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Aim: The aim of this study was to investigate the effect and molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway. Methods: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods. Results: Compared to the sham group, the spatial memory ability of rats with composited Aβ was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aβ rats. Conclusions: SSF improved memory impairment and neurogenesis disorder induced by composited Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.

Aim: The present study aims to investigate the effect of flavonoids from stem and leaf of Scutellaria Baicalensis Georgi (SSF) on multi-sites phosphorylation of tau protein in the cerebral cortex and hippocampus of rats induced by okadaic acid (OA) and the regulative mechanism of the protein kinases. Methods: The model of AD-like memory impairment and neuronal injuries was established in male SD rats who were microinjected with OA (200 ng/kg) to establish a memory impairment model and screened for successful model rats by Morris water maze on day 21 after surgery. The successful model rats were continuously administered with intragastric infusion (ig) SSF 25, 50 and 100 mg/kg or Ginkgo biloba leaves flavonoids (GLF) 200 mg/kg for 36 d. The relative protein expressed levels of phosphorylated tau protein at sites of Ser199, Ser202, Ser214, Ser404 and Thr231, protein kinases (CDK5, PKA, pTyr216-GSK3β and pSer9-GSK3β) were detected by Western blotting. Results: The relative protein expressed levels of p-tau(Ser199), p-tau(Ser202), p-tau(Ser214), p-- tau(Ser404), p-tau(Thr231) and pTyr216-GSK3β were significantly increased in both cerebral cortex and hippocampus regions of the model rats subjected to intracerebroventricular injection of OA (P Conclusion: The results demonstrated that SSF could inhibit the hyperphosphorylation of tau in rats’ cerebral cortex and hippocampus induced by microinjection of OA, which may be related to the activities of protein kinase CDK5, PKA and GSK3β.

Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by a clonal proliferation derived from primitive hematopoietic stem/progenitor cells. Circular RNAs (circRNAs) have been identified as crucial regulators in the progression of various cancers, including AML. However, the molecular mechanism of AML is still not definite. This study aimed to explore the influences of circ_0012152 on cell development in AML cells and the underlying regulatory mechanism. The expression of circ_0012152, microRNA-625-5p (miR-625-5p) and sex-determining region Y-related high mobility group box 12 (SOX12) was detected by quantitative real-time polymerase chain reaction. The proliferation of AML cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell viability, 5-ethynyl-2'-deoxyuridine incorporation assay for DNA biosynthesis and flow cytometry for cell cycle distribution, respectively. The death of AML cells was detected by flow cytometry. The protein expression was assessed by Western blot assay. Dual-luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationships among circ_0012152, miR-625-5p and SOX12. The expression of circ_0012152 was increased in AML tissues and cells and circ_0012152 knockdown suppressed proliferation and promoted death in AML cells. Further exploration revealed that circ_0012152 inhibited miR-625-5p expression and downregulation of miR-625-5p overturned the effects of circ_0012152 knockdown on proliferation and death in AML cells. Moreover, miR-625-5p targeted SOX12 and circ_0012152 facilitated the expression of SOX12 by relieving miR-625-5p-mediated inhibitory effect on SOX12 in AML cells. Circ_0012152 knockdown suppressed cell proliferation and promoted death by targeting SOX12 mediated by miR-625-5p in AML cells.

Three-dimensional (3D) heteroatom-doped nanostructured carbon materials have gained extensive attention because of their tremendous potential for enhancing supercapacitor performance. Herein, based on a mild carbonization/activation process we successfully developed green/sustainable 3D hierarchically porous nitrogen-doped nanostructure carbon (N–HNC) materials from houttuynia biomass, showing high specific capacitance and high cyclic stability. The as-prepared houttuynia-derived porous carbon material shows a unique flower-like architecture with well-distributed micro/meso pores and a high specific surface area of 2090 m2/g. The assembled supercapacitor based on N–HNC sample shows superior specific capacitance (473.5 F/g at 1 A/g) and remains over 50% of specific capacitance at 20 A/g. The N–HNC based symmetric supercapacitor, constructed with a two-electrode configuration, shows an energy density of 15.99 Wh/kg at 500 W/kg and outstanding capacitance retention of 95.74% even after 10,000 charge-discharge cycles at 10 A/g in an aqueous 6 M KOH electrolyte system. The results highlight the potential of the 3D porous N-doped hierarchical nano-structural carbon materials from houttuynia biomass as candidate electrodes for supercapacitor applications. This study provides an example of using the inherent framework structure of biomass as a precursor to synthesize hierarchically porous nitrogen-doped nanostructure for high-performance supercapacitor applications.

