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Amu Darya Basin is an important gas-rich basin in Central Asia. In recent years, some small-sized and sporadically-distributed oil reservoirs have been discovered in this basin during exploration of pre-salt gas. However, the oil reservoir-forming conditions, distribution and size of these oil reservoirs are not clear, which brings troubles to exploration and development. The tectonic evolution, geochemical analysis, oil-source rock correlation and the simulation & analysis of hydrocarbon generation from source rocks made for the framework cross-section in the Amu Darya Right Bank have revealed that: 1) There are three sets of source rocks, including the Lower-to-Middle Jurassic coal-bearing strata, Upper Jurassic marlstones and mudstones, and crude oil mainly comes from the Upper Jurassic mudstones; 2) The Lower-to-Middle Jurassic coal-bearing source rocks, which matured at the beginning of Early Cretaceous and entered the peak hydrocarbon generation stage at the beginning of Late Cretaceous, are now mainly in the stage of wet gas and dry gas; whilst the Middle-to-Upper Jurassic marlstones and mudstones, which matured at the end of Early Cretaceous and entered the peak hydrocarbon generation stage at the end of Late Cretaceous, are now mainly in the stage of oil generation window; 3) At the beginning of Late Cretaceous, hydrocarbon accumulations were formed in pre-salt reef and shoal traps and low-amplitude inherited uplifts, and pre-salt thrust structures of Paleogene age began to develop. The Lower-to-Middle Jurassic natural gas migrated to carbonate rocks on a large scale, and the natural gas expelled crude oil that accumulated earlier to form gas reservoirs. Gas-cap oil reservoirs were formed as some crude oil was not completely expelled; 4) The development of paleo-traps in the early period and the weak expulsion of natural gas in the late period are important conditions for the formation of oil reservoirs. The areas featured by a paleo-uplift setting in the early stage and now located in a sag zone are the plays for development of oil reservoirs, which are dominated by small-sized oil reservoirs and limited in overall size of resources.

Multiple hot-compression tests were carried out on the 6082 aluminum (Al) alloy using a Gleeble-1500 thermal simulation testing machine. Data on flow stresses of the 6082 Al alloy at deformation temperatures of 623 to 773 K and strain rates from 0.01 to 5 s&minus, 1 were attained. Utilizing electron backscatter diffraction (EBSD) and a transmission electron microscope (TEM), the dynamic recrystallization behaviors of the 6082 Al alloy during hot compression in isothermal conditions were explored. With the test data, a hot-working processing map for the 6082 Al alloy (based on dynamic material modeling (DMM)) was drawn. Using the work-hardening rate, the initial critical strain causing dynamic recrystallization was determined, and an equation for the critical strain was constructed. A dynamic model for the dynamic recrystallization of the 6082 Al alloy was established using analyses and test results from the EBSD. The results showed that the safe processing zone (with a high efficiency of power dissipation) mainly corresponded to a zone with deformation temperatures of 703 to 763 K and strain rates of 0.1 to 0.3 s&minus, 1. The alloy was mainly subjected to continuous dynamic recrystallization in the formation of the zone. According to the hot-working processing map and an analysis of the microstructures, it is advised that the following technological parameters be selected for the 6082 Al alloy during hot-forming: a range of temperatures between 713 and 753 K and strain rates between 0.1 and 0.2 s&minus, 1.

It is taken as a novel prospective process to treat iron concentrate from hydrometallurgical zinc kiln slag for comprehensive utilization of valuable metals by a hydrochloric acid leaching-spray pyrolysis method. The leaching mechanism of different valuable metals was studied. The results revealed that the leaching rates of Ag, Pb, Cu, Fe, As and Zn were 99.91%, 99.25%, 95.12%, 90.15%, 87.58% and 58.15%, respectively with 6 mol/L HCl and L/S ratio of 10:1 at 60 °C for 120 min. The action of SiO2 in leaching solution was also studied. The results showed that the precipitation and settlement of SiO2(amorphous) adsorbed part of metal ions in solution, which greatly inhibited the leaching of Cu, Fe, As and Zn, so it is crucial to control the precipitation of amorphous SiO2.

Based on the empirical electronic theory of solids and molecules (EET), the actual model for unit cell of cementite (θ-Fe3C) was built and the valence electron structures (VES) of cementite with specified site and a number of Fe atoms substituted by alloying atoms of M ( M=Cr, V, W, Mo, Mn ) were computed by statistical method. By defining P as the stability factor, the stability of alloyed cementite with different numbers and sites of Fe atoms substituted by M was calculated. Calculation results show that the density of lattice electrons, the symmetry of distribution of covalent electron pairs and bond energy have huge influence on the stability of alloyed cementite. It is more stable as M substitutes for Fe2 than for Fe1. The alloyed cementite is the most stable when Cr, Mo, W and V substitute for 2 atoms of Fe2 at the sites of Nos. 2 and 3 (or No. 6 and No. 7). The stability of alloyed cementite decreases gradually as being substitutional doped by W, Cr, V, Mo and Mn.

