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A more detailed description about the selected exposures and counterpart GWASs. And how we conducted the pleiotropy analysis with these datasets. (DOCX 95 kb)

Statistical description of Inverse-variance weighted method. (DOCX 71 kb)

Genome-wide Association studies (GWAS) and candidate gene studies have identified the association between BIN1 rs744373 variant and Alzheimer’s disease (AD) in Caucasian populations. Recently, a number of studies investigated the association between BIN1 rs744373 and AD in Asian populations. However, both positive and negative results have been identified. We consider that the relatively small sample sizes may lead to the lower statistical power. Here, we selected 71,168 samples (22,395 AD cases and 48,773 controls) from 19 articles containing 38 studies and reinvestigated this association using meta-analysis method. We observed a significant genetic heterogeneity and identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 × 10−07, OR = 1.12, and 95% confidence interval (CI) 1.07–1.17). In subgroup analysis, we not only identified significant genetic heterogeneity in East Asian but also in Caucasian. The subgroup meta-analysis only revealed significant association between rs744373 polymorphism with AD in the Caucasian populations (P = 3.38 × 10−08, OR = 1.16, 95% CI 1.10–1.22), but not in the East Asian populations (P = 0.393, OR = 1.057, and 95% CI 0.95–1.15). The regression analysis suggested no significant publication bias. In summary, this large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD in Caucasian populations but not in the East Asian populations.

Halloysite nanotubes (HNTs) were modified with Fe3O4 to form novel magnetic HNTs-Fe3O4 composites, and the composites were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometer (VSM). The as-obtained results indicated that Fe3O4 nanoparticles were successfully installed on the surface of HNTs. The adsorption of UO22+ on HNTs-Fe3O4 was investigated as a function of solid content, contact time, pH, ionic strength and temperature by batch experiments. The consequences revealed that the adsorption of UO22+ onto HNTs-Fe3O4 was strongly dependent on pH and ionic strength. Equilibrium data fitted well with the Langmuir isotherm. The experimental results demonstrated that the adsorbents with HNTs-Fe3O4 had the largest adsorption capacity of 88.32 mg/g for UO22+.

The Stille coupling of (E)-α-stannyl-α,β-unsaturated esters with alkynyl bromides in DMF in the presence of Pd(PPh3)4 and CuI gave (Z)-2-ethoxycarbonyl-1,3-enynes in good yields. The latter underwent the palladium-catalysed hydrostannylation with tributyltin hydride in THF at room temperature to afford (1E,3E)-2-ethoxycarbonyl-3- stannyl-1,3-dienes in good yields with high regio- and stereoselectivities.

Aggregation of $\beta $ -amyloid ( $\text{A}\beta )$ is one of the early events in Alzheimer’s disease (AD) pathology and is considered to initiate the amyloid cascade. It is presumed that $\text{A}\beta $ plaque might coexist with biogenic magnetite. In order to understand the combined effect and mechanism of the biogenic magnetite and $\text{A}\beta $ in AD, it is necessary to clarify the role of the magnetite in $\text{A}\beta $ aggregation. Due to the magnetic characteristic of the magnetite, it possibly mediates the effect of environmental magnetic field (MF) on $\text{A}\beta $ aggregation. Here, we preliminarily characterized the morphology of $\text{A}\beta _{40}$ aggregation coincubated with a magnetic nanoparticle coated with SiO2 (MNP-SiO2) in the presence of an external extremely low-frequency MF (ELF MF) exposure. Coincubation with MNP-SiO2 accelerated $\text{A}\beta _{40}$ aggregation and MF exposure led to more heterogeneous $\text{A}\beta $ species. The results indicated that the exposure of ELF MF and MNP-SiO2 could alter the $\text{A}\beta _{40}$ aggregation. It will provide insights to understand the roles of ELF MF exposure and biogenic magnetite in the AD pathology.

In this study, the rare earth element Y was added to C f /Mg composite to improve the interfacial bonding strength. 60 vol% C f /Mg composites containing different Y content were fabricated by pressure infiltration method. An interfacial layer with nano-scale formed between C f and Mg–Y alloys. The interfacial products were identified to be MgO, Mg 2 Y and Mg 24 Y 5 by energy dispersive X-ray spectroscopy (EDX) and selected area electron diffraction (SAED). Moreover, the interfacial products enhanced the interface bonding strength, which could be confirmed by the increase of interlaminar shear strength (ILSS). In particular, the C f /Mg composite with 5.7 wt% Y addition increases the ILSS by about 120.9% from 46.2 MPa to 102.3 MPa.