A numerical study on effects of hydrogen direct injection on hydrogen mixture distribution, combustion and emissions was presented for a gasoline/hydrogen SI engine. Under lean burn conditions, five different direct hydrogen injection timings were applied at low speeds and low loads on SI engines with direct hydrogen injection (HDI) and gasoline port injection. The results were showed as following: firstly, with the increase of hydrogen direct injection timing, the hydrogen concentration near the sparking plug first increases and then decreases, reaching the highest when hydrogen direct injection timing is 120°CA BTDC: Secondly, hydrogen can speed up the combustion rate. The main factor affecting the combustion rate and efficiency is the hydrogen concentration near the sparking plug: Thirdly, in comparing with gasoline, the NOX emissions with hydrogen addition increase by an average of 115%. For different hydrogen direct injection timings, the NOX emissions of 120°CA BTDC is the highest, which is 29.9% higher than the 75°CA BTDC. The hydrogen addition make the NOX emissions increase in two ways. On the one hand, the average temperature with hydrogen addition is higher. On the other hand, the temperature with hydrogen addition is not homogeneous, which makes the peak of temperature much higher. In a word, the main factor of NOX emissions is the size of high temperature zone in the cylinder: Finally, because the combustion is more complete, in comparing with gasoline, hydrogen addition can reduce the CO and HC emissions by 32.2% and 80.4% respectively. Since a more homogeneous hydrogen mixture distribution can influence a lager zone in the cylinder and reduce the wall quenching distance, these emissions decrease with the increase of hydrogen direct injection timing. The CO and HC emissions of 135°CA BTDC decrease by 41.5% and 71.4%, respectively, compared to 75°CA BTDC.

Cellulose nanocrystals (CNCs) is an exciting class of sustainable and carbohydrate material, which has great potential applications in molecular adsorption. However, the complex preparation process and limited adsorption capacity of CNCs hinder its commercial application. In this study, we design a novel functional cellulose nanocrystals-based adsorbent by an ingenious mixing of lignin-containing cellulose nanocrystals (LCNCs), sodium alginate (SA), and calcium chloride solution. Benefiting from the sulfonate groups of lignin, carboxyl groups of SA, the maximum adsorptive capability of LCNCs/SA beads for methylene blue was found to be 1181 mg g−1, which was significantly higher than previously reported biomass-based adsorbents. More importantly, LCNCs/SA beads can be reused several times. This strategy can not only improve the adsorption performance of CNCs-based materials, but also simplify the production technology of CNCs, which greatly promote the commercial application of CNCs materials.

A comparative study on effects of homogeneous or stratified hydrogen on combustion and emissions was presented for a gasoline/hydrogen SI engine. Three kinds of injection modes (gasoline, gasoline plus homogeneous hydrogen and gasoline plus stratified hydrogen) and five excess air ratios were applied at low speed and low load on a dual fuel SI engine with hydrogen direct injection (HDI) and gasoline port injection. The results showed that, with the increase of excess air ratio, the brake thermal efficiency increases firstly then decreases and reaches the highest when the excess air ratio is 1.1. In comparison with pure gasoline, hydrogen addition can make the ignition stable and speed up combustion rate to improve the brake thermal efficiency especially under lean burn condition. Furthermore, it can reduce the CO and HC emissions because of more complete combustion, but produce more NOX emissions due to the higher combustion temperature. Since, in the gasoline plus stratified hydrogen mode, the hydrogen concentration near the sparking plug is denser than that of homogeneous hydrogen, the ignition is more stable and faster, which further speed up the combustion rate and improve the brake thermal efficiency. In the gasoline plus stratified hydrogen mode, the brake thermal efficiency increases by 0.55%, the flame development duration decreases by 1.0°CA, rapid combustion duration decreases by 1.3°CA and the coefficient of variation (COV) decreases by 9.8% on average than that of homogeneous hydrogen. However, in the gasoline plus stratified hydrogen mode, due to the denser hydrogen concentration near the sparking plug and leaner hydrogen concentration near the wall, the combustion temperature and the wall quenching distance increase, which make the NOX and HC emissions increase by 14.3% and 12.8% on average than that of homogeneous hydrogen.

Flexible supercapacitors with considerable energy storage performance from green/sustainable materials have attracted significant attention in many fields, such as portable and wearable electronics...