Brucella spp. is the causative agent of brucellosis, an extremely important disease worldwide. Innate immune cells detect pathogens via repeated cellular patterns (PAMPs) such as the Brucella suis (B. suis) lipopolysaccharide (LPS) coat on Gram-negative bacteria, which act as an important virulence factor of Brucella. B.suis LPS may be an issue for pro-inflammatory cytokine induction such as interleukin-1 (IL-1), interleukin-18 (IL-18) and interleukin-1â (IL-1â), which released from immune cells to mediate downstream inflammatory effects. To elucidate the mechanism of how B.suis LPS affects the secretion of IL-1, IL-18 and IL-1â in macrophages. We identified the up-regulation of caspase-11 in a porcine alveolar macrophages (PAM) cells stimulated with B.suis LPS. Furthermore, specific small interfering RNA (siRNA) targeting caspase-11 effectively inhibited B.suis LPS stimulated IL-1, IL-18 and IL-1â release from PAM. The results indicated that the concentrations of IL-1, IL-18 and IL-1â of caspase-11 siRNA pretreated group were lower than that of control significantly. Caspase-11 plays an important role in IL-1, IL-18 and IL-1â secretion from porcine alveolar macrophage cells stimulated with Brucella suis LPS, and these findings might aid our understanding of the pathogenic mechanisms of Brucella and provide an entirely new innate immune response mechanism underlying macrophages dysfunction during Brucella infection.

Wave velocities in haloanhydrites are difficult to determine and significantly depend on the mineralogy. We used petrophysical parameters to study the wave velocity in haloanhydrites in the Amur Darya Basin and constructed a template of the relation between haloanhydrite mineralogy (anhydrite, salt, mudstone, and pore water) and wave velocities. We used the relation between the P-wave moduli ratio and porosity as constraint and constructed a graphical model (petrophysical template) for the relation between wave velocity, mineral content and porosity. We tested the graphical model using rock core and well logging data.

The carbon nanotubes (CNTs) modified by the carbon particles with diameter of 120-180 nm are prepared by using hydrocarbon ion deposition techniques. Based on the investigation of scanning electron microscopy and transmission electron microscopy, the CNTs are decorated by some nanospheres with size of 120-180 nm randomly, and the full CNTs surface besides the area of nanosphere is coated by the graphene stacks with size of 10-15 nm. The nanospheres are composed of several nanoparticles of graphene stacks and are seamless connected with graphene stacks. The sparse distribution CNTs on Si substrate is crucial for the formation of carbon nanospheres. The formation of carbon nanospheres proceeds through the following three stages: the formation of graphene nanoparticle on CNTs surface and silicon substrate – the migration of active hydrocarbon groups towards the surface of the CNTs deposition zone at high temperature – the formation of carbon nanospheres by the aggregating hydrocarbon active groups.

Prolonged exposure to opiates induces a constellation of neuroadaptations, especially in the mesolimbic dopamine system (MLDS), which leads to alteration in the function of motivational circuitry. The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and plays an important role in processes associated with neural plasticity. Moreover, it has been shown that NCAM were related to risk of alcoholism in human populations. Here, coimmunoprecipitation and western blotting were used to investigate whether morphine treatment induced alteration of the expression of NCAM or its signaling level in MLDS. The rats receiving escalating dose of morphine treatment were divided into three groups: morphine 1d, 3d and 5d group, which were injected subcutaneously with morphine hydrochloride for 1 day, 3 days and 5 days, respectively. Twelve hours after the last injection, animals were sacrificed and the tissues of ventral tegmental area (VTA), prefrontal cortex (PFC) and nucleus accumbens (NAc) were punched out to examine the expression of NCAM or its signaling level. The results showed that morphine treatment had no significant effect on the expression of NCAM, but downregulated the phosphorylation of NCAM-associated focal adhesion kinase (FAK) in the VTA and PFC of rats. In the NAc of rats, however, the expression of NCAM and its signaling were not altered significantly by morphine treatment. These results indicated that the downregulation of NCAM signaling in the VTA and PFC might be involved in the formation of morphine addiction.

Commercial grade-70 tire cord steel was microalloyed with V and N to explore the possibility of substituting V for C and the effect of V and N on cementite dissolution during cold drawing process. Tensile strength, elongation and torsion laps of cold-drawn wires were determined. Microstructures of secondary phases were studied by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Saturation magnetization was measured by using a vibrating sample magnetometer (VSM) to evaluate cementite dissolution during cold drawing process. Experimental results showed that with the increase of V content, tensile strength increased, elongation slightly decreased, and the torsion laps of the cold-drawn wires decreased. Results also showed that with the increase of N content, a peak (increasing first and then decreasing) appeared in the tensile strength graph, and an increase of elongation and a decrease of torsion laps of the cold-drawn wires occured. N is soluble in ferrite when its content is low. The increase in the content of N to 82 × 10 −6 will result in the precipitation of the V-containing secondary phases. Also, cementite tended to be stable during cold drawing process with the increase of V and N contents. Grade-80 tire cord steel can be replaced by grade-70 tire cord steel microalloyed with 0.086 mass% V.

