorylation, thus resulting in no net increase in ATP production. Glutamine is the major source of high-energy electrons for oxidative phosphorylation, especially upon Ras activation., Mammalian cells can generate ATP via glycolysis or mitochondrial respiration. Oncogene activation and hypoxia promote glycolysis and lactate secretion. The significance of these metabolic changes to ATP production remains however ill defined. Here, we integrate LC-MS-based isotope tracer studies with oxygen uptake measurements in a quantitative redox-balanced metabolic flux model of mammalian cellular metabolism. We then apply this approach to assess the impact of Ras and Akt activation and hypoxia on energy metabolism. Both oncogene activation and hypoxia induce roughly a twofold increase in glycolytic flux. Ras activation and hypoxia also strongly decrease glucose oxidation. Oxidative phosphorylation, powered substantially by glutamine-driven TCA turning, however, persists and accounts for the majority of ATP production. Consistent with this, in all cases, pharmacological inhibition of oxidative phosphorylation markedly reduces energy charge, and glutamine but not glucose removal markedly lowers oxygen uptake. Thus, glutamine-driven oxidative phosphorylation is a major means of ATP production even in hypoxic cancer cells.

Increasing evidence has revealed that thy-1 was a potential stem cell marker of liver cancer, but no data have been shown on how thy-1 regulates the pathophysiology of liver cancer, such as proliferation, apoptosis, invasion and migration. We previously demonstrated that thy-1 was expressed in about 1% of hepg2 cells, thy-1+ hepg2 cells, but not thy-1-, demonstrating high tumorigenesis on inoculation 0.5x10⁵ cells per BACA/LA mouse after 2 months. In the present study, our results showed that higher expression of thy-1 occurs in 72% (36/50 cases) of neoplastic hepatic tissues as compared to 40% (20/50 cases) of control tissues, and the expression of thy-1 is higher in poorly differentiated liver tumors than in the well-differentiated ones. In addition, thy-1 expression was detected in 85% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis or hepatitis. There was a significant negative correlation between thy-1 expression and E-cadherin expression (a marker of invasion and migraton), but not between thy-1 expression and AFP expression in all the liver cancer and blood samples. We further investigated the relationship between thy-1 and E- cadherin in liver cancer hepg2 cell line which was transfected with pReceiver-M29/thy-1 eukaryotic expression vector followed by aspirin treatment. Lower expression of E- cadherin but higher expressions of thy-1 were detected in hepg2 cells transfected with pReceiver-M29/thy-1. Taken together, our study suggested that thy-1 probably regulates liver cancer invasion and migration.

In the title complex, [Ni(C9H5O6)2(C11H10N4)2]·8H2O, the Ni(II) ion exhibits site symmetry 2. It has a distorted octa-hedral coordination defined by two N atoms from two symmetry-related 1-[(1H-benzimidazol-1-yl)meth-yl]-1H-imidazole ligands and four O atoms from two symmetry-related 3,5-dicarb-oxy-benzoate anions. In the crystal, the complex mol-ecules and solvent water mol-ecules are linked via O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds, forming a three-dimensional structure. There are also a number of C-H⋯O inter-actions present.

Abstract 4929 Benzene is a volatile aromatic hydrocarbon solvent which is widely used in many industries. The chronic exposure of humans to benzene in the workplace has been associated with blood disorders, as well as toxicity in lymphopoiesis, including aplastic anemia and leukemia. Our previous study showed that skewed distribution and clonal expansion of TCR Vα/ Vβ subfamily T cells and changed CD3ζ gene expression in benzene-exposed workers. Little is known about the expression feature of CD3γ, CD3δ and CD3ε genes, which are also involved TCR signal transduction. To further identify the feature of CD3 complex gene in benzene-exposed workers, real-time PCR with SYBR Green I technique was used for detecting CD3γ, CD3δ, CD3ε gene expression level in peripheral blood mononuclear cells from 16 benzene-exposed workers, 8 chronic mild benzene-poisoning workers, 9 chronic middling benzene-poisoning workers and 9 chronic severely benzene-poisoning workers, respectively. Control group consisted of 26 healthy individuals. β2-microglobulin gene was used as an endogenous reference. Relative changes in these gene expression level was used by the 2ΔCt×100% method. The CD3γ gene expression in benzene-exposed (2.99±3.10) and each benzene-poisoned group (2.13±2.16, 2.65±1.73 and 1.29±0.74, respectively) decreased significantly compared with that of in healthy individuals (5.97±4.86) (P< 0.05). The CD3δ gene expression in benzene-exposed group (8.38±9.6) increased significantly compared with those from healthy individuals (1.09±1.1) (P< 0.05), while in each benzene-poisoned group (2.57±2.51, 1.60±2.55 and 0.74±0.51, respectively), decreased significantly compared with those from benzene-exposed (P< 0.05). No significant difference was found in expression level of CD3ε between the healthy group, benzene-exposed, different benzene-poisoning groups (5.95±6.94, 6.60±6.31, 7.01±5.99, 4.33±4.69, 3.73±4.48, respectively) (P> 0.05). In conclusions, the abnormality expression of CD3γ and CD3δ gene is also a common feature in benzene-exposed and benzene-poisoned workers, which might participate in part of T cell immune dysfunction. Disclosures: Li: Natural Science Foundation of Guangdong province (No. 07301046): Research Funding; Medical Science Technology Program of Guangzhou (2009-ZDI-18): Research Funding; Natural Science Foundation of Guangdong province (No. 07301046): Research Funding; China Postdoctoral Science Foundation funded project (No. 20070410840): Research Funding; National Natural Science Foundation of China (No. 30972455): Research Funding. Fan:Undergraduate Science and Technology Innovation project of Guangdong (1055911020): Research Funding. Wang:Undergraduate Science and Technology Innovation project of Guangdong (1055911020): Research Funding. Chen:Undergraduate Science and Technology Innovation project of Guangdong (1055911020): Research Funding. Chen:Medical Science Technology Program of Guangzhou□(2009-ZDI-18): Research Funding. Li:Medical Science Technology Program of Guangzhou(2009-ZDI-18): Research Funding; The Fundamental Research Funds for the Central Universities□iNo. 2011610408□j: Research Funding; Natural Science Foundation of Guangdong province (No. 07301046): Research Funding; China Postdoctoral Science Foundation funded project (No. 20070410840): Research Funding; National Natural Science Foundation of China (No. 30972455): Research Funding.