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The outbreak of COVID-19 epidemic has enabled the establishment and application of various rapid detection methods. It is particularly important to establish a fast and accurate detection method for enterovirus, which will be beneficial for clinical diagnosis, epidemic prevention and control, and timely traceability. Through establishing an ultra-fast reverse transcription-polymerase chain reaction (RT-PCR) equipment, this study aimed to evaluate the sensitivity and specificity of the testing method of enterovirus nucleic acids based on ultra-fast real-time fluorescence RT-PCR technology. A total of 61 cases were sampled, which were then transported and preserved. After the nucleic acid extraction, the nucleic acids of the same sample were tested with the enterovirus nucleic acid detection kit produced by Guangzhou Da An Gene Company and the ultra-fast RT-PCR equipment system established in this study. ABI7500Fast and Ahram biosystems S1 fast equipment were used for amplification detection. If the sample had an S-shaped amplification curve in the FAM channel and the Ct value ≤40.00, the result was positive. The sensitivity, precision, and accuracy of the detection method were then verified. This study established a novel testing method to achieve enterovirus nucleic acid detection within 24 min. The sensitivity detection limit of the method was 1.0 × 10

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor prevalent in southern China and Southeast Asia. Previous studies have shown that Kinesin Family Member 3A (KIF3A) plays a critical role in the oncogenesis of various cancer types. However, the role of KIF3A in NPC tumorigenesis and the mechanism underlying its function have not been reported. In this study, we found that KIF3A was significantly downregulated in NPC cells and tissues, and KIF3A expression in NPC patients was associated with tumor stage and was positively corrected with overall survival. In vitro and in vivo experiments indicated that overexpression of KIF3A inhibited NPC cell proliferation, migration, and invasion. Mechanistic studies found that KIF3A bound β-catenin and attenuated β-catenin aggregation in the nucleus. Moreover, rescue experiments demonstrated that the inhibitory effect of KIF3A on NPC proliferation, migration and invasion was partially dependent on β-catenin. Taken together, our data suggest that KIF3A interacts with β-catenin and attenuates NPC proliferation, migration, and invasion by suppressing the intranuclear aggregation of β-catenin. KIF3A may be a promising therapeutic target of patients with NPC.

Background Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats. Methods Learning and memory were measured using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms. Results The results indicated that LGG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFAs levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by LGG intervention. Conclusions Taken together, LGG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Background Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumour that is prevalent in Southern China and other Southeast Asian countries. In previous studies, Kinesin Family Member 3A (KIF3A) was shown to play a dual role in cancers. However, the biological role of KIF3A in NPC and the underlying mechanism have not been reported. Methods The KIF3A mRNA and protein expressions in NPC were analyzed by qRT-PCR (Quantitative real-time polymerase chain reaction), Western blotting and immunohistochemistry. CCK-8, EDU incorporation assay, Colony formation, cell cycle assay, Wound-Healing Assay, Transwell verified KIF3A regulates the proliferation, migration, invasion of NPC cells. The in vivo effect of KIF3A on proliferation was elucidated with a xenograft mouse model. COIP (Co-immunoprecipitation) assay showed KIF3A interacts with β-catenin. Confocal microscopy colocalization assay confirmed colocalization of KIF3A and β-catenin in NPC cells. Nuclear and cytoplasmic extraction assays were performed to analyze the distribution of β-catenin in the nuclei and cytoplasm. Results In this study, we found that KIF3A interacts with β-catenin, suppressing the intranuclear aggregation of β-catenin, then inactivating the Wnt/β-catenin signaling pathway as well as the downstream cell cycle factors and EMT signal to inhibit NPC proliferation, migration, and invasion. Conclusions These findings suggest that KIF3A interacts with β-catenin and attenuates the malignant progression of NPC by inhibiting β-catenin intranuclear aggregation. KIF3A may be a promising therapeutic target for NPC patients.