In this work, aluminum matrix composites reinforced with diamond particles (diamond/aluminum composites) were fabricated by squeeze casting method. The material exhibited a thermal conductivity as high as 613 W / (m · K). The obtained composites were investigated by scanning electron microscope and transmission electron microscope in terms of the {100} and {111} facets of diamond particles. The diamond particles were observed to be homogeneously distributed in the aluminum matrix. The diamond {111} /Al interface was found to be devoid of reaction products. While at the diamond {100} /Al interface, large-sized aluminum carbides (Al 4 C 3 ) with twin-crystal structure were identified. The interfacial characteristics were believed to be responsible for the excellent thermal conductivity of the material.

Taking the aquaculture area, the number of farming boats and that of aquaculturist as input variables, the aquaculture production as desirable output variable and polluted economic loss as undesirable output variable, this paper conducts SBM model to evaluate the aquaculture efficiency based on the data of 16 aquaculture-developed provinces in China from 2004 to 2011. The results show the efficiency in China has not changed much in recent years with the efficiency values mainly between 0.39 and 0.53, and the efficiency of marine-aquaculture-dominated provinces is generally higher than that of freshwater-aquaculture-dominated ones. To analyze the difference under the efficiency, the panel Tobit model is used with education level factor, training factor, technology extension factor, technical level factor, scale factor and species factor as the efficiency influencing factors. The results show that technology extension factor and technical level factor have significant positive influence.

SiC nanowires have been rarely investigated or explored along their axial direction by transmission electron microscopy (TEM). Here we report the investigation of the cross-section microstructure of SiC nanowires by embedding them into Al matrix. Morphology of SiC nanowires was cylindrical with smooth surface or bamboo shape. Cubic (3C-SiC) and hexagonal structure (2H-SiC) phases were detected by X-ray diffraction (XRD) analysis. High density stacking faults were observed in both the cylindrical and bamboo shaped nanowires which were perpendicular to their axial direction. Selected area electron diffraction (SAED) patterns of the cylindrical and bamboo shaped SiC nanowires both in the perpendicular and parallel direction to the axial direction were equivalent in the structure. After calculation and remodeling, it has been found that the SAED patterns were composed of two sets of diffraction patterns, corresponding to 2H-SiC and 3C-SiC, respectively. Therefore, it could be concluded that the SiC nanowires are composed of a large number of small fragments that are formed by hybrid 3C-SiC and 2H-SiC structures.

A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for the simultaneous quantitative determination of flumetsulam in 20 kinds of complicated plant-derived food grains (rice, wheat, and corn), vegetables (cabbage, celery, tomato, kidney bean, eggplant, potato, radish and leek), fruits (apple, peach, grape and orange), edible mushroom (mushroom), tea (green tea), nuts (almond), oil crops (soybean) and edible oil (peanut oil) was developed and validated using ultra-performance LC coupled with MS/MS. Acetonitrile was the extraction solvent and simultaneous liquid–liquid partitioning was formed by adding anhydrous magnesium sulfate (MgSO4) and sodium chloride (NaCl). The extract was then cleaned up by dispersive-SPE using graphitized carbon black (GCB), almond and peanut oil using Cleanert Florisil, as selective sorbents. The determination of the target compound was achieved in less than 6.0 min using an electrospray ionization source in positive mode (ESI+). Quantification was performed by calibration curves of standards from 0.01–1.0 mg L−1 with r2 = 0.999. Further optimization of sample preparation and determination achieved recoveries between 73.85% and 115.76% for all analytes with RSD values lower than 10% in 20 kinds of plant-derived foods at three levels (10, 50 and 100 μg kg−1).

Matrix alloying is an effective and convenient method to improve the interface bonding strength for continuous carbon fiber reinforced magnesium matrix composites. In this work, rare earth metal Gd was selected as an alloying element to improve the interface bonding of Cf/Mg composite. Cf/Mg composites with different Gd content were fabricated by pressure infiltration method. The effect of Gd addition on the interfacial microstructures and mechanical properties of the composites were investigated. The results showed that the rare earth Gd tended to segregate at interface area to form Gd2O3 layer and particle phase Mg7Gd. Both the interfacial products enhanced the interface bonding strength which can be identified by the increase of interlaminar shear strength (ILSS). In particular, the Gd addition promoted the ILSS and bending strength greatly, with an increase by 60.4% and 25.3% compared with Cf/Mg composite, respectively. The fracture surfaces of the composites were examined by scanning electron microscopy and micrographs were employed to explain the inherent relation between interface characterization and mechanical properties.

