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In this paper, the dynamic stress intensity factor (DSIF) at the crack tip of a PMMA beam containing an internal offset crack under impact loading was investigated by using a transmission digital caustic test system combined with high-speed camera. Firstly, the stress intensity factor, as well as velocity, of the mixed-mode crack tip under static and dynamic loading were derived based on the transmission caustic method; secondly, a drop hammer loading test was conducted on the different specimens with biased cracks in the beam using the transmission caustic test system to obtain the dynamic fracture mechanics parameters of internal crack initiation and expansion; then, the crack initiation angle and expansion path analysis of the impact-generated expansion cracks were performed based on the theoretical analysis and the differences between the fracture process and that of the specimens containing internal symmetric cracks were discussed. The results show that the different locations of the internal off-set cracks make the stress redistribution process inside the beam and the stress state at the crack tip during the crack extension process different, and the fracture process and fracture mechanics parameters are different from those of the specimens with internal symmetric cracks, the results of the caustic test are in good agreement with the numerical analysis. The research results can provide guidance for the study of the fracture process of brittle materials such as PMMA containing internal defects.

Objectives] The study aims to explore the protective effect of Shenlingbaizhu powder on peroxidation injury and inflammatory response in mice with pneumonia. [Methods] 60 NIH mice were randomly divided into the blank group, model group, control group, large dose group, medium dose group and small dose group of Shenlingbaizhu powder. The mice in the control group were given cefixime granules, while the mice in each group of Shenlingbaizhu powder were given corresponding concentrations of Shenlingbaizhu powder water decoction by gavage. After 7 d, the content of MAD, SOD and CRP in the mice were detected by ELISA, while the content of NO was detected by fluorescence, and lung index was also detected. [Results] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [Conclusions] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the effect of Shenling Baizhu San combined with routine treatment on the clinical efficacy, gastrointestinal function protection, inflammatory response and immune function of children with bacterial pneumonia. [Methods] From July 2017 to January 2018, 80 children with bacterial pneumonia were randomly selected and divided into observation group and control group with 40 cases in each group. The control group was treated with conventional Western medicine, while the observation group was treated with Shenling Baizhu San on the basis of conventional treatment, with a period of 10 d. Then, we compared the clinical efficacy, incidence of gastrointestinal symptoms, WBC, CRP, CD4+ and CD8+ levels between the two groups. [Results] The clinical efficacy of the observation group was better than that of the control group（P<0.05）. After treatment, the levels of WBC and CRP in the two groups decreased, especially in the observation group（P<0.05）. After treatment, the level of CD4+ in both groups increased significantly, while the level of CD8+ decreased significantly, and the level of CD4+ in the observation group was significantly higher than that in the control group after treatment. The incidence of gastrointestinal symptoms in the observation group was significantly lower than that in the control group（P<0.01）. [Conclusions] Shenling Baizhu San can obviously improve the clinical effect of bacterial pneumonia in children and has the protective effect of gastrointestinal tract, and its mechanism may be related to its anti-inflammatory and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

From a variety of yield stress fluid models, an elastoviscoplastic Herschel-Bulkley (EVPHB) model written in 3D is selected and coupled with a Finite Element Method with Lagrangian Integration Points (FEMLIP) to solve boundary value problems with large deformation process. By tracing the historical variables of a material point, it is verified that in a time-independent flow the elastic strain and viscous strain rate could be accurately reproduced by EVPHB model. For a time-dependent flow, because of the addition of elasticity, the EVPHB model makes the material experience a deformation process which is significantly distinctive from that produced by a pure regularized Herschel-Bulkley model. Benchmarks also show that in FEMLIP the yielded and unyielded zones could be easily defined by EVPHB model according to the stress of a material point. Lastly, it is shown that EVPHB model also induces a stress relaxation process for materials under constant strain. The suitability of FEMLIP to model elastoviscoplastic fluid is verified.