One of the primary goals of the Consortium for the Advancement of Shape Memory Alloy Research and Technology is to enable the design of revolutionary applications based on shape memory alloy technology. To advance this goal and reduce the development time and required experience for the fabrication of shape memory alloy actuation systems, several modeling tools were developed for common actuator types and are discussed along with case studies, which highlight their capabilities and limitations. Shape memory alloys have many potential applications as reliable, lightweight, solid-state actuators given their ability to sustain high stresses and recover large deformations. In this article, modeling frameworks are developed for three common actuator designs: wires, lightweight, low-profile, and easily implemented; coiled springs, offering actuation strokes upward of 200% at reduced mechanical loads; and torque tubes, which can provide large actuation torques in small volumes and repeatable low-load actuation. Although the design and integration of a shape memory alloy–based actuation system requires application- and environment-specific engineering considerations, common modeling tools can significantly reduce the investment required for actuation system development and provide valuable engineering insight. This analysis presents a collection of Consortium for the Advancement of Shape Memory Alloy Research and Technology collaborative best practices to allow readers to utilize the available design tools and understand their modeling principles.

Ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) is one of the deubiquitinating enzymes in the ubiquitin-proteasome system. It has been shown that UCH-L1 could markedly decrease neointima formation through suppressing vascular smooth muscle cell (VSMC) proliferation in the balloon-injured rat carotid. However, whether UCH-L1 plays roles in VSMC migration remains to be determined. In this study, the primary VSMCs were isolated from aortic media of rats and TNF-α to was used to induce VSMC migration. Using a modified Boyden chamber and wound healing assay, it was found that TNF-α can dose and time-dependently induce VSMC migration with a maximal effect at 10 ng/mL. Moreover, UCH-L1 expression increased gradually with the prolonged induction time at 10 ng/mL of TNF-α. UCH-L1 content in VSMC was then modulated by recombinant adenoviruses expressing UCH-L1 or RNA interference to evaluate its roles in cell migration. The results showed that over-expression of UCH-L1 attenuated VSMC migration, while knockdown of it enhanced cell migration significantly no matter whether TNF-α treatment or not. Finally, the effect of UCH-L1 on NF-κB activation was demonstrated by NF-κB nuclear translocation and DNA binding activity, and the levels of IL-6 and IL-8 in cell culture media were examined by ELISA. It was showed that UCH-L1 over-expression inhibited NF-κB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-κB activation and increase IL-6 and IL-8 levels during TNF-α treatment. These data suggest that UCH-L1 can inhibit TNF-α-induced VSMCs migration, and this kind of effect may partially due to its suppression role in NF-κB activation.

Neural interface is a critical component for the communication between the central nervous system and outside devices. But neural tissues withstand constant mechanical activity with outside devices...

Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer’s disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

Automotive battery manufacturers are working to improve individual cell and overall pack design by increasing their safety, performance, durability, and range, while reducing cost; and active material volume change is one of the more complex aspects that needs to be considered during this process. In the study shown here, thermodynamically non-ideal, lithiation-based volume change behavior for the anode and cathode active materials were incorporated into a previously developed mechano-electrochemical model. The changing thickness of an automotive-relevant, large-format pouch cell was predicted while simulating cell discharge. Measurements were taken using an experimental setup capable of simultaneous mechanical and electrochemical operation and observation. The electrochemical and mechanical measurements prove to agree well with simulation when using non-ideal lithiation-based volume change as opposed to the previously assumed ideal volume change behavior. The resulting model was used to simulate other mechano-electrochemical phenomena including the effects of anode/cathode capacity ratio and changing pressure/porosity during cell discharge. This mechano-electrochemical model shows promise to help define operational parameters to mitigate negative effects from active material volume change and may act as a tool for developers reduce the extensive electrochemical and mechanical testing required for the design of promising new batteries.