Little has been reported on whether abnormal lipid metabolism affects hydrocephalus, although congenital malformations and infectious diseases are major causal factors for hydrocephalus development. In a study on the pathogenesis of atherogenesis in mice, we unexpectedly discovered that hydrocephalus occurred in partial apolipoptotein E (apoE) and low-density lipoprotein receptor (LDLR) double-knockout (apoE/LDLR) mice fed either chow or a high-fat and high-cholesterol diet between the ages of 4 and 12 weeks. In the 12-week-old high-fat and high-cholesterol group, the incidence rate was as high as 15%. Transcription levels of transforming growth factor-β1 (TGF-β1), Smad3, Smad4, and Smad7 in the cortex of the hydrocephalic cerebrum were significant downregulated in 4-week-old mice, but were increased in the 8 and 12-week-old groups compared with that of age-matched nonhydrocephalic mice. The mRNA level of tissue inhibitor of metalloproteinases 1 was significantly increased, whereas matrix metalloproteinase-9 was lower in hydrocephalic mice of all ages. The translation level of TGF-β1 increased in the hydrocephalic brains of 8 and 12-week-old mice. This study provides primary evidence for the connection between lipid metabolic disorder and hydrocephalus development. This may suggest that both hyperglyceridemia and hypercholesterolemia are harmful factors in hydrocephalus development because of adverse effects on TGF-β1/Smad signaling in the brain.

An equilibrium passive sampler based on POM was first used to determine the Cfree of flubendiamide in water/sediment systems. The adsorption of flubendiamide by POM followed a first-order one-compartment uptake model and the POM-water partition coefficient was 1.90. The method was used to compare the efficiency of three biochars which were produced from crofton weed (BC-1, ∼500 °C), macadamia (BC-2, 550–660 °C) and wheat straw (BC-3, 550 °C). The Freundlich fit the sorption isotherm data well and the adsorption capacity was BC-1 > BC-3 > BC-2. The percent removal of the BC-1 was higher in acidic solutions. When different doses of BC-1 were added to two sediments, the Cfree of the flubendiamide was higher in the sediment with a low organic matter content (S-1). With an increase of BC-1, the Cfree was significantly reduced in S-1. A 30-day period of biochar-sediment contact time was sufficient for a reduction of freely dissolved flubendiamide in the case of the two sediments tested. In the combination of biochar addition (5%) and aging time (30 days), the maximum reductions were 87% and 60% in S-1 and S-2. Therefore, the reduction of bioavailability of the flubendiamide and pollution repair can be achieved by this process.

Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting. Transcription activation was measured using a luciferase reporter assay. Transcription factor binding was determined using ChIP-PCR. Xenograft model was established and exposed to radiation with the simultaneous administration of oleuropein. Tumor growth was monitored. We demonstrated that treatment of oleuropein-sensitized ovarian cells with radiation altered the microRNA expression profile. The endogenous expression of miR-299 was suppressed by a hypoxia inducible factor and relieved in response to oleuropein, which in turn suppressed HPSE1 expression and consequently led to increased sensitivity to radiation. Our data elucidates an unappreciated mechanism mediating radiotherapy resistance in ovarian cancer and exploits the potential synergistic effect of oleuropein with radiation, which warrants further clinical investigation.

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an additive flame retardant of high production volume, and frequently detected in biota and environment. However, knowledge on its potential risk and toxicological mechanism still remains limited. In this study, DNA damage, transcriptomic responses and biochemical changes in the liver of zebrafish (Danio rerio) induced by TDCPP were investigated. Zebrafish was exposed to 45.81μg/L (1/100 (96h-LC50)) and 229.05μg/L (1/20 (96h-LC50)) TDCPP for 7 d. The reactive oxygen species (ROS) and GSH contents, in addition to antioxidant enzyme activities in the liver changed significantly, and the mRNA levels of genes related to oxidative stress were alerted in a dose-dependent and/or sex-dependent manner after exposure to TDCPP. Significant DNA damage in zebrafish liver was found, and olive tail moment increased in a concentration-dependent manner. Moreover, exposure of TDCPP at 45.81μg/L level activated the cell cycle arrest, DNA repair system and apoptosis pathway in male zebrafish, and 229.05μg/L TDCPP exposure inhibited those pathways in both male and female zebrafish. The cell apoptosis was confirmed in TUNEL assay as higher incidence of TUNEL-positive cells were observed in zebrafish exposed to 229.05μg/L TDCPP. Our results also indicated that males were more sensitive to TDCPP exposure compared with females. Taken together, our results showed that TDCPP could induce oxidative stress, cell cycle arrest, DNA damage and apoptosis in adult zebrafish liver in sex- and concentration-dependent manners.