Hydrous ethanol has lower cost and energy consumption during the production process than anhydrous ethanol. Many researchers used hydrous ethanol instead of anhydrous ethanol to manufacture hydrous ethanol-gasoline. The water ratio in hydrous ethanol (ω) determines the energy consumption in the production process of ethanol. However, no one researched the effects of different ω on combustion and emissions of hydrous ethanol-gasoline. So, we prepared five kinds of ethanol with different ω (0, 5%, 10%, 15%, 20% vol.) to research the effects of ω on combustion and emissions. This study adopted combined injection with hydrous ethanol direct injection plus gasoline port injection (HEDI + GPI). The engine speed was 1500 rpm, and λ was 1, the intake manifold absolute pressure was 48 kPa, the direct injection ratio was 20%, five spark timings varied from 5 °CA BTDC to 25 °CA BTDC. The results showed hydrous ethanol prolonged flame development and propagation duration, decreased Tmax and Pmax, delayed APmax. Water increased COVimep, but using hydrous ethanol at the reasonable spark timing would not significantly affect the stability. Meanwhile, when the spark timing was MBT, compared with GE (gasoline/anhydrous ethanol dual fuel) fuel, as ω in GEW (gasoline/hydrous ethanol dual fuel) fuels increased, torque and brake thermal efficiency improved by 1.69%, 1.13%, −0.01%, −0.77%; HC increased by 2.13%, 9.02%, 23.89%, 37.15%; CO decreased by 41.95%, 28.56%, 5.59%, 2.46%; NOx decreased by 10.10%, −0.75%, −0.17%, 4.18%; total PN emissions decreased by 24.07%, 69.57%, 36.34%, 32.45%. Meanwhile, more water caused the size of particles to drop, made particles smaller.

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling. APAP overdose caused severe liver injury in WT mice as indicated by serum parameters, histopathological changes and hepatocyte apoptosis, which were remarkably ameliorated in fat-1 mice. These protective effects of n-3 PUFA were associated with regulation of the prolonged JNK activation via inhibition of apoptosis signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 4 (MKK4) pathway. Additionally, the augment of endogenous n-3 PUFA reduced nuclear factor kappa B (NF-κB) – mediated inflammation response induced by APAP treatment in the liver. These findings indicate that n-3 PUFA has potent protective effects against APAP-induced acute liver injury, suggesting that n-3 dietary supplement with n-3 PUFA may be a potential therapeutic strategy for the treatment of hepatotoxicity induced by APAP overdose.

Impregnated decorative paper was an important wood-based panel finishing material. However, traditional impregnated decorative paper was impregnated with melamine-formaldehyde resin, which will release formaldehyde and harm the human health. To solve this problem, small molecule polyacrylate-polyethylene glycol (PEG) adhesive was used to achieve the non-formaldehyde addition of the impregnation system. The dialdehyde modified CNF (D-CNF), modified by sodium periodate (NaIO4), and triethylenediamine were introduced to enhance the surface properties of the impregnated decorative paper. The results showed that the incorporation of D-CNF and triethylenediamine imparted excellent physical strength and surface properties to impregnated decorative paper. When the dosage of 0.3 wt% D-CNF and 3 mL/100 g triethylenediamine in the compound emulsion, the hardness, abrasion resistant value and surface bonding strength of impregnated decorative paper adhered fiberboard reached 3H, 330 r of damage and 1.13 MPa, respectively. Thus, it could be effectively used for making high-performance formaldehyde-free impregnated decorative paper.

In this paper, on the basis of combined injection technique, three injection modes with five n-butanol/gasoline volume ratios ( ν N ) were put forward, aiming to compare and evaluate the relationship between the injection mode and the combustion and emission characteristics of an n-butanol/gasoline SI engine equipped with an extra hydrogen direct injection system. The results indicated that under low load condition, compared with NGP (n-butanol/gasoline port injection) mode, the NGPD (n-butanol/gasoline combined injection) mode and NGPH (n-butanol/gasoline with hydrogen combined injection) mode can both improve the combustion performance. The peak cylinder pressure of NGPD and NGPH mode was 5.58% and 11.63% higher than that of NGP mode on average, respectively. Furthermore, the combined injection modes concentrated the process of heat release, shortened the combustion duration, increased the power performance and improved the combustion stability at all ν N . As for emissions, the NGPD and NGPH combined modes significantly decreased the HC and CO emissions, but increased the NOX emissions. Among all the test conditions, the NGPH mode with 25% ν N obtained the best combustion quality. Additionally, the effect rules of ν N on combustion and emission characteristics under NGP mode were found to be consistent with those under NGPD and NGPH combined modes.