Background Zika virus (ZIKV) had spread rapidly in the past few years in southern hemisphere where dengue virus (DENV) had caused epidemic problems for over half a century. The high degree of cross-reactivity of Envelope (E) protein specific antibody responses between ZIKV and DENV made it challenging to perform differential diagnosis between the two infections using standard ELISA method for E protein. Methods Using an IgG capture ELISA, we investigated the kinetics of nonstructural protein 1 (NS1) antibody response during natural ZIKV infection and the cross-reactivity to NS1 proteins using convalescent sera obtained from patients infected by either DENV or ZIKV. Results The analyses of the sequential serum samples from ZIKV infected individuals showed NS1 specific Abs appeared 2 weeks later than E specific Abs. Notably, human sera from ZIKV infected individuals did not contain cross-reactivity to NS1 proteins of any of the four DENV serotypes. Furthermore, four out of five NS1-specific monoclonal antibodies (mAbs) isolated from ZIKV infected individuals did not bind to DENV NS1 proteins. Only limited amount of cross-reactivity to ZIKV NS1 was displayed in 108 DENV1 immune sera at 1:100 dilution. Conclusions The high degree of NS1-specific Abs in both ZIKV and DENV infection revealed here suggest that NS1-based diagnostics would significantly improve the differential diagnosis between DENV and ZIKV infections. Electronic supplementary material The online version of this article (10.1186/s12879-018-3173-y) contains supplementary material, which is available to authorized users.

Stress-induced cardiomyocyte apoptosis plays an important role in the pathogenesis of a variety of cardiovascular diseases. Our early studies showed that HSP70 effectively inhibited apoptosis, but the underlying mechanism remained unclear. Fas-associated factor 1 (FAF1) is a member of the Fas death-inducing signaling complex (Fas-DISC) that acts upstream of caspase-8. We investigated the interactions among FAF1, HSP70, and FAS in stressed cardiomyocytes to elucidate the protective mechanism of HSP70. FAS and caspase-3/8 activity was higher in cardiomyocytes undergoing stress-induced apoptosis in restraint-stressed rats compared with cardiomyocytes in non-stressed rats, which indicated that the Fas signaling pathway was activated after restraint stress. Geranylgeranylacetone (GGA) induced an increase in HSP70 expression, which reduced stress-induced apoptosis. Additionally, overexpression of HSP70 via transfection with the pEGFP-rHSP70 plasmid attenuated norepinephrine (NE)-induced apoptosis. FAF1 expression increased during stress-induced apoptosis, and overexpression of FAF1 exacerbated NE-induced apoptosis. We also found that HSP70 interacted with FAF1. Overexpression of HSP70 inhibited the binding of FAF1 to FAS in H9C2 cells, which indicated that HSP70 suppressed NE-induced apoptosis by competitively binding to FAF1. An N-terminal deletion mutant of HSP70 (HSP70-△N) was unable to interact with FAF1. After HSP70-△N was transfected into H9C2 cells, the cells were unable to attenuate the NE-induced increases in caspase-8 and apoptosis. These results indicate that the 1–120 sequence of HSP70 binds to FAF1, which alters the interactions between FAS and FAF1 and inhibits the activation of the Fas signaling pathway and apoptosis.

Fibrosis is an important, structurally damaging event that occurs in pathological cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in pressure overload-induced heart failure and has been reported to play an important role in cardiomyocyte apoptosis; however, its involvement in cardiac fibroblasts (CFs) remains unknown. We prove for the first time that the expression of BNIP3L is significantly increased in the CFs of rats undergoing pressure overload-induced heart failure. Furthermore, this increased BNIP3L expression was confirmed in cultured neonatal rat CFs undergoing proliferation and extracellular matrix (ECM) protein over-expression that was induced by norepinephrine (NE). The overexpression or suppression of BNIP3L promoted or inhibited NE-induced proliferation and ECM expression in CFs, respectively. In addition, [Ca2+]i, transforming growth factor beta (TGF-β) and the nuclear accumulation of Smad2/3 were successively increased when BNIP3L was overexpressed and reduced when BNIP3L was inhibited. Furthermore, the down-regulation of TGF-β by TGF-β-siRNA attenuated the increase of BNIP3L-induced fibronectin expression. We also demonstrated that the increase of BNIP3L in CFs was regulated by NE-AR-PKC pathway in vitro and in vivo. These results reveal that BNIP3L is a novel mediator of pressure overload-induced cardiac fibrosis through the [Ca2+]i-TGF-β-Smad2/3 pathway in CFs.