Photoelectrochemical process is an environmentally friendly technology and has a wide application in the control of environmental pollutants. Efficient nanophotocatalysts responsive to visible light are still highly attractive. In this work, α-Fe

It is a great challenge to fabricate piezoresistive sensors that possess high elasticity, large-area compliance, and excellent detectability to satisfy both extremely tiny and large human activity monitoring. Herein, a novel and facile strategy is reported to manufacture highly elastic channel crack-based gold@PU sponge piezoresistive material. The elastic 3D conductive network is successfully prepared by gold ion sputtering, and channel cracks are skillfully designed on the 3D sponge skeletons. Such novel structure makes these fabricated sensors are capable of monitoring both tiny and large human motions, which originate from the nanocrack joint sensing mechanism and physical contact of conductive interconnected network. Meanwhile, our sensors possess excellent elasticity, fast response time (9 ms), and ultralow detection limit (0.568 Pa), as well as good reproducibility over 1000 cycles. The desirable elasticity of channel crack-based gold@PU sensor is comparable to recently reported pressure sensors, together with advantages of reliable fabrication and large-area compliance, makes them attractive in various electronic devices, for example, biological health monitoring, sport performance monitoring, and man-machine interfaces.

Background Type VI collagen is supposed to be a regulation factor in adipogenesis. This study aimed to assess the promoting effect of vitamin C (VC) on adipogenic differentiation of preadipocytes as well as its mechanism. Methods Five sets of different combinations of chemicals were used to inhibit synthesis of type I to VI collagens, blocking ERK1/2 phosphorylation during adipogenesis of 3T3-L1 preadipocytes. Furthermore, to explore whether collagen VI plays a critical role during adipogenesis, specific knockdown of collagen VI was performed by using RNA interference. The morphology and expression patterns of several target factors involved in adipogenesis were assessed at various time points. Results A reduction in ERK1/2 phosphorylation and an increase in collagen VI and adipogenic-specific factors, such as C/EBPβ, PPARγ and C/EBPα, were observed after treating adipogenic 3T3-L1 cells with AA2P, a stable derivative of VC. Inhibition of collagen synthesis by ethyl-3, 4-dihydroxybenzoate (EDHB) or by specific knockdown of collagen VI by RNAi could promote ERK1/2 phosphorylation. The ERK1/2 phosphorylation in both cases could be attenuated by AA2P treatment. In addition, the inhibition of ERK1/2 phosphorylation by U0126, a highly selective inhibitor of both MEK1 and MEK2 and a type of MAPK/ERK kinase, up-regulated the expression of collagen VI, while it down-regulated the adipogenic-specific factors. Conclusion AA2P could up-regulate the expression of collagen VI by attenuating ERK1/2 phosphorylation, further up-regulating adipocyte-specific factors, thus finally promoting the adipogenesis of 3T3-L1 preadipocytes. Electronic supplementary material The online version of this article (10.1186/s12986-017-0234-y) contains supplementary material, which is available to authorized users.

Enterovirus 71 (EV71) is a pathogenic factor of severe hand, foot, and mouth disease (HFMD). No vaccine or specific treatment is currently available for EV71 infection. Hence, we developed a buccal mucoadhesive gel containing matrine to protect against HFMD. Mucoadhesive gels were prepared by Carbopol 974P and were combined with Carbopol 971P, sodium carboxymethyl cellulose (CMC-Na), or hydroxypropylmethy cellulose (HPMC K100M). The formulations were characterized in terms of tensile testing and continuous flow techniques for mucoadhesion. The rheological studies and in vitro drug release characteristics were also investigated. The results showed that combinations of two polymers significantly improved mucoadhesion, especially Carbopol 974P blended with HPMC. Carbopol 974P to HPMC blend ratios of 1:1 and 2:1 induced better mucoadhesion in the tensile test and continuous flow method, respectively. The most sustained release was obtained at a Carbopol 974P to HPMC ratio of 2.5:1. A predominantly non-Fickian diffusion release mechanism was obtained. The gel containing 2.5% Carbopol 974P combined with 1% HPMC showed good mucoadhesion properties and sustained drug release.

International audience; This study aims to explore a therapeutic tool that kills pathogens by using mechanical force other than temperature. We fabricated a device that generates a swing magnetic field (sMF) with low-heat production and then evaluated the killing effect of magnetotactic bacteria MO-1 on Staphylococcus aureus (S. aureus) under the sMF. S. aureus was only killed under the sMF when attached to MO-1 cells. The killing efficiency increased with increasing attachment ratio of MO-1 cells to S. aureus. Treatment with antibody-coated MO-1 cells under the sMF improved the healing of S. aureus-infected wound. The theoretical analysis demonstrated that MO-1 cells generated a mechanical force of approximately 8 kPa under the sMF, thereby exerting on S. aureus and inducing cell death. The proposed platform, which uses magnetotactic bacteria under the sMF to generate mechanical force, provides a basis for development of therapeutic tools to treat infectious diseases. (C) 2016 Elsevier Inc. All rights reserved.

