The integration of dinitropyrazole and 1,3,4-oxadiazole:A novel hybrid heterocyclic skeleton for balancing energy and stability

In this study,a new energetic hybrid skeleton was constructed through the integration of nitropyrazole and 1,3,4-oxadiazole skeletons in a molecule.Furthermore,the energetic precursor(2),the azo-bridged compound(3),the neutral nitramine(4)and the corresponding energetic salts(5-7)were synthesized.Their physicochemical and energetic properties we re experimentally and theo retically evaluated.Among the developed compounds,the azo-bridged compound(3)and dihydroxylammoinium(6)display high detonation performances(3,D_(v)=8904 m/s,P=34.47 GPa;6,D_(v)=9025 m/s,P=34.66 GPa),moderate sensitivities(3,IS=16 J,FS=120 N;6,IS=20 J,FS=312 N)and good densities(3,1.87 g/cm^(3);6,1.81 g/cm^(3)),which indicates that they have the potential to replace the traditional high-energy explosive RDX.The results show that the integration of different energetic skeletons can achieve a good balance between energy and sensitivity.

Divalent nitrogen-rich cationic salts with great gas production capacities

Monocyclic nitrogen-rich 3-(aminomethyl)-4,5-diamine-1,2,4-triazole(1)and fused cyclic 3,7-diamine-6-(aminomethyl)-[1,2,4]triazolo[4,3-b][1,2,4]triazole(9)were synthesized through the convenient cyclization reaction from the readily available reactant.Their energetic salts with high nitrogen content were proved to be rare examples of divalent monocyclic/fused cyclic cationic salts according to the single crystal analyses.The structure of intermediate B was also identified and verified by its trivalent cation crystal 17.5H_2O indirectly.Energetic compounds 2-8 and 10-17 were fully characterized by NMR spectroscopy,infrared spectroscopy,differential scanning calorimetry,elemental analysis.These energetic salts exhibit good thermal stability with decomposition temperatures ranged from 182℃to 245℃.The sensitivity of compounds 2,6,10 and 14 is similar or superior to that of RDX while the others were much more insensitive to mechanical stimulate.Furthermore,detonation velocity of 10(8843 m/s)surpass that of RDX(D=8795 m/s).Considering the high gas production volume(≥808 L/kg)of 2,4,10and 12,constant-volume combustion experiments were conduct to evaluate their gas production capacities specifically.These compounds possess much higher maximum gas-production pressures(P_(max):7.88-10.08 MPa)than the commonly used reagent guanidine nitrate(GN:P_(max)=4.20 MPa),which indicate their strong gas production capacity.

A developed transient gas-liquid-solid flow model with hydrate phase transition for solid fluidization exploitation of marine natural gas hydrate reservoirs

The multiphase flow characteristic is one of the most concerning problems during solid fluidization exploitation of marine natural gas hydrate reservoirs.In this research,a new transient gas-liquid-solid multiphase flow model with hydrate phase transition was developed.Meanwhile,this model considered the coupling relationship among convective heat transfer,hydrate dynamic decomposition,and multi-phase flow.The model can simulate the change of flow pattern from solid-liquid to gas-liquid-solid flow,and describe the distribution character of volume fraction of phase,wellbore temperature and pressure,and hydrate decomposition rate during transportation.The simulation results indicate that the hydrate decomposition region in the wellbore gradually expands,but the hydrate decomposition rate gradually decreases during the solid fluidization exploitation of hydrate.When mining time lasts for 4 h,and the bottom hole pressure decreases by about 0.4 MPa.Increasing NaCl concentration in seawater helps expand hydrate decomposition regions and improves the wellbore hydrate decomposition rate.When the Nacl mass fraction in seawater reaches 15%,it will raise the hydrate decomposition regions to the whole wellbore.In addition,the higher the wellhead backpressure,the lower the decomposition area and decomposition rate of hydrate in the wellbore.When wellhead backpressure reaches 2 MPa,the volume fraction of gas near the wellhead will reduce to about 12%.This work is expected to provide a theoretical basis for the development of marine hydrate reservoirs.