Facile intramolecular N2-arylation catalyzed by CuI/ l -proline has been developed to prepare in good to excellent yields a variety of benzo[ f ]pyrazolo[1,5- a ][1,4]diazepin-4-ones and previously unreported benzo[6,7][1,4]diazepino[1,2- b ]indazol-7(6 H )-ones.

Treatment of neuropathic pain (NP) continues to be a clinical challenge and the underlying mechanisms of NP remain elusive. More evidence suggests that glial cell line-derived neurotrophic factor (GDNF) has potent anti-nociceptive effects on NP, but the underlying mechanisms are still largely unknown. Recent data have shown that integrin β1 plays an important part in NP induction, and that the activity of integrin β1 signaling is associated with the phosphorylation of the conserved threonines in the cytoplasmic domain and recruitment of focal adhesion kinase (FAK) to the integrin β1 tail and phosphorylation. We assessed the effect of GDNF on integrinβ1/FAK signaling in NP states. Immunostaining results showed that integrin β1 was mainly observed in the superficial dorsal horn in the spinal cord of rats, and was mostly expressed in intrinsic neurons. Expression of p-integrin β1 and the phosphorylation of integrin β1-associated FAK, but not integrin β1 itself, was up-regulated after chronic constriction injury (CCI), which could be reversed by GDNF, and the effect of GDNF on integrin β1/FAK signaling was inhibited by pre-treatment with RET function-blocking antibody (RET Ab). Moreover, pre-treatment with RET Ab could antagonize the effect of GDNF on inhibiting the NP induced by CCI. These data suggest that GDNF can regulate integrin β1 activity via a RET-related mechanism.

In this article, we studied the structural properties and electrical characteristics of GdTiO3 gate dielectric for amorphous indium–gallium–zinc oxide (a-IGZO) thin-film transistor (TFT) applications. The a-IGZO TFT device featuring the GdTiO3 gate dielectric exhibited better electrical characteristics, including a small threshold voltage of 0.14 V, a large field-effect mobility of 32.3 cm2/V-s, a high Ion/Ioff current ratio of 4.2 × 108, and a low subthreshold swing of 213 mV/decade. Furthermore, the electrical instability of GdTiO3 a-IGZO TFTs was investigated under both positive gate-bias stress (PGBS) and negative gate-bias stress (NGBS) conditions. The electron charge trapping in the gate dielectric dominates the PGBS degradation, while the oxygen vacancies control the NGBS degradation.

This paper introduces the characteristics and distribution of sulfide ore cassiterite, an overview of the re-election of sulfide ore cassiterite flotation basic skills and status, and the use of tin resources and sorting technology development proposed sulfide ore cassiterite Prospect.

This paper introduces the research on the beneficiation of a low-grade barite ore taken from Myanmar.Through the analysis of the ore properties and research on the flotation experiment, the optimum flotation conditions are determinedwhile the ore sample assays 64.32% BaSO4.Under the flotation conditions of the grinding fineness-200 meshes 80%, sodium oleate 800g / t and sodium silicate 500 g / t, “two-time roughing,one closed cleaningand open in the second cleaning operations” is applied, and two marketable barite concentrates can be obtained. The concentrate 1 and 2 contain 96.32% and 91.26%BaSO4 at the recoveries of 91.94% and 5.25%, respectively.

Heading date is a key determinant of regional and seasonal adaptation in rice (Oryza sativa L.). A minor-effect quantitative trait locus (QTL), QTL for D ays t o h eading 12a (qDTH-12a), with unknown genetic action was previously coarsely detected in a recombinant inbred line population. The study reported here was designed to better define the qDTH-12a locus (designated as DTH12) in advanced segregating populations. DTH12 was initially verified in chromosome segment substitution line CSSL84. A CSSL84/Asominori//Asominori BC4F2 population was then developed, and a near-isogenic line (NIL), NIL(DTH12), was subsequently selected from this population using marker-assisted tracking that headed 8 days later than Asominori under long-day (LD) conditions but which was not significantly different in heading date in short-day environments. Using 358 Asominori/NIL(DTH12) F2:3 families grown under LD conditions, we were able to initially map DTH12 to a 26-cM interval between markers InDel12-1 and RM6296. F3 individuals heterozygous for the DTH12 regions were then chosen, and 2,388 F4:5 families were used for fine mapping. DTH12 was finally dissected as a single gene and delimited to a 153-kb genomic region with 32 open reading frames. Compared with Asominori, NIL(DTH12) showed reduced transcription of the florigen genes Heading date 3a and RICE FLOWERING LOCUS T 1, suggesting that DTH12 functions as an up-regulator of florigen genes during floral induction under LD conditions. DTH12 was also found to have an important role in rice adaptation and breeding for precise control of seed maturity. These findings provide a firm basis for cloning this minor-effect QTL involved in rice flowering.