We report on the fabrication of Nd:YCa4O(BO3)3 (Nd:YCOB) ridge waveguides by combining carbon ion irradiation and precise diamond blade dicing. The guiding and spectroscopic properties of the planar as well as ridge waveguides are investigated. The second harmonic generation (SHG) at 532 nm has been realized through the waveguide structures. With nearly the same input power, the maximum average output powers are 0.56 mW and 0.62 mW, and the maximum conversion efficiencies reach 0.3%W−1 and 0.5%W−1, for planar and ridge waveguides, respectively.

A novel two-stage reheating process with new alloy design has been developed to improve the microstructure morphology of semisolid Al-Si casting aluminum alloy for thixoforming. The process consists of first reheating the material to the liquidus temperature, holding for 5 min, and then lowering to the predetermined two-stage reheating temperature between 843–863 K and holding for 10 min. The experimentally-obtained grain diameter, roundness, and the amount of liquid trapped within the solid phase were characterized, along with the microstructure obtained using the traditional feedstock reheating process. The Wilcox test (with α = 0.05) was then applied to statistically analyze the measured differences in the microstructures obtained using the two different processing routes. It was found that a refined near-spherical structure with uniform globule size, higher sphericity, lower coarsening rate constant, and less entrapped liquid was obtained via the new two-stage reheating process in comparison with the microstructure obtained using the traditional feedstock reheating process.

Split hydrogen direct injection is proved to be a better way to use the hydrogen in the engine. Therefore, a numerical study on effects of split injection proportion on hydrogen mixture distribution, combustion and emissions was presented of a gasoline/hydrogen SI engine with split hydrogen direct injection to investigate the principle of split hydrogen direct injection. Under lean burn condition, six different split injection proportions achieve six kinds of hydrogen mixture distribution, which affect the engine performance a lot. With split hydrogen direct injection, the mixture nearby the spark plug is denser and in other zone is more homogeneous at the same time, which achieve better performances of both efficiency and emissions. As the first injection proportion increases, the cylinder pressure climbs to the highest with first injection proportion of 33% and the NOX, CO and HC emissions decrease continually. When the first injection proportion is 75%, the NOX, CO and HC emissions are respectively 31.6%, 79.3% and 40.6% less than those of single hydrogen direct injection.

Recently, more attention has been paid to the application of biobutanol in spark ignition (SI) engines due to its superior properties among the biofuels. However, the high energy consumption and low efficiency of recovering biobutanol from ABE solution during the fermentation process lead to the high price of biobutanol, which limits its popularization in vehicles. Using ABE directly can solve the problem of high price of bio-butanol. This research explored the performance of an SI engine with ABE port injection (ABEPI) plus gasoline direct injection (GDI) at different excess air ratio (λ = 0.9, 1.0, 1.1, 1.2) and ABE port injection ratio (ABEPIr = 0, 25%, 50%, 75%, 100%). The results show that CA10-90 declines with increasing ABEPIr. CA0-10 and CA0-90 decrease with ABEPIr increasing at λ = 0.9, and first descend and then rise at λ = 1.0, 1.1 and 1.2. The coefficient of variations of IMEP (CoVIMEP) reaches the minimum value at ABEPIr = 75%. As ABEPIr increases, the peak in-cylinder pressure (Pmax), indicated mean effective pressure (IMEP) and brake thermal efficiency (BTE) increase at λ = 0.9 while first increase and then decrease at λ = 1.0, 1.1 and 1.2, reaching the maximum values at ABEPIr = 75%. Hydrocarbon (HC) reaches the minimum value at ABEPIr = 50%. Particle number decreases dramatically as ABEPIr increases from 0% to 50% and remains at an extremely low level when ABEPIr is greater than 50%. In summary, ABE is suitable for SI engine as an alternative fuel and fuels with high ABE ratio (≥50%) can effectively improve the combustion and particle emissions by ABEPI + GDI combined injection.