The effect of AA2P on adipogenesis is dose-dependent: a 3T3-L1 preadipocytes were seeded on 12-well plate with growth medium (DMEM, 10% new-born calf serum, penicillin (100 U/ml), streptomycin (100 mg/mL) and 2 mM L-glutamine) to let the cells reached 100% confluent. Two days later, the cells were induced for mature adipocytes with cocktail adipogenic induction medium (growth medium supplemented with 1.7 μM insulin) for an additional 2 days. The medium was finally replaced with growth medium for 10 more days. AA2P was added from the D0 to D14 at final concentrations of 0, 100, 250 and 500 μM, respectively; b On day 14, the cells were stained with Oil red O; The lipid the staining was quantified by extracting the dye with 100% isopropanol and measuring the absorbance at 520 nm. Values are expressed as the mean ± SEM. *P

The interaction of magnetic nanoparticles (MNPs) with various magnetic fields could directly induce cellular effects. Many scattered investigations have got involved in these cellular effects, analyzed their relative mechanisms, and extended their biomedical uses in magnetic hyperthermia and cell regulation. This review reports these cellular effects and their important applications in biomedical area. More importantly, we highlight the underlying mechanisms behind these direct cellular effects in the review from the thermal energy and mechanical force. Recently, some physical analyses showed that the mechanisms of heat and mechanical force in cellular effects are controversial. Although the physical principle plays an important role in these cellular effects, some chemical reactions such as free radical reaction also existed in the interaction of MNPs with magnetic fields, which provides the possible explanation for the current controversy. It is anticipated that the review here could provide readers with a deeper understanding of mechanisms of how MNPs contribute to the direct cellular effects and thus their biomedical applications under various magnetic fields.

Screened the MOI value of the lentivirus and detected the knockdown efficiency of Col VI: a 5 × 104 3T3-L1 preadipocytes/ml were plated in 12-well plates overnight and infected with Lenti-ColVI-GFP lentivirus by addition of lentivirus diluted into 0.5 ml of Dulbecco’s modified eagle medium (DMEM) containing 5% NBCS and polybrene at the MOI of 0, 20, 50 and 100 for 12 h at 37 °C. The medium was then replaced with growth medium until it reached 100% confluence. Adipogenic induction was initiated after 48 h of confluence. The controls were infected with NC lentivirus (I + Lenti-GFP); b After screening out the optimal MOI value of the lentivirus, we detected the knockdown efficiency of Col VI using real-time quantitative reverse transcription. Values are expressed as the mean ± SEM. **P

The DNA damage checkpoint is activated in response to DNA double-strand breaks (DSBs). We had previously shown that chromatin assembly mediated by the histone chaperone Asf1 triggers inactivation of the DNA damage checkpoint in yeast after DSB repair, also called checkpoint recovery. Here we show that chromatin assembly factor 1 (CAF-1) also contributes to chromatin reassembly after DSB repair, explaining its role in checkpoint recovery. Towards understanding how chromatin assembly promotes checkpoint recovery, we find persistent presence of the damage sensors Ddc1 and Ddc2 after DSB repair in asf1 mutants. The genes encoding the E3 ubiquitin ligase complex Rtt101Mms1 are epistatic to ASF1 for survival following induction of a DSB, and Rtt101Mms1 are required for checkpoint recovery after DSB repair but not for chromatin assembly. By contrast, the Mms22 substrate adaptor that is degraded by Rtt101Mms1 is required for DSB repair per se. Deletion of MMS22 blocks loading of Rad51 at the DSB, while deletion of ASF1 or RTT101 leads to persistent Rad51 loading. We propose that checkpoint recovery is promoted by Rtt101Mms1-mediated ubiquitylation of Mms22 in order to halt Mms22-dependent loading of Rad51 onto double-stranded DNA after DSB repair, in concert with the chromatin assembly-mediated displacement of Rad51 and checkpoint sensors from the site of repair.

Two monomers containing naphthalene, 4,4′-di(1-naphthoxy)benzophenone (DNOBN) and 4,4′-bis(1-naphthoxy)diphenyl sulfone (BNODPS), were prepared by the condensation reactions of 4,4′-difluorobenzophenone and 4,4′-dichlorodiphenyl sulfone with 1-naphthol, respectively. Novel poly(aryl ether ketone)s (PAEKs) and poly(aryl ether ketone sulfone)s containing 1,4-naphthylene units were synthesized from DNOBN and BNODPS via the electrophilic Friedel–Crafts acylation polycondensation with various aromatic diacid dichlorides, in the presence of anhydrous aluminum chloride and N-methyl-2-pyrrolidone in 1,2-dichloroethane. Because of the incorporation of 1,4-naphthylene units, the resulting PAEKs and poly(aryl ether ketone sulfone)s exhibited outstanding thermal stability and improved solubility in common organic solvents. The glass transition temperatures are above 200°C, and the temperatures at a 5% weight loss are above 548°C under nitrogen atmosphere. All these polymers are amorphous and can form strong, transparent, and flexible films with tensile strengths of 89.4–100.6 MPa, Young’s moduli of 2.13–2.65 GPa, and elongations at break of 15.5–25.3%. All these polymers had low dielectric constants of 2.70–2.89 at 1 MHz and low water sorption of 0.51–0.59%.