Feizhu powder, which is a classical Chinese medicine prescription collected in the Chinese Veterinary Pharmacopoeia, comprises four kinds of Chinese herbs: Rhizoma dryopteridis crassirhizomatis, Radix polygoni multiflori (prepared), Fructus hordei germinatus and Soybean (fry). According to dose proportion in the prescription and preparation method collected in the Chinese Veterinary Pharmacopoeia, we have prepared the Feizhu powder. In order to research the antibacterial activity in vitro of homemade Feizhu powder, it was extracted with 95% ethanol and water, respectively. Then minimum inhibitory concentration (MIC) of the extract was detected against Streptococcus suis, Staphylococcus aureus and Escherichia coli by micro porous-plate method. The results showed that MICs of Feizhu powder water extract ranged from 250 mg/mL to 500 mg/mL. While MICs of Feizhu powder alcohol extract ranged from 31.25 mg/mL to 62.5 mg/mL. The test data indicated that antimicrobial activity of Feizhu powder alcohol extract is superior to that of water extract, this lay the foundation for the extract of the antibacterial active ingredients and further research on Feizhu powder.

Bangduling (BDL) oral liquid, which is a new research and development herbal preparation, comprises four traditional Chinese medicines (TCM): Radix Scutellariae, Cortex Phellodendri Chinensis, Folium Isatidis, and Radix et Rhizoma Rhei. A simple, reliable and reproducible method, based on a high performance liquid chromatography-diode array detector (HPLC-DAD) method, for establishing fingerprint of complex herbal medicine BDL oral liquid was described firstly. In order to develop and validate this HPLC-DAD method, Kromasil C18 column (S-5μm, 4.6 mm × 250 mm) was used with gradient mobile phase at the column temperature of 30°C. The mobile phase was consisted of methanol and water containing 0.1% phosphoric acid. UV wavelength was set at 254 nm. Ten batches of BDL preparations were used to establish the HPLC fingerprint. In addition, the contents of baicalin in the preparations were also determined. Validation of the analytic method was evaluated by stability, precision and repeatability test. Calibration curve for baicalin showed good linearity with R2 = 0.9992. The relative standard deviations (RSDs) value of the relative retention time and peak area in the stability, precision and repeatability test, were less than 1% and 5%, respectively. The similarity of 10 batches of BDL oral liquid was more than 0.958, which showed the preparations from different batch productions were consistent. This established determination method could be efficient to the quality control of BDL oral liquid.

Response surface methodology (RSM) and single factor test were used to optimize preparation technology on medicated serum of Yinqiaotiangan (YQTG) in mice. The influent factors of preparing medicated serum include blood sampling time, administration times, and administration dosage. The content of chlorogenic acid in medicated serum was detected by high performance liquid chromatography (HPLC). Results showed that the optimum preparation technology of medicated serum is 33 minutes of blood sampling time, 4 times of administration times and 0.024g/mL of administration concentration. Under this condition, the concentration of chlorogenic acid reached peak 33.34 μg/mL in mice medicated serum. It is seen that the RSM method effectively and accurately optimize preparation technology on medicated serum of YQTG preparation.

The possible molecular geometries of 134 halogenated methyl-phenyl ethers were optimized at B3LYP/6-31G * level with Gaussian 98 program. The calculated structural parameters were taken as theoretical descriptors to establish two new novel QSPR models for predicting aqueous solubility (−lg S w,l ) and n -octanol/water partition coefficient (lg K ow ) of halogenated methyl-phenyl ethers. The two models achieved in this work both contain three variables: energy of the lowest unoccupied molecular orbital ( E LUMO ), most positive atomic partial charge in molecule ( q + ), and quadrupole moment ( Q yy or Q zz ), of which R values are 0.992 and 0.970 respectively, their standard errors of estimate in modeling (SD) are 0.132 and 0.178, respectively. The results of leave-one-out (LOO) cross-validation for training set and validation with external test sets both show that the models obtained exhibited optimum stability and good predictive power. We suggests that two QSPR models derived here can be used to predict S w,l and K ow accurately for non-tested halogenated methyl-phenyl ethers congeners.

Milling process of jointing blank of 7022 aluminum alloy was simulated by ANSYS. The results show that the maximum residual tensile stress and pressure stress are mainly concentrated in the jointing seam zone when the jointing blank is milled. The milling deformation of jointing blank is shown as “wave” shape. The milling deformation of key eye side is shown upwarp. The jointing initiating terminal is shown downward displacement. The maximum downward displacement is present to the middle of jointing seam central line. In additional, the milling deformation along sheet length direction is shown outward extension.