In this paper, a numerical research on an n-butanol ignition engine with hydrogen direct injection was carried out, aiming to observe the effect of hydrogen blending fractions on idling performance. A three-dimensional dynamic mesh model coupled with a detailed chemical kinetic mechanism of n-butanol oxidation were established to investigate the engine combustion process in CFD software CONVERGE. And the numerical model was validated through experiments. The performance of pressure and temperature inside cylinder, HC and CO emissions and formaldehyde and acetaldehyde emissions with four hydrogen fractions were simulated and analyzed. The simulation results showed that in comparison with pure n-butanol, the peak cylinder pressure increased 18.62%, 22.86% and 25.41% at φ H 2 = 5%, φ H 2 = 10% and φ H 2 = 15%, respectively. Meanwhile, the process of heat release can be accelerated and concentrated by hydrogen blending. The HC and CO emissions decreased gradually with the increase of hydrogen fraction. The largest magnitude of reduced HC and CO emissions was at φ H 2 = 5% as 31.31% and 19.05%, respectively. In terms of unregulated emissions, the acetaldehyde emissions remained a higher level than formaldehyde emissions for all hydrogen fractions at idle condition, and both decreased with the increase of hydrogen fraction. The distribution of formaldehyde and acetaldehyde concentration were closely related to the temperature field inside cylinder. The improvement of acetaldehyde emissions affected by adding hydrogen was more significant than that of formaldehyde emissions. Through hydrogen direct injection, a local hydrogen-enriched area near the spark plug can be formed, which contributed to better combustion performance of n-butanol engine at idle condition.

Cellulose nano-crystals (CNC) have attracted great interests as a novel nanostructured material in recent years, thanks to their excellent mechanical properties, high surface area and lightweight and biocompatibility etc. Due to its low charged group content, CNC prepared from the hydrochloric acid hydrolysis has poor dispersibility in water, which hinders its further applications. In this work, well-dispersed cellulose nano-crystals are successfully prepared using a two-step method, consisting of hydrochloric acid hydrolysis, followed by adsorption of hexadecyl trimethyl ammonium bromide (CTAB) onto CNC. Results show that CTAB at a low concentration (0.13–0.47 mM) provides effective steric barriers to minimize the CNC aggregation, which is supported by TEM images and particle size distribution of CNC. At high CTAB concentrations (>0.5 mM), CNC aggregation occurs, which is due to the “bridging” effect of CTAB.

Extraction of hemicelluloses is a primary step in the conversion of plant biomass to valuable biofuels and chemicals. Hemicellulose is distributed in the fiber cell wall, and the compact structure of the fiber cell wall barricades the transport of hemicelluloses in the extraction process. In this paper we presented a novel microwave-assisted extraction process enhanced with an enzymatic pretreatment to improve the hemicelluloses extraction rate from bagasse. Experimental results showed that the enzyme dosage, alkali concentration and microwave irradiation time were main factors governing the yield of hemicellulose. The optimal conditions of the enzymatic pretreatment were: enzyme dosage of 138 IU/g bagasse and irradiation time of 30 min. Under these conditions, 86% of the hemicellulose in bagasse was extracted. After the enzymatic pretreatment the surface area of bagasse increased significantly which facilitated the subsequent microwave-assisted extraction process.

