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Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer’s disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3β/GSK-3β proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3β/GSK-3β levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3β-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.

WeiHong Ren,1,2 XuRan Zhang,2 WenBo Li,2 Qian Feng,2 HuiJie Feng,2 Yan Tong,2 Hao Rong,2 Wei Wang,2 Dai Zhang,2 ZhenQiang Zhang,3 ShiChun Tu,4 XiaoYan Zhu,1 QinXian Zhang11Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 3Immunology Laboratory of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 4Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA, USABackground: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown.Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot.Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR-,CD33+,MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b+,Gr1+/high ,MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs.Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer.Keywords: exosome, miRNA-107, myeloid-derived suppressor cell, arginase 1, gastric cancer

Objectives: To measure the expression of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-2, and CD147 in mice with chronic liver injury induced by carbon tetrachloride after treatment with the traditional Chinese medicine (TCM) “Compound T11”. Method: Sixty male ICR mice were divided randomly into 6 groups of 10: control (C), model (M), low-dose treatment (LT; 50 mg/mL of Compound T11), medium-dose treatment (MT, 100 mg/mL), high-dose treatment (HT, 150 mg/mL), and positive drug treatment (YT, 67.5 mg/mL). Each group was modeled for 7 weeks. Groups M, LT, MT, HT, and YT were injected (s.c.) with 20% carbon tetrachloride diluted with olive oil, and group C was given olive oil in the same way twice a week. After modeling, the treatment groups were administered Compound T11 at the concentrations shown above by oral gavage daily for 2 weeks, while group C was given 0.5% carboxymethyl cellulose sodium. After the final treatment, mice were killed and their liver tissues were excised. Immunohistochemical staining was performed to measure the protein expression of MMP-2, TIMP-2, and CD147, and western blotting was used to measure the protein expression of MMP-2, TIMP-2, CD147, and α-smooth muscle actin (SMA). MMP-2, TIMP-2, and CD147 mRNA expression was determined by quantitative fluorescence real-time PCR. Results: Compound T11 increased the protein expression of MMP-2 and CD147 and decreased the protein expression of TIMP-2 and α-SMA. Conclusions: Treatment of chronic liver injury by TCM Compound T11 may be associated with changes to the expression of MMP-2 and CD147, and the inhibition of TIMP-2 expression.

Diabetes-related infections have become challenging and important public health problems in China and around the world. P. aeruginosa plays an important role in diabetic foot infections. As a gram-negative opportunistic pathogen, P. aeruginosa causes recurrent and refractory infections that are characterized by biofilm formation. Previous studies have demonstrated that biofilm-challenged wounds typically take longer to heal than non-biofilm-challenged normal wounds in diabetic mouse models. In the present study, we sought to explore the mechanism via which insulin treatment affects cyclic di-GMP signaling in P. aeruginosa-infected chronic wounds in db/db diabetic mice. We found that the wounds of diabetic mice healed more slowly than those of nondiabetic mice. Moreover, wound healing in diabetic mice treated with insulin exhibited a considerable delay. Peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) was used to detect biofilms on P. aeruginosa-infected wound tissues. Increased intracellular c-di-GMP levels promoted biofilm formation in wound tissues from nondiabetic mice. Greater biofilm formation was observed in the wounds of insulin-treated diabetic mice than in the wounds of untreated diabetic mice or nondiabetic mice, in both the PAO1/p(lac)-yhjH- and PAO1-infected groups. Quantitative RT-PCR indicated that upon infection with PAO1/P(lac)-yhjH (the low c-di-GMP expression strain), the expression of IL-4 RNA was significantly higher in diabetic mice treated with insulin than in untreated diabetic mice or nondiabetic mice at each observation time point. Peak expression of IFN-γ occurred earlier in diabetic mice treated with insulin than in untreated diabetic mice with each of the experimental strains. Finally, P. aeruginosa harboring the plasmid pCdrA: gfp (s) was used as a reporter strain to monitor c-di-GMP levels. We found that insulin could promote biofilm formation by increasing intracellular c-di-GMP levels in vitro. Taken together, these data demonstrate that insulin treatment increases intracellular c-di-GMP levels, promotes biofilm formation and prolongs the inflammation period during the healing of infected wounds, resulting in delayed wound healing.

Materials with opposite affinities toward oil and water have been extensively used to coat porous substrates for oil-water separation, but the applications of these materials have been limited by the need for complex coating processes as well as the short-term adherence of these materials onto different substrates under extreme conditions. As reported herein, the robust porous polyurethane hydrogel has been theoretically and structurally designed with ultralow-oil-adhesion properties which is free stand without depending on additional substrates. The combination of superhydrophilic properties along with the underwater superoleophobic behavior of this porous hydrogel allows gravity driven separations of oil-water mixtures, and its antiadhesion performance toward oil prevents undesirable oily fouling. The underwater superoleophobic properties were also illustrated by molecular dynamics simulation to understand the resisting effect of hydrated layers. The as-prepared porous hydrogel shows ultrahigh oil-water separation efficiencies of 99.9% for various oil-water mixtures, ranging from those containing viscous oils (pump oil and peanut oil) to organic solvents (n-hexane, n-hexadecane, and toluene). In addition, this hydrogel is durable even with exposure to various harsh conditions including acidic and basic media (pH 0-14) as well as exposure to mechanical abrasion. We believe that the combination of facile preparation, substrate independence, gravity driven separation, antifouling properties, high durability, as well as the outstanding separation flux and efficiency of this robust porous hydrogel will help to advance the design and application of materials in oil-water separation fields.