A novel energetic framework with the combination of 5,6-fused triazolo-triazine and nitropyrazole-tetrazole for energy-stability balanced explosive

In recent years,the introduction of fused rings own high density and low sensitivity has promoted the development of energetic materials.However,the development of energetic compounds containing fused and bridged rings by introducing multiple nitrogen heterocycles at different sites of fused rings is still difficult to progress,which seriously limits the emergence of advanced energetic compounds.In this study,a series of energetic materials choosing different nitrogen rich heterocycles at the vacancies of the fused ring,i.e.,neutral compound 5,6 and their ionic derivatives(compounds 7-12)were designed and synthesized.Compounds 5 and 6 were further confirmed by single crystal X-ray diffraction,while the crystal analysis and theoretical calculations were carried out to explore the relationship between crystal structure and physicochemical properties.All of the newly synthesized compounds(5-12)are insensitive to mechanical stimulation(IS>40 J;FS≥342 N)and they own the high detonation velocity(D:8322-9075 m/s).Notably,hydrazine salt 11 own the higher detonation velocity(9075 m/s)and powder density(1.83 g/cm^(3)),but exhibits lower sensitivity(IS>40 J)than the classical energetic compound RDX(8795 m/s,1.80 g/cm^(3),7.5 J).It is obvious that the combination of 5,6-fused triazolo-triazine and nitropyrazole-tetrazole may be a new energetic skeleton for synthesising the heterocyclic compounds with balanced energy-stability.

Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression

Quercetin is a widely-occurring flavonoid that protects against cancer, and improves memory and cardiovascular functions.However, whether quercetin exhibits therapeutic effects in diabetic retinopathy remains unclear.In this study, we established a rat model of streptozocininduced diabetic retinopathy.Seventy-two hours later, the rats were intraperitoneally administered 150 mg/kg quercetin for 16 successive weeks.Quercetin markedly increased the thickness of the retinal cell layer, increased the number of ganglion cells, and decreased the overexpression of the pro-inflammatory factors interleukin-1β, interleukin-18, interleukin-6 and tumor necrosis factor-α in the retinal tissue as well as the overexpression of high mobility group box-1 and the overactivation of the NLRP3 inflammasome.Furthermore, quercetin inhibited the overexpression of TLR4 and NF-κBp65, reduced the expression of the pro-angiogenic vascular endothelial growth factor and soluble intercellular adhesion molecule-1, and upregulated the neurotrophins brain-derived neurotrophic factor and nerve growth factor.Intraperitoneal injection of the heme oxygenase-1 inhibitor zinc protoporphyrin blocked the protective effect of quercetin.These findings suggest that quercetin exerts therapeutic effects in diabetic retinopathy possibly by inducing heme oxygenase-1 expression.This study was approved by the Animal Ethics Committee of China Medical University, China(approval No.2016 PS229K) on April 8, 2016.

Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

AIM: To investigate the expression and role of nuclear factor κB(NF-κB) in diabetic retinopathy(DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS: A total of 80 male Wistar rats were randomly assigned to control(4, 8, 12 and 16 wk, n =10 in each group) and diabetes mellitus(DM) groups(4, 8, 12 and 16wk, n =10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin(60 mg/kg). After 4, 8, 12 and 16 wk, rats were sacrificed.Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by Td T-mediated d UTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS: DM model success rate up to 100%.Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group(P 【0.01). After 12 wk other pathological changes in the retina of diabetic rats were observed; after 16 wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed.Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration.CONCLUSION: With the prolonging of DM progression,the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization.

Health and Economic Impacts of Air Pollution in China: A Comparison of the General Equilibrium Approach and Human Capital Approach

In China, combustion of fossil fuels and biomass has produced serious air pollution that does harm to human health. Based on dose-response relationships derived from epidemiological studies, the authors calculated the number of deaths and people with health problems which were thought to be attributable to China＇s air pollution in the year of 2000. In order to estimate the corresponding economic impacts from the national point of view, the general equilibrium approach was selected as an analysis tool for this study. A computable general equilibrium （CGE） model was constructed involving 39 sectors and 32 commodities. The human capital approach （HCA） was also used for comparison. The economic burden of disease for people estimated by HCA was equivalent to 1.26‰ （ranging from 0.44‰ to 1.84‰） of China＇s gross domestic product （GDP）. China＇s GDP loss estimated by the general equilibrium approach reached 0.38‰ （ranging from 0.16‰ to 0.51‰）. The difference between the two approaches and the implications of the results were discussed.