Silibinin was reported to have high cyto-toxicity in many malignant cell lines, however, it showed low cyto-toxicity in treatment of human melanoma A375-S2 cells and even protected these cells against certain stress insults. Reactive oxygen species was reported to have controversial effects on cancer chemotherapy. In this study we investigated the mechanism of reactive oxygen species generation and the role of reactive oxygen species in protecting cells against silibinin induced cyto-toxicity in A375-S2 cells. We found that silibinin induced the generation of large amount of superoxide anion (O 2 ∙− ) and small amount of hydrogen peroxide (H 2 O 2 ) through down-regulating the activity of mitochondrial complex IV and the protein level of cytochrome c . We also discovered that O 2 ∙− generation activated insulin like growth factor-1 receptor (IGF-1R) and its down-stream phosphatidylinositol 3-kinases–Akt (PI3K–Akt) and phospholipase C γ–protein kinase C (PLC γ–PKC) signaling pathways, which were augmented by H 2 O 2 scavenger catalase. Scavenging O 2 ∙− by superoxide dismutase (SOD) or inhibition of IGF-1R-PI3K–Akt and IGF-1R-PLC γ–PKC signaling pathways increased cell apoptosis. Therefore, O 2 ∙− mediated cell resistance to silibinin via activating IGF-1R-PI3K–Akt and IGF-1R–PLC γ–PKC pathways in silibinin treated A375-S2 cells.

A three-step method was developed to convert N-1 unprotected 3-substituted indoles to 3-substituted 2-acylaminoindoles. Established indole chlorination chemistry was employed to generate stable 2-trifluoroacetylamino indoles, which were subsequently deprotected and selectively acylated.

Beneficiation of a low-grade barite ore assaying 64.32% BaSO4 was conducted by flotation using sodium oleate and sodium silicate. The effect of grinding fineness, type and dosage of flotation reagent in roughing were investigated. Based on the optimum flotation conditions, a close circuit flowsheet was established. Finally, two barite concentrates assaying 96.32% and 91.26% BaSO4 can be obtained at the recovery of 91.94% and 5.25%, respectively, by applying two-time roughing and two-time cleaning operations.

Irritable bowel syndrome is a disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that stressors presented during gestational periods could have long-term effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. The aim of the present study is to determine whether prenatal maternal stressis a adverse factor affecting gastrointestinal sensitivity and to investigate possible mechanisms underlying prenatal maternal stress-induced visceral hypersensitivity in adult offspring. Prenatal maternal stress was induced in pregnant Sprague-Dawley rats by exposure to heterotypic intermitent stress from gestational day 7 to delivery. Prenatal maternal stress significantly increased visceromotor response to colorectal distention in adult offspring from the age of 6 weeks to 10 weeks. Prenatal maternal stress also enhanced neuronal excitability including depolarization of resting membrane potentials, reduction in rheobase, and an increase in the number of action potentials evoked by 2× and 3× rheobase current stimultion of colon-specific dorsal root ganglion neurons. Prenatal maternal stress remarkably enhanced expression of cystathionine-β-synthase and Nav1.7 in T13-L2 thoracolumbar dorsal root ganglions both at protein and mRNA levels. Intraperitoneal injection of aminooxyacetic acid, an inhibitor of cystathionine-β-synthase, attenuated prenatal maternal stress-induced visceral hypersensitivity in a dose-dependent manner. A consecutive seven-day administration of aminooxyacetic acid reversed the hyperexcitability of colon-specific dorsal root ganglion neurons and markedly reduced Nav1.7 expression. These results indicate that the presence of multiple psychophysical stressors during pregnancy is associated with visceral hypersensitivity in offspring, which is likely mediated by an upregualtion of cystathionine-β-synthase and Nav1.7 expression. Prenatal maternal stress might be a significant contributor to irritable bowel syndrome, and cystathionine-β-synthase might be a potential target for treatment for chronic visceral hypersensitivity in patients with irritable bowel syndrome.

Increasing research has concentrated on the anti-tumour efficacy of silibinin, a flavonolignan that is clinically used as an hepatoprotectant. However, previous work has found that silibinin-induced apoptosis is accompanied by protective superoxide (O(2)*-) generation in MCF-7 cells. This study further reports the formation of reactive nitrogen species (RNS) in the same system. It finds that silibinin induces nitric oxide (*NO) generation in a time- and concentration-dependent manner. Moreover, the results support that there exists an inter-regulation pattern between RNS and reactive oxygen species (ROS) generation. In addition, silibinin is also found to induce RNS and ROS generation in the isolated populations of mouse peripheral blood mononuclear cells (PBMCs) and a simple in vivo model of Caenorhabditis elegans.

A series of α,α-disubstituted amines have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic, and heteroaromatic nitriles. Key to this reported procedure is the unprecedented addition of the Grignard reagent to the nitrile under heating by microwave irradiation which both significantly improves reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5–10 min at 100 °C followed by rapid reduction with sodium borohydride to give the target amines.