Yudi Ding, 1,* Nana Qi, 2,* Ke Wang, 1,* Yiming Huang, 2 Jinling Liao, 1 Hongxue Wang, 3 Aihua Tan, 3 Lihua Liu, 1 Zhenqiang Zhang, 1 Jinlong Li, 1 Jinliang Kong, 1 Shouming Qin, 1 Yonghua Jiang 2, 4, 5 1Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 4Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi 530021, People’s Republic of China; 5Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghua Jiang; Shouming Qin Tel +86 13978695898; +86 18275710900Email qinshouming2008@126.com; jiangyonghua@126.comBackground: The fat mass and obesity-associated protein (FTO) was identified as a critical demethylase involved in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues from mRNA. Emerging evidence has revealed that FTO is deeply implicated in lung cancer. However, knowledge of the function of FTO in lung adenocarcinoma (LUAC) is limited.Methods: FTO and FTO R96Q (R96Q), an FTO missense mutant lacking demethylase activity, were ectopically overexpressed, and FTO was knocked down via siRNA in A549 and H1299 cells. The relationships between FTO with cell characteristics and mRNA m6A levels were explored. Furthermore, RNA sequencing was performed on A549 cells.Results: FTO overexpression enhanced the proliferation, migration, and invasion ability of A549 and H1299 cells, decreased mRNA m6A levels. Interestingly, overexpression of R96Q, blunted the effects of FTO overexpression on cell proliferation and invasion. Through RNA sequencing analysis of A549 cells overexpressing FTO or R96Q and control A594 cells, 45 genes were identified as affected by m6A mRNA demethylation. Most of these genes were related to lung cancer, such as laminin γ 2, thrombospondin 1, nerve growth factor inducible, integrin alpha11, and proprotein convertase subtilisin/kexin type 9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that these genes are fundamental to cancer development processes, such as cell migration and extracellular matrix organization.Conclusion: Our research shows that FTO facilitates LUAC cell progression by activating cell migration through m6A demethylation; however, further research on the mechanism underlying FTO activity in LUAC is necessary.Keywords: FTO, lung adenocarcinoma, m6A demethylase

An experimental apparatus for simulation of continuous casting process of GCr15 bearing steel billet is established. With the apparatus, the billets of diameter 140 mm are casted in various...

In order to meet the demand of high-gain direct-current boost converter in the process of using new energy, a novel quadratic boost direct-current converter is proposed. In this paper, the quadratic boost direct-current converter compared to the traditional quadratic boost direct-current converter and boost circuit, have a higher voltage gain and lower switching tube voltage stress, which is more practical for high energy conversion efficiency , The voltage gain requirements of the new energy and network applications. The correctness of the theoretical analysis is proved by the experimental model of the laboratory.

The underwater superoleophobicity of a coating is often caused by its preferential water affinity, which, however, normally weakens the substrate adhesion property. In this work, a new strategy is reported for achieving strong underwater adhesion between a well-designed amphiphilic polyurethane coating and a diverse range of substrates while also rendering the coating surface's superoleophobicity. When the coating, which is a mixture of an amphiphilic polyurethane and a water miscible solvent, is immersed in water, the hydrophobic segments aggregate to orientate and pile along the surface of substrates via a segment orientation mechanism triggered by solvent exchange with water penetration to exert strong adhesion. At the same time, the hydrophilic segments will physically crosslink to form a hydrogel coating, endowing the substrate with underwater superoleophobicity. This work provides a facile, versatile, and scalable approach for the future design of superoleophobic coatings in a water environment.

In the process of smelting and manufacturing, bearing steel inevitably have defects such as non-metallic inclusions. Moreover, inclusion geometry (type, quantity, size, distribution, and shape) has a significant effect on the fatigue failure of bearing steel. In order to study effect extent of the size and distribution of inclusion on the fatigue life of bearings, this paper uses the test high-speed rail bearings LY-Z028 to research and analysis. The micro-model of contact between single inclusion and the matrix is established, and then performs ANSYS simulation on stress concentration which caused by size of single inclusion and relative surface depth. Further, multiple linear regression method is used to compare the effect extent of these two factors on the fatigue life. The results show that size of single inclusion has a greater impact on the fatigue life than relative surface depth, which can provide an effective reference for smelting and production requirements.