The capillary component and adsorptive component of matric suction differently impact the soil strength. Due to the cavitation effects of pore water, the adsorption effect dominates the behavior of soil when matric suction exceeds the cavitation tension. Based on the binary medium theory, a compression-shear strength model for unsaturated soils considering both capillary effect and adsorption effect is established. Compared with test data, the proposed compression-shear strength model has better prediction performance on the compression-shear strength of soil over a range of wide suction. The soil failure depends both on tension-shear stress and compression-shear stress. The tension-shear coupling mechanism in the soil is first investigated. A concept of closed stress point is introduced to divide the two zones of tension-shear coupling stress and compression-shear stress. According to the compression-shear strength model and tension-shear failure mechanism, the tension-shear and compression-shear joint strength model applicable to plane stress conditions is then established. Compared with test data, the proposed model in this article can better predict the nonlinear strength characteristics of clays and has better applicability. Finally, using the user material subroutine (UMAT), the secondary development of the joint strength model is conducted in ABAQUS and then applied to the slope stability analysis. The calculation results show that the established strength model presents a reasonable description of the development of the tension-shear coupling plastic zone in slope and gives an accurate safety factor.

Paeonol (PAE) is a hydrophobic drug. In this study, we encapsulated paeonol in a lipid bilayer of liposomes (PAE-L), which delayed drug release and increased drug solubility. When PAE-L was dispersed in gels (PAE-L-G) based on a poloxamer matrix material for local transdermal delivery, we observed amphiphilicity, reversible thermal responsiveness, and micellar self-assembly behavior. These gels can be used for atopic dermatitis (AD), an inflammatory skin disease, to change the surface temperature of the skin. In this study, we prepared PAE-L-G at an appropriate temperature for the treatment of AD. We then assessed the gel’s relevant physicochemical properties, in vitro cumulative drug release, and antioxidant properties. We found that PAE-loaded liposomes could be designed to increase the drug effect of thermoreversible gels. At 32 °C, PAE-L-G could change from solution state to gelatinous state at 31.70 ± 0.42 s, while the viscosity was 136.98 ± 0.78 MPa.S and the free radical scavenging rates on DPPH and H2O2 were 92.24 ± 5.57% and 92.12 ± 2.71%, respectively. Drug release across the extracorporeal dialysis membrane reached 41.76 ± 3.78%. In AD-like mice, PAE-L-G could also relieve skin damage by the 12th day. In summary, PAE-L-G could play an antioxidant role and relieve inflammation caused by oxidative stress in AD.

Flexible conductive hydrogel has been driven by scientific breakthroughs and offers a wide variety of applications, including sensors, electronic skins, biomedicine, energy storage, etc. Based on the mixed-ion crosslinking method, gelatin and sodium alginate (Gel–Alg) composite hydrogels were successfully prepared using Ca2+ crosslinking. The migration behavior of berberine hydrochloride (BBH) in the matrix network structure of Gel–Alg hydrogel with a certain pore size under an electric field was studied, and the transdermal effect of berberine hydrochloride under an electric field was also studied. The experimental results show that Gel–Alg has good flexibility and conductivity, and electrical stimulation can enhance the transdermal effect of drugs. Gel–Alg composite hydrogel may be a new material with potential application value in future biomedical directions.

Long-term sunlight exposure will cause the accumulation of free radicals in the skin and lead to oxidative damage and aging, antioxidant drugs have gradually become the focus of research, but there is little research on antioxidant drugs for percutaneous treatment. The purpose of this study was to prepare ligustrazine hydrochloride (TMPZ)-loaded liposome–hydrogel (TMPZ-LG), evaluate its antioxidant properties, and apply it on the skin of mice to observe whether it had preventive and therapeutic effect on the irradiation under the ultraviolet rays, in an attempt to make it into a new kind of delivery through the skin. TMPZ-LG was prepared by the combination of film dispersion and sodium carboxymethylcellulose (2%, CMC-Na) natural swelling method. The release rates in vitro permeation across the dialysis membrane and ex vivo transdermal had both reached 40%; the scavenging effect of TMPZ-LG on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2 were 65.57 ± 4.13% and 73.06 ± 5.65%; the inhibition rate of TMPZ-LG on malondialdehyde (MDA) production in liver homogenate and anti-low density lipoprotein (LDL) oxidation experiments ex vivo were 15.03 ± 0.9% and 21.57 ± 1.2%. Compared with untreated mice, the skin pathological symptoms of mice coated with TMPZ-LG were significantly reduced after ultraviolet irradiation, and there was statistical significance. The results showed TMPZ-LG could exert good antioxidant activity in vitro and ex vivo; therefore, it is feasible to prevent and treat skin oxidation.