A highly efficient procedure was developed for the microwave-assisted synthesis of N-heteroaryl-4-(2-chloroethyl)piperazines and N-heteroaryl-4-(2-chloroethyl)piperidines. Microwave irradiation of electron deficient heteroaryl chlorides with 1,4-diazabicyclo[2.2.2]octane (DABCO) at 160 degrees C for 15 min led to N-heteroaryl-4-(2-chloroethyl)piperazines in good to excellent yields. In a similar manner, microwave irradiation of electron deficient heteroaryl chlorides with quinuclidine at 180 degrees C for 15 min provided N-heteroaryl-4-(2-chloroethyl)piperidines in good to excellent yields. Extension of the method was demonstrated by the development of a one-pot, two-step microwave-assisted protocol for the synthesis of 4-(2-acetoxyethyl)-substituted N-heteroarylpiperazines and N-heteroarylpiperidines to demonstrate the production of a small library in a parallel fashion.

The mathematic model was established between finished surface residual stress and milling parameters by orthogonal regression testing. The rationality of the model was certified by FEM and test. The simulation hypothesis and process were verified by the model. The test showed that the model and FEM were feasible.

Silibinin is known for its hepatoprotective, anti-inflammatory, and anti-carcinogenic effects. We found that silibinin exhibited a protective effect against chemotherapeutic reagent mitomycin C–induced cell death in A375-S2 cells in a p53-dependent manner, which contradicted the findings of previous studies investigating the anti-neoplastic activity of silibinin and developing silibinin as a potential anti-neoplastic drug in clinical therapy. Mitomycin C administration triggered a time- and dose-dependent cell death in A375-S2 cells. Apoptotic morphology, DNA fragmentation, and caspase-3 activation demonstrated that the major cause of A375-S2 cell death by mitomycin C was apoptosis. This was associated with a marked increase of p53 level and changes in mitochondria associated proteins. However, preincubation with silibinin prior to mitomycin C treatment substantially suppressed cell apoptosis, attenuated the change of p53 and Bcl-2 expressions, blocked the translocation of Bax to mitochondrial outer membrane, and ameliorated the loss of mitochondrial membrane potential, but mitomycin C stimuli led to few changes in the protein levels of caspase 8, Fas ligand, and Fas-associated death domain protein, indicating that silibinin protected cells from mitomycin C–induced apoptosis mainly via suppressing the mitochondria-mediated intrinsic apoptosis pathway, but not in an extrinsic manner. Keywords:: silibinin, mitomycin C, mitochondria mediated apoptosis, p53

The pharmacological activity of polyphenolic silibinin from milk thistle (Silybum marianum) is primarily due to its antioxidant property. However, this study found that silibinin promoted sustained superoxide (O(2)(.-)) production that was specifically scavenged by exogenous superoxide dismutase (SOD) in MCF-7 cells, while the activity of endogenous SOD was not changed by silibinin. Previous work proved that silibinin induced MCF-7 cell apoptosis through mitochondrial pathway and this study further proved that O(2)(.-) generation induced by silibinin was also related to mitochondria. It was found that respiratory chain complexes I, II and III were all involved in silibinin-induced O(2)(.-) generation. Moreover, it was found that silibinin-induced O(2)(.-) had protective effect, as exogenous SOD markedly enhanced silibinin-induced apoptosis.

Glial cell line-derived neurotrophic factor (GDNF) exerts its biological effects via a multi-component receptor system including the ligand binding receptor – GDNF family receptor-alpha1 (GFRα1) and the signaling receptor – RET tyrosine kinase. Recently, the neural cell adhesion molecule (NCAM) has been identified as an alternative signaling receptor for GDNF. The purpose of this study was to investigate whether NCAM could mediate the protective effect of GDNF on injured dopamine (DA) neurons and to determine which cytoplasmic signal molecule associated with NCAM was activated while GDNF performing this effect. The results showed that the phosphorylation of NCAM-associated Fyn was upregulated with GDNF treatment, and this upregulation was inhibited by pre-treatment with the NCAM function-blocking antibody. Moreover, pre-treatment with the antibody could abolish the effect of GDNF on promoting the neurite outgrowth of these DA neurons, except for the effect of GDNF on promoting the expression of tyrosine hydroxylase (TH) in these DA neurons. These results suggest that NCAM is involved in the promotive effect of GDNF on the neurite outgrowth in lesioned DA neurons, but not involved in the promotive effect of GDNF on TH expression in these neurons.

Silibinin, which had been used as a hepatoprotectant, was shown to have anticancer activity. In this study we investigated the mechanisms of silibinin-induced apoptosis in human breast cancer MCF-7 cells. Expressions of Fas ligand (FasL), Fas-associated death domain protein (FADD), and Bax were significantly up-regulated in silibinin-treated cells, whilst silibinin induced a conspicuous translocation of Bax to mitochondria and release of cytochrome c to the cytosol. Therefore, both the extrinsic Fas death receptor and intrinsic mitochondrial death pathways played essential roles in silibinin-induced apoptosis. It was also found that silibinin markedly decreased protein expression of SIRT1, a mammalian homologue of yeast Sir2, which was proved to have a role in sequestering Bax away from mitochondria. Insulin-like growth factor 1 receptor (IGF-1R), a receptor tyrosine kinase with a crucial role in malignancy development, is expressed in most human primary breast carcinomas. Our results showed that silibinin-induced apoptosis was significantly reinforced by blocking IGF-1R signaling with tyrphostin AG1024, a specific inhibitor of IGF-1R autophosphorylation. Up-regulation of FADD, downregulation of SIRT1 expression, and activation of the mitochondrial death pathway were apparently enhanced by AG1024 in the silibinin-treated MCF-7 cells. Keywords:: silibinin, insulin-like growth factor 1 receptor (IGF-1R), MCF-7 cell, apoptosis