Experimental study of the critical sand starting velocity of gas-watersand flow in an inclined pipe

The purpose of this paper is to study the critical sand starting velocity and transformation law of flow pattern based on gas-water-sand three-phase flow in an inclined pipe.Firstly,the indoor simulation experiment system of gas-water-sand three-phase flow was used to test the conversion law of flow pattern based upon the different gas void fraction.Secondly,the influence of slug bubbles on sand migration was investigated according to distinctive hole deviation angles,gas void fraction and sand concentration.Finally,the critical sand starting velocity was tested based on dissimilar hole deviation angles,gas void fraction,sand concentration and sand particle size,and then the influence of the abovementioned key parameters on the sand starting velocity was debated based on the force analysis of the sand particles.The experimental results illustrated that when the gas void fraction was less than 5%,it was bubbly flow.When it increased from 5%to 30%,the bubbly flow and slug flow coexisted.When it was between 30%and 50%,the slug flow and agitated flow coexisted.When it reached 50%,it was agitated flow.Providing that the hole deviation angle was 90°,the phenomenon of overall migration and wavelike migration on the surface of sand bed was observed.On the contrary,the phenomenon of rolling and jumping migration was recognized.The critical sand starting velocity was positively correlated with the hole deviation angle and sand particle size,but negatively associated with the gas void fraction and sand concentration.This research can provide a certain reference for sand-starting production in the field of petroleum engineering.

A particle-linkage model for non-axisymmetric elongated asteroids

This paper investigates a simplified model for describing the gravitational fields of non- axisymmetric elongated asteroids. The connection between the simplified model and the target aster-oid is built by considering the positions of equilibrium points. To improve the performance of po-sition matching for the equilibrium points associated with these non-axisymmetric asteroids, a non-axisymmetric triple-particle-linkage model is proposed based on two existing axisymmetric particle- linkage models. The unknown parameters of the simplified model are determined by minimizing the matching error using the nonlinear optimization method. The proposed simplified model is applied for three realistic elongated asteroids, 243 Ida, 433 Eros and （8567） 1996 HW1. The simulation re-sults verify that the current particle-linkage model has better matching accuracy than the two existing particle-linkage models. The comparison, between the simplified model and the polyhedral model, on the topological cases of the equilibrium points and the distribution of gravitational potential further validate the rationality and accuracy of the simplified model.

Considerations in Applying the General Equilibrium Approach to Environmental Health Assessment

There are currently two commonly used approaches to assessing economic impacts of health damage resulting from environmental pollution： human capital approach （HCA） and willingness-to-pay （WTP）. WTP can be further divided into averted expenditure approach （AEA）, hedonlc wage approach （HWA）, contingent valuation approach （CVA） and hedonlc price approach （HPA）. A general review of the principles behind these approaches by the authors indicates that these methods are incapable of unveiling the mechanism of health impact from the point of view of national economy. On a basis of economic system, the shocks brought about by health effects of environmental pollution change the labor supply and medical expenditure, which in turn affects the level of production activity in each sector and the total final consumption pattern of the society. The general equilibrium approach within the framework of macroeconomic theory is able to estimate the health impact on national economy comprehensively and objectively. Its mechanism and applicability are discussed in detail by the authors.

A dynamic managed pressure well-control method for rapid treatment of gas kick in deepwater managed pressure drilling

During deepwater managed pressure drilling(MPD),the gas kick may occur in abnormally high-pressure formations.If the traditional well control method is adopted,the treatment time is long and the advantage of early gas kick detection of MPD is lost.The dynamic managed pressure well-control(MPWC)method can be used to rapidly treat gas kick in deepwater MPD.In this paper,considering the effect of large-variable-diameter annulus and complex wellbore temperature in deepwater drilling,a simplified model of non-isothermal gas-liquid two-phase flow was established for dynamic deepwater MPWC simulation.Using this model,the response characteristics of outlet flow and wellhead backpressure were investigated.The results indicated that the gas fraction,outlet liquid flow rate,pit gain and wellhead backpressure presented complex alternating characteristics when gas moved upwards in the wellbore due to the large-variable-diameter annulus.The outlet liquid flow rate would be lower than the inlet flow rate and the pit gain would decrease before the gas moved to the wellhead.The variation trend of the wellhead backpressure was consistent with that of the pit gain.When the gas-liquid mixture passed through the choke,the expansion or compression of the gas caused part of the choke pressure drop to be supplemented or unloaded,delaying the response rate of the wellhead backpressure.The wellbore temperature,borehole diameter and seawater depth had different effects on outlet flow rate,pit gain and wellhead backpressure.This research could provide a new idea for well control methods in deepwater managed pressure drilling.