In electrical substations, glass-fibre reinforced polymer (GFRP) insulators provide an alternative to porcelain insulators for better seismic performance. The bonded connection between the composite tube and the metal end fitting is a weak link under earthquake actions, and the failure risk of ultra-high voltage (UHV) substation equipment with GFRP composite insulators can be considerable in places with high seismicity. This study solved the problem by retrofitting and experimentally qualifying the seismic performance of surge arresters made of composite insulators. To ensure safety under a bending moment corresponding to the seismic demand, the bonded sleeve joint between the tube and end fitting was retrofitted by shear stiffeners and higher strength end fitting. A full-scale shaking table test was carried out to verify the performance of the retrofitted surge arrester, and the seismic responses to increasing earthquake actions were analyzed. The specimens in this study were full-scale, had the largest dimensions among substation equipment of the same type, and were subjected to an extremely high earthquake action of 0.5 g; therefore, the seismic testing results produced in this study can serve as an important reference for the industry.

Docetaxel (DTX)-based formulation development is still confronted with significant challenges, due to its refractory solubility and side effects on normal tissues. Inspired by the application of the transdermal drug delivery model to topical treatment, we developed a biocompatible and slow-release DTX-containing emulsion via self-assembly prepared by a high-speed electric stirring method and optimized the formulation. The results of accelerated the emulsion stability experiment showed that the emulsion prepared at 10,000 rpm/min had a stability of 89.15 ± 2.05%. The ADME, skin irritation, skin toxicity and molecular interaction between DTX and excipients were predicted via Discovery Studio 2016 software. In addition, DTX addition in oil or water phases of the emulsion showed different release rates in vitro and ex vivo. The DTX release ex vivo of the DTX/O-containing emulsion and the DTX/W-containing emulsion were 45.07 ± 5.41% and 96.48 ± 4.54%, respectively. In vitro antioxidant assays and anti-lipid peroxidation models revealed the antioxidant potential of DTX. However, DTX-containing emulsions could maintain and even enhance the antioxidant effect, both scavenging free radicals in vitro and inhibiting the process of lipid peroxidation.

The purpose of this study was to prepare and evaluate kaempferol-loaded carbopol polymer (acrylic acid) hydrogel, investigate its antioxidant activity in vitro, and compare the effects on drug release under different pH conditions. Drug release studies were conducted in three different pH media (pH 3.4, 5.4, and 7.4). The kaempferol-loaded hydrogel was prepared by using carbopol 934 as the hydrogel matrix. The morphology and viscosity of the preparation were tested to understand the fluidity of the hydrogel. The antioxidant activity of the preparation was studied by scavenging hydrogen peroxide and 2,2-diphenyl-1-picrilhidrazil (DPPH) radicals in vitro and inhibiting the production of malondialdehyde in mouse tissues. The results showed that kaempferol and its preparations had high antioxidant activity. In vitro release studies showed that the drug release at pH 3.4, 5.4, and 7.4 was 27.32 ± 3.49%, 70.89 ± 8.91%, and 87.9 ± 10.13%, respectively. Kaempferol-loaded carbopol hydrogel displayed greater swelling and drug release at higher pH values (pH 7.4).

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. [ABSTRACT FROM AUTHOR]

In order to consider the influence of nonlinear characteristics of porcelain pillar electrical equipment on the dynamic response under seismic excitation, a theoretical analysis method of nonlinear dynamics was raised to define the nonlinear parameter of the flange connection and establish a dynamic model of porcelain pillar electrical equipment. The theoretical analysis and the test results have a good degree of fitting, which verifies the correctness of the dynamic model and reveals the nonlinear seismic response law of the porcelain pillar equipment. According to the results, both the nonlinear calculation results of the displacement at the top end of the porcelain pillar and the stress at the bottom end of the porcelain pillar are smaller than the results in the linear calculation. The difference between them increases gradually with the increase of seismic excitation. The differences in displacement and stress at a seismic excitation of 0.5 g are 14.58% and 23.25%, respectively. When the nonlinear parameter increases to a certain value, the impact of maximum stress on the bottom of the porcelain pillar is very small and the change is not obvious. The research provides a theoretical reference for the seismic design of pillar electrical equipment.