A highly efficient one-pot, two-step microwave procedure has been developed for the synthesis of 4-substituted 1-heteroarylpiperazines. Microwave heating of heteroaryl chlorides with 1,4-diazabicyclo[2.2.2]octane (DABCO) at 160 °C for 15 min yielded 1-heteroaryl-4-(2-chloroethyl)piperazines, which could be further reacted with various nucleophiles, again under microwave irradiation conditions, to give an array of 4-substituted 1-heteroarylpiperazines in good to excellent yields.

A variety of aryl nitriles were prepared in excellent yield from the palladium(II) acetate–catalyzed cross‐coupling of aryl triflates and zinc cyanide under microwave irradiation conditions. To facilitate purification, polymer‐supported triphenylphosphine was used as the palladium ligand. Comparison to the corresponding thermal conditions revealed much shorter reaction times with comparable yields.

Aim: To explore the intracellular mechanisms underlying the survival/differentiation effect of the glial cell line-derived neurotrophic factor (GDNF) on dopamine (DA) cells. Methods: Midbrain slice culture and primary cell culture were established, and the cultures were divided into 3 groups: control group, GDNF group, and the phosphatidylinositol 3-kinase/Akt (PI3-K/Akt) pathway-inhibited group. Then the expression of tyrosine hydroxylase (TH) was detected by immunostaining as well as Western blotting. Results: GDNF treatment induced an increase in the number of TH-immunoreactive (ir) cells and the neurite number of TH-ir cells, as well as in the level of TH expression in cultures (Number of TH-ir cells in the slice culture: control group, 8.76±0.75; GDNF group, 18.63±0.95. Number of TH-ir cells and neurite number of TH-ir cells in cell culture: control group, 3.65±0.88 and 2.49±0.42; GDNF group, 6.01±0.43 and 4.89±0.46). Meanwhile, the stimulation of cultured cells with GDNF increased the phosphorylation of Akt, which is a downstream effector of PI3-K/Akt. The effects of GDNF were specifically blocked by the inhibitor of the PI3-K/Akt pathway, wortmannin (Number of TH-ir cells in slice culture: PI3-K/Akt pathway-inhibited group, 6.98±0.58. Number of TH-ir cells and neurite number of TH-ir cells in cell culture: PI3-K/Akt pathway-inhibited group, 3.79±0.62 and 2.50±0.25, respectively). Conclusion: The PI3-K/Akt pathway mediates the survival/differentiation effect of GDNF on DA cells.

3-Chloro-1-phenyl-2-pyrazoline and 3-chloro-1-phenyl-1,4,5,6-tetrahydropyridazine were coupled with aryl boronic acids in good yields under microwave heating conditions (140 °C, 5 min).

Facile intramolecular N-arylation catalyzed by CuI/ l -proline has been developed to prepare 6,12b-diaza-dibenzo[a,h]azulen-7-ones and benzo[f]pyrrolo[1,2-a][1,4]diazepin-4-ones in good to excellent yields.

A novel synthesis of 6-methyl-4-phenyl-5-substituted-3,4-dihydropyrimidin-2(1 H )-ones from 6-methyl-4-phenyl-5-halo-3,4-dihydropyrimidin-2(1 H )-ones via the Suzuki–Miyaura reaction is reported. These previously unknown heterocyclic halides are easily prepared using the Biginelli multicomponent reaction followed by halodecarboxylation. The effect of varied substitution at the C-4 position on the cross-coupling reaction is also examined.

Glial-cell-line-derived neurotrophic factor (GDNF) has been shown to protect dopaminergic (DA) neurons against 6-hydroxydopamine (6-OHDA) toxicity. The mechanism underlying the antiapoptosis role of GDNF still needs further studies. We previously observed that nuclear factor-kappaB (NF-κB) signaling pathway, i.e. p65/p52, mediated the antiapoptosis role of GDNF in MN9D cells. Here, the DA cell line MN9D was used to explore the mechanisms underlying NF-κB p65/p52-mediated protection role of GDNF in DA neurons. The results showed that GDNF pretreatment blocked the apoptotic effects induced by 6-OHDA, with the upregulation of the antiapoptotic protein, Bcl-2 and Bcl-w, as well as the downregulation of the proapoptotic proteins, Bax and Bad. Furthermore, when sip100 plasmids were transfected into MN9D cells to inhibit the expression of p100, which was the precursor of p52, the effects of GDNF on upregulating Bcl-2 and Bcl-w were attenuated. These results indicated that GDNF could protect MN9D cells from apoptosis induced by 6-OHDA via upregulating Bcl-2 and Bcl-w expressions and downregulating Bax and Bad expressions. Moreover, NF-κB p65/p52 signaling mediated the effects of GDNF on Bcl-2 and Bcl-w expressions.