Magnesium (Mg) alloy containing 1 wt% Yttrium (Y) reinforced with 60 vol% carbon fiber (C f ) composites was fabricated by the pressure infiltration method. The morphological study with Y addition in the composite revealed that the Y element was prone to segregate on the surface of the carbon fiber during the fabrication process, forming plate-like intermetallic compound Mg 2 Y. The mechanical properties of the composite were investigated by a flexure test and a short-beam shear test. The results showed that the addition of Y element to the composite improved the bending strength and interlaminar shear strength greatly. A study of the fracture mechanism uncovered the important role of Y addition on the interface bonding strength of the C f /Mg composite.

Introduction Qi-Lian-Gui-Shou Tang (QLGST) is a Chinese herb formula composed of Astragalus mongholicus , Coptis chinensiss , Radix Angelicae Sinensis , and Radix Polygoni Multiflori , and is normally used for treatment of patients with acute cerebral ischemic injury in Xuanwu Hospital, Capital Medical University, China. This study explores the efficacy and underlying mechanism of QLGST in a rat model with acute ischemic stroke. Methods Male Sprague-Dawley rats ( n = 95) were subjected to sham operation or middle cerebral artery occlusion (MCAO) for 2 h to induce ischemia followed by 72 h reperfusion with or without administration of QLGST. QLGST at low (19.58 g/kg), moderate (39.16 g/kg) and high dosage (78.32 g/kg) ( N = 19 each group) was administrated by gavage starting 30 min after reperfusion, twice a day for 3 days. Behavioral deficit was tested after 72 h reperfusion, followed by infarct volume and cell apoptosis, detected by TTC and TUNEL staining, respectively. The expression of activated proteins in Akt/GSK3β pathway was assessed by western blot and immunofluorescence staining. Results QLGST at all three dosages decreased neurological functional impairment, but the infarct volume was only significantly decreased by QLGST at the moderate dosage (clinic equivalent dose) compared to MCAO model without treatment. Furthermore, QLGST at moderate dosage inhibited neuronal apoptosis and increased the activation of Akt/GSK3β pathway as compared to MCAO model without treatment. Conclusion Our results exhibited the neuroprotective effect of Chinese herb formula QLGST on acute ischemic brain injury in a rat model. We suggest this effect might be mediated by activation of the protective signaling Akt/GSK3β pathway.

Tryptase is a serine protease with a variety of biological functions. Recently, elevated serum tryptase has been detected in certain patients with acute myeloid leukemia (AML). However, the underlying mechanism for the regulation of tryptase expression remains elusive. In this study, we aimed to investigate the role of stem cell factor (SCF)/C-KIT signaling in regulating the expression of tryptase in AML cells. We found a significant positive correlation between tryptase and C-KIT expression levels in AML patients. Furthermore, real-time PCR, Western blot and ELISA analysis showed that SCF upregulated tryptase mRNA and protein expression in U937 cells, and that this effect was abolished by pretreatment with PD98059 and SB230580. In addition, levels of phosphorylated ERK1/2 and p38MAPK correlated with tryptase levels. Taken together, these data suggest that the expression of tryptase is regulated by SCF/C-KIT signaling via the ERK1/2 and p38MAPK pathways.

The heterogeneous formylation of aryl halides with HCO2Na at atmospheric pressure by carbon monoxide was readily achieved in the presence of the diphosphino-functionalised MCM-41-supported palladium complex in DMF to afford the corresponding aromatic aldehydes in good to excellent yields. This heterogeneous palladium catalyst can be recovered by simple filtration and reused 10 times without any loss of activity.

In the present work, a β titanium alloy reinforced by trace TiB whiskers and TiC particles was fabricated by common casting and hot-forging. For comparative study, the unreinforced titanium matrix alloy was also fabricated by the same casting and forging process. The microstructure, room temperature, tensile properties and fracture characteristics of the composite and the matrix alloy are presented and discussed. Microstructural analysis of the composite revealed that the reinforcements were uniformly dispersed after forging. The size of the β grains in the composite was refined after solution treatment under the β field. The secondary α lath was also refined during aging heat treatment by the addition of trace boron and carbon. The results of the tensile tests show that the improvement in the strength of the composite can be attributed to the refinement in the grain size and the secondary α lath, while the remarkable reduction in the ductility can be ascribed to the cracking of the reinforcements and the decohesion at the interface between the reinforcements and the matrix.