Frequent earthquakes in strong earthquake areas pose a great threat to the safety operation of electric power facilities. There exists a pressing research need to develop an assessment method for the seismic risk of substations, i.e., the hubs of power system networks. In this study, based on Incremental Dynamic Analysis (IDA), Probabilistic Seismic Demand Model (PSDM) and reliability theory, a vulnerability model for a substation is obtained, based on considering the relationships between Peak Ground Acceleration (PGA) and four seismic damage states (complete, extensive, moderate, and slight.) via a probabilistic approach. After an earthquake, the scope of influence and PGA distribution are evaluated using information recorded by the seismic observation stations, based on using interpolation or an empirical formula for the PGA attenuation. Therefore, the seismic risk can be evaluated by combining ground motion evaluation and the pre-built vulnerability model. The Wuqia- Kashgar area of Xinjiang was selected as the study area; it is an Earthquake-prone area, and one of the starting points for new energy transmission projects in China. Under a hypothetical earthquake (MS 7.9), the seismic risk of the substations was evaluated. The results show that: this method is able to give the probabilities of the four damage states of the substations, four substations close to the epicenter only have a probability of slight damage (45%-88%) and other substations are safer.

In order to analyze the uplift bearing capacity of transmission tower foundation in the geosythetic-reinforced aeolian sand, a series of simplified indoor modeling tests are carried out. A simplified reduced-scale foundation made according to the prototype and the uplift bearing capacity of transmission tower foundation in geosynthetic-reinforced aeolian sand is studied. Three kinds of reinforcement materials are embedded in the sand according to five ways of layout spacing. A total of 15 reinforcement schemes are tested. The results show that ultimate uplift bearing capacity of transmission tower foundation can be significantly improved by the reinforcement treatment of geotechnical materials in the aeolian sand. The type and spacing of reinforced materials also have a significant influence on the uplift bearing capacity of the foundation model in reinforced aeolian sand, and the effect of reinforcement works until the end of the loading process. The comprehensive effect is evaluated by the ratio of bearing capacity improvement and the total layer of reinforced materials. Based on the above results, the bearing mechanism of transmission tower foundation in geosynthetic-reinforced aeolian sand is elaborated and analyzed in detail.

Pillar electrical equipment is an important part of substations. The application of composite materials in pillar equipment can facilitate the improvement of the seismic performance of electrical equipment. In this paper, the test of elastic modulus and bending rigidity was conducted for individual composite elements in insulators and arresters, and the calculation formula for bending rigidity at the composite flange cementing connections was put forward. The numerical simulation model for the earthquake simulation shaking table test of ±1,100 kV composite pillar insulators was established, in which the bending rigidity value for the flange cementing part was obtained by the test or calculation formula. The numerical simulation results were compared with the earthquake simulation shaking table test results, the dynamic characteristics and seismic response of the model were compared, respectively, the validity of the proposed calculation formula for flange bending rigidity of composite cementing parts was verified, and a convenient and effective means was provided for calculating the seismic performance of composite electrical equipment.

When the finite element-strength reduction method is used for two-dimensional slope stability analysis for elastic-perfectly plastic material, the failure criterion usually adopts the criterion of plastic zone penetration. That is, when the slope is in the limit equilibrium state, the plastic zone goes through the slope from the toe to the top. Meanwhile, the critical slip surface is composed of a series of points of maximum equivalent plastic strain along the depth direction. By deploying a set of parallel lines approximately perpendicular to the slope surface and picking out the points of these lines with the maximum equivalent strain points, we obtain a series of points taking on a wave shape, which constitutes a signal function. Subsequently, the wavelet packet analysis is used to smooth these points, i.e., locating the critical slip surface. The analysis of classic examples and comparison with Spencer’s method show that the proposed method in this paper is reasonable and effective.

Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the intermediate zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin-mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription. [ABSTRACT FROM AUTHOR]

Accumulation of senile plaques composed of amyloid β-peptide (Aβ) is a pathological hallmark of Alzheimer disease (AD), and Aβ is generated through the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase. Although oxidative stress has been implicated in the AD pathogenesis by inducing Aβ production, the underlying mechanism remains elusive. Here we show that the pro-oxidant H2O2 promotes Aβ production through c-Jun N-terminal kinase (JNK)-dependent activation of γ-secretase. Treatment with H2O2 induced significant increase in the levels of intracellular and secreted Aβ in human neuroblastoma SH-SY5Y cells. Although γ-secretase-mediated cleavage of APP or C99 was enhanced upon H2O2 treatment, expression of APP or its α/β-secretase-mediated cleavage was not affected. Silencing of the stress-activated JNK by small interfering RNA or the specific JNK inhibitor SP600125 reduced H2O2-induced γ-secretase-mediated cleavage of APP. JNK activity was augmented in human brain tissues from AD patients and active JNK located surrounding the senile plaques in the brain of AD model mouse. Our data suggest that oxidative stress-activated JNK may contribute to senile plaque expansion through the promotion of γ-secretase-mediated APP cleavage and Aβ production. [ABSTRACT FROM AUTHOR]

Leady isolator shows hysteretic nonlinearity. The isolation efficiency of leady isolator is an important problem in many engineering structures. In this paper, vibrations of a ceramic upright pole coupled with four leady isolators under harmonic base excitation are studied. A hysteretic force-deformation model of leady isolator is derived from experimental results. With this model, the vibration of the pole in rotation is studied. The frequency response is obtained analytically by employing harmonic balance method. The analytical results are agreed well with numerical results. The vibration of the pole is decreased greatly by leady isolator, especially near resonant case. The influences of system parameters on vibration response and resonant peak are discussed in detail.

Retinoic acid (RA), a metabolite of retinol, is one of the most biologically active forms of retinoid and plays vital roles in embryonic development and in the regulation of cell proliferation and differentiation. Knowing that liposomes simulate cell membranes and that hydrogel is an ideal delivery vehicle for topical medicine, liposome-hydrogel is a novel preparation that has synergistic advantages over each component separately. Our objective was to investigate the characteristics of RA liposome-hydrogel. For quality control of the RA-loaded liposomes, we measured their morphology, particle size, Zeta-potential, and entrapment efficiency. Then we determined the viscosity of RA liposome-hydrogel. Next, the diffusion through mouse skin was explored, followed by investigation of the mRNA expression levels of Ker18, REX1, and α-FP using Q-PCR. The results showed that RA liposome-hydrogel penetrates the mouse skin effectively. The permeation rates were: Qn (%) of RA liposome-hydrogel < Qn(%) of RA-loaded liposome < Qn (%) of RA. The mRNA expression levels were dose-dependent and the effective dose decreased between vehicles due to their different release rates. F9 mouse teratocarcinoma stem cells were an ideal model to explore the mechanism of RA liposome-hydrogel in stem cell differentiation.

During early embryonic development, bone morphogenetic protein (BMP) signaling is essential for neural/non-neural cell fate decisions. BMP signaling inhibits precocious neural differentiation and allows for proper differentiation of mesoderm, endoderm, and epidermis. However, the mechanisms underlying theBMPpathway-mediated cell fate decision remain largely unknown. Here, we show that the expression of Ovol2, which encodes an evolutionarily conserved zinc finger transcription factor, is down-regulated during neural differentiation of mouse embryonic stem cells. Knockdown of Ovol2 in embryonic stem cells facilitates neural conversion and inhibits mesendodermal differentiation, whereas Ovol2 overexpression gives rise to the opposite phenotype. Moreover, Ovol2 knockdown partially rescues the neural inhibition and mesendodermal induction by BMP4. Mechanistic studies further show that BMP4 directly regulates Ovol2 expression through the binding of Smad1/5/8 to the second intron of the Ovol2 gene. In the chick embryo, cOvol2 expression is specifically excluded from neural territory and is up-regulated by BMP4. In addition, ectopic expression of cOvol2 in the prospective neural plate represses the expression of the definitive neural plate marker cSox2. Taken together, these results indicate that Ovol2 acts downstream of the BMP pathway in the cell fate decision between neuroectoderm and mesendoderm to ensure proper germ layer development. [ABSTRACT FROM AUTHOR]