Feasible region and stability analysis for hovering around elongated asteroids with low thrust

This paper investigates properties of low-thrust hovering, including the feasible region and stability, in terms of the dynamical parameters for elongated asteroids. An approximate rotating mass dipole model, by which the description of the rotational gravitational field is reduced to two independent parameters, is employed to construct normalized dynamical equations. The boundaries of the feasible region are determined by contours representing the magnitude of the active control. The effects of a rotating gravitational field and maximal magnitude of the low thrust on the feasible hovering regions are analyzed with numerical results. The stability conditions are derived according to the forms of the eigenvalues of the linearized equation near the hovering position. The stable regions are then determined by a grid search and the effects of the relevant parameters are analyzed in a parametric way. The results show that a close hovering can be easier to realize near the middle of the asteroid than near the two ends in the sense of both required control magnitude and stability.

CTGFsiRNA ameliorates retinal cells apoptosis in streptozotocin-induced diabetic rats

AIMTo detect the effect of connective tissue growth factor (CTGF) on the apoptosis in the diabetic retina with small interfering RNAs (siRNA) targeting CTGF.

The impact of chemotherapy on cognitive function of breast cancer patient

Objective:Chemotherapy significantly improved the survival of breast cancer,but also brings various symptoms and psychological distresses.Cognitive dysfunction was usually ignored.This study aimed to investigate the changes in cognitive function during chemotherapy and its influence on the quality of life in breast cancer patients.Methods:Female patients with newly diagnosed breast cancer have prospectively enrolled in this study.Participants investigated and completed questionnaires at four-time points:pre-chemotherapy(T1),post-chemotherapy(T2),6 months(T3)and 12 months(T4)after the completion of chemotherapy.The Functional Assessment of Cancer Therapy-Cognitive scale and the Functional Assessment of Cancer Therapy-Breast Cancer scale used was to assess the cognitive function and the quality of life,respectively.Data were analyzed using descriptive and repeated-measures analysis of variance statistics.Results:One hundred and eighty-three patients participated in the study and completed questionnaires at least 2 times.The mean score of cognitive function and the quality of life were significantly different at a different time point(P<0.05 for all).The trends of cognitive scores shown that the most serious damage of cognitive function appeared after beginning chemotherapy and followed by a slowly turn back after the completion of chemotherapy.The trend of the mean score of the quality of life after chemotherapy was similar to that of the cognitive score.The degree of cognitive dysfunction was significantly associated with the score of the quality of life at each time point after chemotherapy(P<0.05).Conclusion:Chemotherapy is closely associated with a cognitive impairment,which contributes to a significant decrease in the quality of life of patients with breast cancer.

Fast three-dimensional radiation field characterization in largescale nuclear installations

The requirement of the fast three-dimensional radiation field calculation is raised during the decommissioning of large-scale nuclear installations. The most often used methods, such as the Monte Carlo and the discrete ordinates methods, have shortcomings in their simulations of such problems. The coupled Monte Carlo–point kernel computational scheme is developed to meet the requirement. The facility is separated into the source region and the bulk shielding region, with a common interface. The transport within the source region is simulated using the Monte Carlo method, which is by nature good at treating complex geometries. The radiation field in the bulk shielding region is treated by the point kernel approach to avoid the extremely expensive computation for deep penetration problems. The flow rate through the interface,which is given by the Monte Carlo simulation, is considered as the equivalent surface source for the point kernel calculation. Test calculations from simplified typical waste storage facilities have been performed to validate the coupled scheme by comparing them with the results conducted by the Monte Carlo method directly. The good agreement of the results, as well as the significant saving in computing time, indicates that the coupled method is suitable for the fast three-dimensional radiation field calculation.

Effects of solar radiation pressure on asteroid surface hopping transfers for high area/mass ratio rovers

The high area/mass ratio hopping rovers have potential applications in future asteroid surface exploration.This paper systematically investigates the effects of solar radiation pressure(SRP)on ballistic surface hopping transfers for the asteroid 101955 Bennu.Effects of SRP on the traveled distance and the trajectory design of hopping transfers are analyzed and summarized.The simulation results indicate that it is necessary to take SRP into account to ensure the success of hopping transfers and the proper use of SRP can help design the trajectories of hopping transfers with low initial impulses and short transfer times.It also reveals the potential possibility in using SRP to control the post-hopping transfers with specific control policies in the future surface exploration of asteroids.