Pseudomonas citronellolis SJTE-3, isolated from the active sludge of a wastewater treatment plant in China, can utilize a series of environmental estrogens and estrogen-like toxicants. Here, we report its whole-genome sequence, containing one circular chromosome and one circular plasmid. Genes involved in estrogen biodegradation in this bacterium were predicted.

Gibberellin (GAs) plays the important role in the regulation of grape developmental and growth processes. The bioinformatics analysis confirmed the differential expression of GA2, GA3, and GA20 gibberellin oxidase genes (VvGA2oxs, VvGA3oxs, and VvGA20oxs) in the grape genome, and laid a theoretical basis for exploring its role in grape. Based on the Arabidopsis GA2oxs, GA3oxs, and GA20oxs genes already reported, the VvGA2oxs, VvGA3oxs, and VvGA20oxs genes in the grape genome were identified using the BLAST software in the grape genome database. Bioinformatics analysis was performed using software such as DNAMAN v.5.0, Clustalx, MapGene2Chrom, MEME, GSDS v.2.0, ExPASy, DNAsp v.5.0, and MEGA v.7.0. Chip expression profiles were generated using grape Affymetrix GeneChip 16K and Grape eFP Browser gene chip data in PLEXdb. The expression of VvGA2oxs, VvGA3oxs, and VvGA20oxs gene families in stress was examined by qRT-PCR (Quantitative real-time-PCR). There are 24 GAoxs genes identified with the grape genome that can be classified into seven subgroups based on a phylogenetic tree, gene structures, and conserved Motifs in our research. The gene family has higher codon preference, while selectivity is negative selection of codon bias and selective stress was analyzed. The expression profiles indicated that the most of VvGAox genes were highly expressed under different time lengths of ABA (Abscisic Acid) treatment, NaCl, PEG and 5 &deg, C. Tissue expression analysis showed that the expression levels of VvGA2oxs and VvGA20oxs in different tissues at different developmental stages of grapes were relatively higher than that of VvGA3oxs. Last but not least, qRT-PCR (Real-time fluorescent quantitative PCR) was used to determine the relative expression of the GAoxs gene family under the treatment of GA3 (gibberellin 3) and uniconazole, which can find that some VvGA2oxs was upregulated under GA3 treatment. Simultaneously, some VvGA3oxs and VvGA20oxs were upregulated under uniconazole treatment. In a nutshell, the GA2ox gene mainly functions to inactivate biologically active GAs, while GA20ox mainly degrades C20 gibberellins, and GA3ox is mainly composed of biologically active GAs. The comprehensive analysis of the three classes of VvGAoxs would provide a basis for understanding the evolution and function of the VvGAox gene family in a grape plant.

Background The elderly population is at risk of osteoarthritis (OA), a common, multifactorial, degenerative joint disease. Environmental, genetic, and epigenetic (such as DNA hydroxymethylation) factors may be involved in the etiology, development, and pathogenesis of OA. Here, comprehensive bioinformatic analyses were used to identify aberrantly hydroxymethylated differentially expressed genes and pathways in osteoarthritis to determine the underlying molecular mechanisms of osteoarthritis and susceptibility-related genes for osteoarthritis inheritance. Methods Gene expression microarray data, mRNA expression profile data, and a whole genome 5hmC dataset were obtained from the Gene Expression Omnibus repository. Differentially expressed genes with abnormal hydroxymethylation were identified by MATCH function. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the genes differentially expressed in OA were performed using Metascape and the KOBAS online tool, respectively. The protein–protein interaction network was built using STRING and visualized in Cytoscape, and the modular analysis of the network was performed using the Molecular Complex Detection app. Results In total, 104 hyperhydroxymethylated highly expressed genes and 14 hypohydroxymethylated genes with low expression were identified. Gene ontology analyses indicated that the biological functions of hyperhydroxymethylated highly expressed genes included skeletal system development, ossification, and bone development; KEGG pathway analysis showed enrichment in protein digestion and absorption, extracellular matrix–receptor interaction, and focal adhesion. The top 10 hub genes in the protein–protein interaction network were COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A1, COL8A1, COL11A1, and COL24A1. All the aforementioned results are consistent with changes observed in OA. Conclusion After comprehensive bioinformatics analysis, we found aberrantly hydroxymethylated differentially expressed genes and pathways in OA. The top 10 hub genes may be useful hydroxymethylation analysis biomarkers to provide more accurate OA diagnoses and target genes for treatment of OA.

Software quality has become a key factor affecting the overall quality of the smart meter. To improve the reliability of the smart meter software, this paper studies the software failure modes and influence analysis of the smart meter based on SFMEA, analyzes software failure modes and mechanisms, and establishes fault-knowledge base; the key technologies of static testing, dynamic testing, black-box testing and white-box testing were carried out for different software failure modes. The test programs of the life cycle of the smart meter software and the support of the automated testing tools are designed to improve the breadth and depth of the software testing, improve the reliability, reduce the operational failure and improve the service level of the electricity.