Background : FLT3-ITD mutation remains a great challenge in treating acute myeloid leukemia (AML) patients, for the high incidence of early relapse and drug-resistant mutations to tyrosine kinase inhibitors (TKIs). The FLT3-ITD mutation results in a significant and sustained activation of downstream signaling pathways. However, the physiological negative regulators of those aberrantly activated pathways have not been fully elucidated. In this study, we aim to identify and exploit a key molecule directly interacting with FLT3 receptor and down-regulating FLT3 associated pathways. Methods: The potential proteins interacting with FLT3 were immunoprecipitated (IP) and screened by mass spectrometry. The binding of phosphatase SHP-1 and FLT3 was verified using co-IP and in situ proximity ligation assay (PLA) in cell lines and primary samples. The phosphatase activity and phosphorylation level of SHP-1 was determined by pNPP phosphatase activity assay and western blot. Biological effects of overexpressed SHP-1 by lentiviral vectors in AML cell-lines were assessed using proliferation, apoptosis and clonal formation assays in vitro and xenografts models in vivo. Plasmids of truncated or mutated structure of SHP-1 were constructed and overexpressed in cells to identify the key domain responsible for binding with FLT3 receptor. An artificial trans-membrane peptide was designed to activate SHP-1 activity and promote apoptosis in AML cells. Results: The researchers performed immunoprecipitations (IP) followed by LC-MS/MS based screen in human leukemia cell line MV4-11 for three times, and found that the phosphatase SHP-1 binds to FLT3. In addition, the interaction between SHP-1 and FLT3-WT or FLT3-ITD was verified by co-IP and in situ proximity ligation assay (PLA) in AML cell lines, primary samples and overexpression model of 293-FT.Partial results are showed in Figure A. Furthermore, in heterozygous cell line molm13 and engineered FLT3-ITD knock-in cell line SKM-1 by crispr/cas9 techonology, combined with PLA, pNPP phosphatase activity assay and western blot, we found that SHP-1 may bind with p-FLT3 and acquired phosphatase activity(Figure B-D). In turn, p-FLT3 itself and some important proteins in the downstream pathway would be dephosphorylated and the signal transmission would be terminated. In FLT3-ITD cells, the phosphorylation level of SHP-1 significantly reduced. By using lentivirus to overexpress or knockdown shp-1 protein in FLT3-WT and FLT3-ITD cells, the biological effects were studied. Experiments on cell apoptosis, proliferation and clonal formation have shown that overexpression of SHP-1 in AML cells may promote apoptosis, inhibit proliferation and clone formation, especially in FLT3-ITD cells. On the contrary, inhibition of shp-1 could promote proliferation and increase the ability of clone formation. Furthermore, DOX-inducible overexpression cell line of SHP-1 was obtained by tet-on virus system and the western blots showed that SHP-1 may inhibit p-ERK and p-STAT5 activity. In vivo experiments of NCG mice showed that, the degree of leukemia infiltration in peripheral blood was decreased in AML transplantation mice induced by DOX to express SHP-1 when compared to control group. Next, according to the analysis of protein structure by computer simulation, we constructed truncated and mutated plasmids and overexpressed in cells, then using PLA to verify the binding , we found that FLT3 interact with N-SH2 domain of SHP-1,exactly the R30 site(Figure E). Therefore, by using specific trans-membrane peptide, the researchers found that it could activate SHP-1 and promote apoptosis in AML cells, especially FLT3-ITD ones, inhibit cell proliferation and the downstream signal pathway of FLT3.Lastly,injection of peptide in subcutaneous tumor model of nude mouse showed that the tumor was significantly smaller than that of the control group(Figure F). Conclusion: We identify a negative regulator, namely phosphatase SHP-1, which directly interacts with FLT3 receptor through the N-SH2 domain and down-regulates FLT3 downstream signaling pathways. Overexpression of SHP-1 promotes apoptosis and inhibits proliferation in cells with FLT3-ITD mutation. Artificial trans-membrane peptides activating SHP-1 can reverse FLT3 associated aberrant signaling, thus providing a new potential strategy to target FLT3-ITD in AML. The possible mechanism is showed in figure G. Disclosures No relevant conflicts of interest to declare.

In this paper, the effect of residual chlorine of hypochlorite (H) on high yield pulping with H2O2/CoSO4of wet stored bagasse was studied. Compared with control sample, the pulp of the bagasse wetstored with H or Ho (without residual chlorine) bleaching waste water had better pulping yield and strength, but the pulp optical property was lost seriously. If it had no requirement on the brightness, the wet storage with H or Ho bleaching waste water was a good method to improve the pulp strength and save clean water. In addition, the wet storage of bagasse using the H bleaching waste water without residual chlorine, the pulping properties was more stable than that of the wet storage using H bleaching waste water with residual chlorine. To the wetstorage with Ho bleaching waste water, the ideal treatment time was 16day.

The constitutive equation of semi-solid 6061 alloy was established according to the thermal simulation compression tests of semi-solid billet of 6061 alloy prepared by near-liquids semi-continuous casting method. Parameters of Bingham model, such as apparent viscosity, had been investigated based on the constitutive equation of semi-solid 6061 alloy. The software ANYCASTING was applied to simulate and analyze the semi-solid die-casting processes of semi-solid 6061 alloy. A well-designed runner and gating system of automobile aluminum alloy part were presented and the casting defect were investigated here utilizing these parameters by simulation. The results show that a well-designed runner and gating system is very important to secure good quality die castings through providing a homogenous mould filling pattern. Most defects of semi-solid casting products can be founded in the final solidification of the parts of casting.

The nonlinear optical property of topological insulator bismuth selenide (Bi2Se3) is found to be well-tailored through ion irradiation by intentionally introducing defects. The increase of the optical modulation depth sensitively depends on the careful selection of the irradiation condition. By implementing the ion irradiated Bi2Se3 film as an optical saturable absorber device for the Q-switched wave-guide laser, an enhanced laser performance has been obtained including narrower pulse duration and higher peak power. Our work provides a new approach of tailoring the nonlinear optical properties of materials through ion irradiation, a well-developed chip-technology, which could find wider applicability to other layered two-dimensional materials beyond topological insulators, such as graphene, MoS2, black phosphours etc.