Flowering time (i.e., heading date in crops) is an important ecological trait that determines growing seasons and regional adaptability of plants to specific natural environments. Rice ( Oryza sativa L.) is a short-day plant that originated in the tropics. Increasing evidence suggests that the northward expansion of cultivated rice was accompanied by human selection of the heading date under noninductive long-day (LD) conditions. We report here the molecular cloning and characterization of DTH2 (for Days to heading on chromosome 2 ), a minor-effect quantitative trait locus that promotes heading under LD conditions. We show that DTH2 encodes a CONSTANS-like protein that promotes heading by inducing the florigen genes Heading date 3a and RICE FLOWERING LOCUS T 1 , and it acts independently of the known floral integrators Heading date 1 and Early heading date 1 . Moreover, association analysis and transgenic experiments identified two functional nucleotide polymorphisms in DTH2 that correlated with early heading and increased reproductive fitness under natural LD conditions in northern Asia. Our combined population genetics and network analyses suggest that DTH2 likely represents a target of human selection for adaptation to LD conditions during rice domestication and/or improvement, demonstrating an important role of minor-effect quantitative trait loci in crop adaptation and breeding.

Chinese medicines (CMs) are increasingly being used for the treatment of tumors because of their unique advantages. The induction of tumor cell apoptosis is an important method of tumor treatment. Caspase-3 is a member of the caspase (cysteine aspartic proteinases) family of enzymes, which are the major inducers of apoptosis. Caspase-3 activity is often measured in the context of research into anti-tumor drugs that target apoptosis. Many studies have shown that CMs upregulate the expression of caspase-3 in tumor cells via extrinsic and/or intrinsic pathways, removing endogenous suppression of apoptosis and promoting tumor cell death. Therefore, several CMs fulfill the criteria for anti-tumor drugs. In this paper, we review the efficacy of 14 Chinese herbal medicines, across a wide range applications, and discuss their effects on caspase-3 activity in tumor cells.

The heterocycles are prepared in excellent yield via PyBOP-promoted reaction of o-halobenzylamines with carboxylic acids followed by intramolecular N-arylation of the amide products (I), (III) and (V).

Halo derivatives of type (VI) and (XI) are prepared via the corresponding carboxylic acids following a treatment with NaI or NaBr under conditions A).

A series of α,α-disubstituted amines have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic, and heteroaromatic nitriles. Key to this reported procedure is the unprecedented addition of the Grignard reagent to the nitrile under heating by microwave irradiation which both significantly improves reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5–10 min at 100 °C followed by rapid reduction with sodium borohydride to give the target amines.

We present a high-temperature-resistant distributed Bragg reflector fiber laser photowritten in Er/Yb codoped phosphosilicate fiber that is capable of long-term operation at 500 °C. Highly saturated Bragg gratings are directly inscribed into the Er/Yb fiber without hydrogen loading by using 193 nm excimer laser. After subjected to a significant decay at elevated temperature, the stabilized gratings are strong enough for laser oscillation. The laser operates in robust single longitude mode with output power more than 1 dBm and signal-to-noise ratio better than 70 dB over the entire temperature range from room temperature to 500 °C.

A highly efficient procedure was developed for the microwave-assisted synthesis of N-heteroaryl-4-(2-chloroethyl)piperazines and N-heteroaryl-4-(2-chloroethyl)piperidines. Microwave irradiation of electron deficient heteroaryl chlorides with 1,4-diazabicyclo[2.2.2]octane (DABCO) at 160 °C for 15 min led to N-heteroaryl-4-(2-chloroethyl)piperazines in good to excellent yields. In a similar manner, microwave irradiation of electron deficient heteroaryl chlorides with quinuclidine at 180 °C for 15 min provided N-heteroaryl-4-(2-chloroethyl)piperidines in good to excellent yields. Extension of the method was demonstrated by the development of a one-pot, two-step microwave-assisted protocol for the synthesis of 4-(2-acetoxyethyl)-substituted N-heteroarylpiperazines and N-heteroarylpiperidines to demonstrate the production of a small library in a parallel fashion.

A variety of aryl nitriles were prepared in excellent yield from the palladium(II) acetate–catalyzed cross‐coupling of aryl triflates and zinc cyanide under microwave irradiation conditions. To facilitate purification, polymer‐supported triphenylphosphine was used as the palladium ligand. Comparison to the corresponding thermal conditions revealed much shorter reaction times with comparable yields.

Dual-polarization distributed Bragg reflector fiber laser (26 mm length) in Er-doped fiber with beat-frequency of ∼20 MHz (significantly lower than ∼1 GHz reported earlier) that is capable of detecting 16 MHz ultrasound has been demonstrated.