Methylenetetrahydrofolate reductase (MTHFR) has been demonstrated to be involved in carcinogenesis. Increasing individual studies have investigated the role of MTHFR C677T polymorphism in gastric cancer pathogenesis, but with inconsistent findings. The aim of this study was to clarify the potential association of the MTHFR C677T polymorphism with gastric cancer risk by pooling all available data from published case–control studies. We searched the PubMed, Embase, Web of Science, and Wanfang databases for all relevant publications to date. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated. Stratified analysis and sensitivity analysis were also carried out to estimate the strength of this association. A total of 25 case–control studies with 6,572 cases and 9,584 controls were retrieved. Overall, the ORs under five contrast models indicated that the MTHFR C677T variant was positively associated with gastric cancer risk (ORT vs. C = 1.21, 95 % CI 1.10–1.34, P OR

Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis.We searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association.Eleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR DD versus II=1.81, 95% CI 1.23-2.66, P=0.003; OR ID versus II=1.50, 95% CI 1.25-1.80, P0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed.Meta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.

A clean procedure for the synthesis of tetrahydrobenzo[c]xanthenes was established in the presence of a functional ionic liquid, 1-butyl-(4-dimethylamino)pyridinium hydroxide [BDMAP][OH]. The reaction was carried out via the one-pot multi-component condensation of aromatic aldehydes, cyclic 1,3-dicarbonyl compounds, and α-naphthol in aqueous media, to afford good to excellent yields ranging from 80 to 85 % within 60–90 min. After the reaction, the catalyst could be recycled and reused several times without a noticeable reduction in catalytic activity.

The Heck arylation reaction of aryl iodides with allylic alcohols catalysed by an mesoporous silica (MCM-41)-supported bidentate nitrogen palladium complex [MCM-41-2N-Pd(OAc)2] proceeded smoothly in the presence of tetrabutylammonium chloride (TBAC) in DMF to afford β-aryl ketones in good to excellent yields. This heterogeneous palladium catalyst can be recovered by simple filtration and reused several times without any decrease in activity.

To discuss the relationship between tongue manifestation and the degree of neurological impairment in the patients with acute cerebral infarction.Two hundred patients with first unilateral cerebral infarction were recruited. The relationship between different tongue manifestation and National Institute of Health Stroke Scale (NIHSS) were analyzed.NIHSS scores in the patients from different tongue color groups were analyzed and further analysis demonstrated that the NIHSS score was higher in the patients with red or bluish-purple tongue than that of those with the pink (P0.01). On tongue fur, the NIHSS score in the patients with thick fur was higher than that of those with the thin (P=0.003). NIHSS score in patients with slippery, moist or dry fur was significant different (P=0.003), Further analysis demonstrated that the NIHSS score was higher in the patients with dry fur than that of those with moist fur, and had statistical significance (P=0.01). The NIHSS score was higher in patients from greasy fur group than that of the non-greasy (P=0.002). There was significant difference of NHISS score in the patients with different fur color (P=0.000), and further analysis demonstrated that the NHISS score in white-yellow, yellow fur group were higher than that of the white (P=0.06 or 0.000).The changes of tongue manifestation might be associated with the degree of neurological impairment in the patients with acute cerebral infarction.

Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation.

In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female’s highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species.

Much of our understanding of the function of histone post-translational modifications in metazoans is inferred from their genomic localization and / or extrapolated from yeast studies. For example, acetylation of histone H3 lysine 56 (H3 K56Ac) is assumed to be important for transcriptional regulation in metazoan cells based on its occurrence at promoters and its function in yeast. Here we directly assess the function of H3 K56Ac during chromatin disassembly from gene regulatory regions during transcriptional induction in human cells by using mutations that either mimic or prevent H3 K56Ac. Although there is rapid histone H3 disassembly during induction of some estrogen receptor responsive genes, depletion of the histone chaperone ASF1A/B, which is required for H3 K56 acetylation, has no effect on chromatin disassembly at these regions. During the course of this work, we found that all the commercially available antibodies to H3 K56Ac are non-specific in human cells and in Drosophila. We used H3-YFP fusions to show that the H3 K56Q mutation can promote chromatin disassembly from regulatory regions of some estrogen responsive genes in the context of transcriptional induction. However, neither the H3 K56R nor K56Q mutation significantly altered chromatin disassembly dynamics by FRAP analysis. These results indicate that unlike the situation in yeast, human cells do not use H3 K56Ac to promote chromatin disassembly from regulatory regions or from the genome in general. Furthermore, our work highlights the need for rigorous characterization of the specificity of antibodies to histone post-translational modifications in vivo.