Parameters of Bingham model had been verified according to the thermal simulation compression tests of semi-solid 6061 aluminum and the equations presented by Stefan. The effects of the mold filling temperature of semi-solid slurry of 6061 aluminum during thixo-diecasting were analyzed. The results showed that such conditions of the mold filling temperature about 625°C, the injection speed changing to 2 m/s from 0.4 m/s when 60% of die cavity had been filled, were ideal to gain solidification in sequence and beneficial to get fully filled semi-solid parts with clear contour. The thixo-diecasting experiments were performed under above optimized conditions.

Effects of deformation temperature and strain rate on deformation behavior of semi-solid 6061 alloy were investigated on Gleeble3800 thermal-mechanical simulator. On basis of the experimental data of semi-solid 6061, a model was established to describe the relationship between the processing parameters and flow stress, which showed that the experimental results and calculation ones fitted well. It would be beneficial to realize the distribution of stress and strain during the semi-solid forming on the basis of numerical simulation technology. This research paper presented the numerical simulation results of the 6061 alloy during the backward extrusion thixoforming process.

To study the effect of flavonoids isolated from aerial parts of Scutellaria baicalensis Georgi (SSF) on cerebral damage induced by okadaic acid (OA) in rats.OA was microinjected into the right lateral ventricle of male rats at a dose of 200 ng kg(-1) twice with a 3-day interval between injections to establish a model of Alzheimer's-disease-like cerebral damage. Neuronal morphology was observed with thionin staining and the expressions of glial fibrillary acidic protein (GFAP) and β-amyloid peptide 1-40 (Aβ1-40) were monitored via immunohistochemistry. The level of malondialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) were measured using spectrophotometry.The results showed that OA-treated rats exhibited marked neuronal damage accompanied by increased levels of Aβ1-40 peptide and MDA accumulation, decreased GFAP protein expression and reduced GSH-Px and LDH activity in the brain. SSF at three doses (25, 50 and 100 mg kg(-1)) dramatically reversed the OA-induced changes in the brains of rats.SSF-mediated amelioration of OA-induced neuronal damage in rats provides a rationale for assessing SSF as a means of to reducing tau hyperphosphorylation and Aβ expression in the treatment of Alzheimer's disease.

Previous studies reported that the total flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (TFSS) could enhance and improve learning and memory abilities in experimental animals, and reduce the neuronal pathologic alterations induced by some reagents in mice. The present study examined whether TFSS can improve memory dysfunction, neuronal damage, and abnormal free radicals induced by permanent cerebral ischemia in rats. The permanent cerebral ischemic model in rats was produced by bilateral ligation of the common carotid arteries. The influence of permanent cerebral ischemia on learning and memory was determined in the Morris water maze. The neuronal damage in the hippocampus and cerebral cortex was assessed by the neuronal morphologic observations. The contents of malondialdehyde (MDA) and nitric oxide (NO), and the activities of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and cerebral cortex were measured using thiobarbituric acid, nitrate reductase, xanthine-xanthine oxidase, and ammonium molybdate spectrophotometric methods, respectively. In learning and memory performance tests, cerebral ischemic rats always required a longer latency time to find the hidden platform and spent a shorter time in the target quadrant in the Morris water maze. TFSS 17.5-70 mg.kg(-1) daily orally administered to ischemic rats for 20 d, from day 16-35 after operation differently reduced the prolonged latency and increased swimming time spent in the target quadrant. In neuronal morphologic observations, daily oral TFSS 17.5-70 mg.kg(-1) for 21 d, from day 16-36 after operation markedly inhibited the ischemia-induced neuronal damage. In addition, the increased contents of MDA and NO, and SOD activity, and the decreased activity of CAT in the hippocampus and cerebral cortex induced by cerebral ischemia were differently reversed. The reference drug piracetam (140 mg.kg(-1) per day for 20-21 d) similarly improved impaired memory and neuronal damage but had no significant effects on free radicals in ligated rats. TFSS can improve memory deficits and neuronal damage in rats after permanent cerebral ischemia, which may be beneficial in the treatment of cerebrovascular dementia.

To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS.HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group).Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p 0.05).The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.