Analysis of the rogue waves in the blood based on the high-order NLS equations with variable coefficients

The research of rogue waves is an advanced field which has important practical and theoretical significances in mathematics,physics,biological fluid mechanics,oceanography,etc.Using the reductive perturbation theory and long wave approximation,the equations governing the movement of blood vessel walls and the flow of blood are transformed into high-order nonlinear Schrodinger(NLS)equations with variable coefficients.The third-order nonlinear Schrodinger equation is degenerated into a completely integrable Sasa–Satsuma equation(SSE)whose solutions can be used to approximately simulate the real rogue waves in the vessels.For the first time,we discuss the conditions for generating rogue waves in the blood vessels and effects of some physiological parameters on the rogue waves.Based on the traveling wave solutions of the fourth-order nonlinear Schrodinger equation,we analyze the effects of the higher order terms and the initial deformations of the blood vessel on the wave propagation and the displacement of the tube wall.Our results reveal that the amplitude of the rogue waves are proportional to the initial stretching ratio of the tube.The high-order nonlinear and dispersion terms lead to the distortion of the wave,while the initial deformation of the tube wall will influence the wave amplitude and wave steepness.

The (3+1)-dimensional generalized mKdV-ZK equation for ion-acoustic waves in quantum plasmas as well as its non-resonant multiwave solution

The quantum hydrodynamic model for ion-acoustic waves in plasmas is studied.First,we design a new disturbance expansion to describe the ion fluid velocity and electric field potential.It should be emphasized that the piecewise function perturbation form is new with great difference from the previous perturbation.Then,based on the piecewise function perturbation,a(3+1)-dimensional generalized modified Korteweg–de Vries Zakharov–Kuznetsov(mKdV-ZK)equation is derived for the first time,which is an extended form of the classical mKdV equation and the ZK equation.The(3+1)-dimensional generalized time-space fractional mKdV-ZK equation is constructed using the semi-inverse method and the fractional variational principle.Obviously,it is more accurate to depict some complex plasma processes and phenomena.Further,the conservation laws of the generalized time-space fractional mKdV-ZK equation are discussed.Finally,using the multi-exponential function method,the non-resonant multiwave solutions are constructed,and the characteristics of ion-acoustic waves are well described.

The prognostic value of baseline circulating tumor cells in patients with metastatic breast cancer: a meta-analysis

Objective:The prognostic value of circulating tumor cells(CTCs)in metastatic breast cancer(MBC)patients was contentious.A meta-analysis was conducted to evaluate whether MBC patients’clinical outcomes could be predicted by CTCs detection.Methods:Relevant published studies were searched through electronic databases from January 1990 to February 2018,among which,those investigated the correlation between CTCs and clinical outcomes of progression-free survival and overall survival in MBC patients were involved.The hazard ratios(HR)and confidence intervals(CI)in the studies were extracted from the study using random or fixed effects model,and the meta-analysis was conducted.The prognostic value of tumor cells in patients with different subtypes was estimated by subgroup analysis.Results:Twenty-one eligible studies enrolling 3,837 patients were appropriate for pooled analysis.Progression-free survival(HR,1.66;95%CI,1.47–1.87;P=0.000)and overall survival(HR,2.51;95%CI,2.13–2.96;P=0.000)were worse in patients with CTCs-positive.Subtypes of hormone receptor(HorR)positive,human epidermal growth factor receptor-2(HER2)negative and triple negative with presence of CTCs showed a statistically significant worse PFS and OS.However,CTCs detection presented no prognostic value in patients with HorR-negative or HER2-positive subtypes.Conclusion:The enumeration of CTCs at baseline in patients with MBC subtypes of HorR-positive,HER2-negative and triple negative is connected with disease progression and poor survival,but inappropriate for HorR-negative and HER2-positive subtypes.

Pichia pastoris composition expressed aerolysin mutant of Aeromonas veronii as an oral vaccine evaluated in zebrafish(Danio rerio)

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture.In this study,virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen.Pichia pastoris constitutive secretory expression NTaer(GS115-NTaer)was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity.The result shows that vaccination of GS115-NTaer for four weeks did not affect the growth performance of the host,while eliciting an effective immune protective response.Compared with the control group,the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α(TJP1α)gene,and significantly increased the contents of lysozyme(LYZ),complement C3 and C4 in the gut,indicating that the innate immune response of the fish was activated.The relative gene expression levels of macrophage-expressed gene 1(MPEG1)and T cell receptor(TCR-α)in the gut,and MPEG1,CD4,CD8,TCR-α,GATA3,and T-bet in the spleen were all increased significantly,indicating that the cellular immune response of the fish was activated.Furthermore,the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased,which showed that humoral immunity was also activated.Moreover,inoculation with GS115-NTaer significantly changed the structure of gut microbiota.In particular,the relative ratio of(Firmicutes+Fusobacteriota+Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups.Lastly,the vaccinated fish were challenged with A.veronii,and the relative percent survival of GS115 and the GS115-NTear groups was 14.28%and 33.43%.This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model.Collectively,this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A.veronii infection in fish aquaculture.