In this study, mature female mice of the ICR strain were induced to superovultate, mated, and collected at either zygote or early morula stages. Embryos suspended in 1 M ethylene glycol in PBS containing 10 mg/L Snomax for 15 min, then transferred in sample holder to Linkam cryostage, cooled to and seeded at 7 °C, and then observed and photographed while being cooled to −70 °C at 0.5–20 °C/min. Intracellular ice formation (IIF) was observed as abrupt ‘‘flashing’’. Two types of flashing or IIF were observed in this study. Extracellular freezing occurred at a mean of −7.7 °C. In morulae, about 25% turned dark within ±1 °C of extracellular ice formation (EIF). These we refer to as “high temperature’’ flashers. In zygotes, there were no high temperature flashers. All the zygotes flashed at temperatures well below the temperature for EIF. Presumably high temperature flashers were a consequence of membrane damage prior to EIF or damage from EIF. We shall not discuss them further. In the majority of cases, IIF occurred well below −7.7 °C; these we call ‘‘low temperature’’ flashers. None flashed with cooling rate (CR) of 0.5 °C/min in either zygotes or morulae. Nearly all flashed with CR of 4 °C/min or higher, but the distribution of temperatures is much broader with morulae than with zygotes. Also, the mean flashing temperature is much higher with morulae (−20.9 °C) than with zygotes (−40.3 °C). We computed the kinetics of water loss with respect to CR and temperature in both mouse zygotes and in morulae based on published estimates of Lp and it is Ea. The resulting dehydration curves combined with knowledge of the embryo nucleation temperature permits an estimate of the likelihood of IIF as a function of CR and subzero temperature. The agreement between these computed probabilities and the observed values are good.

With the rapid development of future grid technologies such as smart grid and energy internet, power electronic transformers with various functions such as voltage transformation, electrical isolation, power regulation and control, and renewable energy access can be realized. Relevant theories and technologies have been studied. More and more attention. However, from the overall point of view, the topology and design structure of the three major parts of the power electronic transformer (input stage, isolation stage, output stage) have great problems for the overall application. In this paper, the high-frequency transformer of the isolation stage is used in the middle of the power electronic transformer. The C-type nanocrystalline magnetic core is used to design the high-frequency transformer. The modeling of the transformer is completed in COMSOL, and the equivalent modeling of the winding is used to combine with the external circuit. The simulation analysis method is carried out and the high-frequency transformer is simulated and analyzed to study its feasibility.

The contact simulation model of high-speed railway train axle box bearing is simplified into a two-dimensional plane with an elastic semi-infinite body subjected to semi-elliptical cylindrical compressive stress in one direction. The ANSYS software was used to solve the effects of single inclusion size, the depth of the contact surface and the elastic modulus on dynamic shear stress and Von Mises stress of high-iron bearing subsurface, and compared with the calculation results of bearing material uniformity assumption. Using the modified Basquin equation, the relevant assumptions are made. The maximum Von Mises stress is used as the key stress for fatigue life calculation. The bearing fatigue life calculation method is established to study the influence of the inclusion size, the depth of the contact surface and the elastic modulus on the bearing fatigue life.

A solid model of a high-speed train axle box bearing was built by using 3D modeling software. On the platform of ANSYS/LS-DYNA, the combined dynamic and finite element analysis method is used to apply the combined radial and axial loads to the high-speed rail bearing. In order to demonstrate the dynamic contact characteristics of the bearing during operation, two operating conditions were designed. One is running at a uniform speed in a straight line, the other is running at an assumed speed with a minimum turning radius. The results show that the stress distribution, velocity and acceleration of bearing components under two different working conditions are obviously different. The research can provide reference for the design, selection and optimization of domestic high-speed rail bearings.

A mercury model has been developed to investigate the influences of Electromagnetic Mold Brake Ruler (EMBr-Ruler) and Flow Control Mold (FC-Mold) on metal flow in continuous casting of slab with the practical casting velocity 1.3 m/min. The experiment shows that the FC-Mold can efficiently repress the surface flow and its fluctuation. The expanding space of the pouring flow is compressed by EMBr-Ruler and FC-Mold respectively, then the ‘flow passage’ can be developed near the narrow wall of the mold, where the vertical velocity of flow will increase sharply. It is bad for the development of the plug like flow in the mold.

The porous Si-based ceramic core was prepared using injection method, where quartz glass powders were used as original materials and thermosetting silicon resin was used as plasticizer. The effect of sintering tem- perature and holding time on the properties of the samples were examined. It was found that the process of devitri- fication was accelerated with the increase of sintering temperature while the glass phase transforms into cristobalite gradually. When sintering temperature was at 1250℃, the amount of cristobalite increased with the extension of holding time. Linear shrinkage rate and weight loss of the samples slightly increased with the increase of sintering temperature. But the holding time showed less effect on linear shrinkage rate and weight loss of the samples. In fact, the weight loss of the sample was mainly caused by decomposition of silicon resin. The sample sintered at 1250 for ℃ 10 h showed linear shrinkage of 0.93%, the porosity of 32.8% and bending strength of 9.08 MPa.

In 2002, BGP successfully solved 3D long wavelength statics problems in a large area in Jiuquan Basin and several blocks in the Tarim Basin and Tuha Basin using tomographic inversion (TI). Recent years also saw the TI improvement in effectively solving 3D short wavelength statics problems. This paper discusses the processing sequence from first arrival (FA) picking to the model test, the methods behind the inversion and the relationship among them.