To study the effects of flavonoid, isolated from aerial parts of Scutellaria baicalensis Georgi (SSF), on memory impairment, neuronal damage, free radicals and energy metabolite disorders in aged rats.Approximately 25-month-old rats were used to establish the ageing model. The cognition of the rats was determined using the Morris water maze, neuronal morphology was observed by light/electron microscope, malondialdehyde (MDA) levels and the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and Na(+)-K(+)-ATPase were measured by spectrophotometry.In the Morris water maze task, the aged rats always took longer latency to find the hidden platform and spent less time swimming in the target quadrant than those of young control rats. The light/electron microscopic observations found significant neuropathological changes in the aged rats' brain. In addition, the production of MDA and the activity of SOD, LDH and Na(+)-K(+)-ATPase in the hippocampus and cerebral cortex of the aged rats showed critical abnormal changes. However, pre-treatment of the aged rats with SSF (35-140 mg kg(-1)) for 16-21 days dramatically improved cognitive dysfunction, neuropathological changes and biochemical abnormalities.These results indicate that the beneficial effects of SSF on memory impairment and neuronal damage in aged rats may be important for the treatment of senile dementia and for delaying the ageing processes.

Aim: There is increasing evidence indicating that embryonic stem (ES) cells are capable of differentiating into hepatocyte-like cells in vitro. However, it is necessary to improve the differentiation efficiency so as to promote the clinical application. Here, we report an efficient culture system to support hepatocyte differentiation from ES cells by utilizing cholestatic serum. Methods: One week after the induction of E14 mouse ES cells into hepatocytes with sodium butyrate, cholestatic serum was added into the culture system at various concentrations and hepatocyte-like cells were induced to proliferate. The morphological and phenotypic markers of hepatocytes were characterized using light microscopy, immunocytochemistry, and RT-PCR, respectively. The function of glycogen storage of the differentiated cells was detected by Periodic acid-Schiff (PAS) reaction, and the ratio of hepatic differentiation was determined by counting the albumin and PAS-positive cells. Results: In the presence of conditional selective medium containing cholestatic serum, numerous epithelial cells resembling hepatocytes were observed. The RT-PCR analysis showed that undifferentiated ES cells did not express any hepatic-specific markers; however, in the presence of sodium butyrate and conditional selective medium containing cholestatic serum, hepatic differentiation markers were detected. Immunofluorescence staining showed that those ES-derived hepatocytes were α-fetoprotein, albumin, and cytokeratin 18 positive, with the ability of storing glycogen. Further determination of the hepatic differentiation ratio showed that the application of cholestatic serum efficiently enriched ES-derived hepatocyte-like cells by inducing lineage differentiation and enhancing lineage proliferation. Conclusion: The conditional selective medium containing cholestatic serum is optimal to selectively enrich hepatocyte-like cells from mixed differentiated ES cells, which may provide a novel method to improve the hepatic differentiation ratio of ES cells.

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effects of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (SSF) against hydrogen peroxide (H2O2)-induced rat pheochromocytoma line PC12 injury were evaluated by cell lesion, free radicals and ATPase disorders. Following a 30 min exposure of the cells to H2O2 (100 microm), a marked decrease in cell survival and activity of superoxide dismutase (SOD) and Na+-K+-ATPase as well as an increase of malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. Pretreatment of the cells with SSF (18-76 microg/mL) prior to H2O2 exposure notably elevated the cell survival and activity of SOD and Na+-K+-ATPase, and lowered the MDA level and LDH release. Neuroprotection by SSF was also observed in animal models. The present results indicated that SSF exerts neuroprotective effects against H2O2 toxicity, which might be of importance and might contribute to its clinical efficacy for the treatment of neurodegenerative disease.

Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, an antioxidant, markedly improve memory impairments and neuronal injuries. In the present study, primary cortical neurons of rats were exposed to potassium cyanide to establish a model of in vitro neural cell apoptosis. Inhibition of apoptosis by flavonoids from the stems and leaves of Scutellaria baicalensis Georgi at concentrations of 18.98, 37.36, and 75.92 μg/mL was detected using this model. These flavonoids dramatically increased cell survival, inhibited cell apoptosis and excessive production of malondialdehyde, and increased the activities of superoxide dismutase, glutathione peroxidase, and Na(+)-K(+)-ATPase in primary cortical neurons exposed to potassium cyanide. The flavonoids from the stems and leaves of Scutellaria baicalensis Georgi were originally found to have a polyhydric structure and to protect against cerebral hypoxia in in vitro and in vivo models, including hypoxia induced by potassium cyanide or cerebral ischemia. The present study suggests that flavonoids from the stems and leaves of Scutellaria baicalensis Georgi exert neuroprotective effects via modulation of oxidative stress, such as malondialdehyde, superoxide dismutase, glutathione peroxidase and Na(+)-K(+)-ATPase disorders induced by potassium cyanide.