The EF-hand calcium-binding protein S100B presents a wide range of biological activities and functions. This binding protein is involved in various human diseases, including cancer, brain trauma and ischemia, neuro-degenerative disease (Alzheimer's disease), and psychiatric disorders. In this study, we prepared human S100B protein and its monoclonal antibodies. Human S100B protein was expressed in Escherichia coli, successfully purified by diethylaminoethyl cellulose anion-exchange chromatography, and then identified by western blot analysis. Monoclonal antibodies (mAbs) were produced by the standard hybridoma method and validated by enzyme-linked immunosorbent assay and western blot analysis. The prepared human S100B protein and its mAbs demonstrated potential biological activities. The KD of one mAb is approximately 4.72x10-8 mol/l, and its cross reactivity is low with human S100A4, mouse S100A4, and human S100A1. Recombinant Soluble S100B can promote the migration and invasion of HeLa cells. The expression of S100B protein in tumor tissues can be detected effectively by using the prepared monoclonal antibodies. Increasing concentration of the anti-human S100B mAbs showed a reduced expression of the S100B protein. Subsequently, the expression of p53 increased significantly (P

Introduction Myocardial hypertrophy is an adaptive response of the heart to work overload. Pathological cardiac hypertrophy is usually associated with the ultimate development of cardiac dysfunction and heart failure. The mitochondria have an important function in the development of cardiac hypertrophy. However, mitochondrial adaptations to hypertrophic stimulus remain ambiguous. Methods A rat model of myocardial hypertrophy was established using abdominal aortic constriction. The expression of mitochondrial complexes was evaluated through electrophoresis using blue native and blue native/sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme activity of mitochondrial complexes was detected through in-gel activity. Results Mitochondrial function and biogenesis decreased in hypertrophied myocardium. The content and activity of mitochondrial Complex V dimers and Complex I significantly decreased during hypertrophy, as well as those of the α, β, B, and D chains of the Complex V dimers. However, the content and activity of mitochondrial Complex V oligomers and Complexes II, III, and IV did not change. Conclusions The decreased content and activity of Complex V dimers and Complex I caused the decline in mitochondrial function and biogenesis during cardiac hypertrophy.

Fibrosis is an important, structurally damaging event that occurs in pathological cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in pressure overload-induced heart failure and has been reported to play an important role in cardiomyocyte apoptosis; however, its involvement in cardiac fibroblasts (CFs) remains unknown. We prove for the first time that the expression of BNIP3L is significantly increased in the CFs of rats undergoing pressure overload-induced heart failure. Furthermore, this increased BNIP3L expression was confirmed in cultured neonatal rat CFs undergoing proliferation and extracellular matrix (ECM) protein over-expression that was induced by norepinephrine (NE). The overexpression or suppression of BNIP3L promoted or inhibited NE-induced proliferation and ECM expression in CFs, respectively. In addition, [Ca2+]i, transforming growth factor beta (TGF-β) and the nuclear accumulation of Smad2/3 were successively increased when BNIP3L was overexpressed and reduced when BNIP3L was inhibited. Furthermore, the down-regulation of TGF-β by TGF-β-siRNA attenuated the increase of BNIP3L-induced fibronectin expression. We also demonstrated that the increase of BNIP3L in CFs was regulated by NE-AR-PKC pathway in vitro and in vivo. These results reveal that BNIP3L is a novel mediator of pressure overload-induced cardiac fibrosis through the [Ca2+]i-TGF-β-Smad2/3 pathway in CFs.

Hyperhomocysteinemia (HHcy), a pathological condition characterized by an increase in plasma concentration of total homocysteine (Hcy), is recognized as a risk factor for several diseases. The transsulfuration pathway is the main metabolic fate of Hcy utilization, which requires the activity of cystathionine β-synthase (CBS). Our results showed the development of HHcy induced by psychological stress was mainly derived from a reduction of CBS activity in the liver, which was accompanied by a significant decrease in its mRNA level. It suggested that the hepatic CBS enzyme regulated by stress at the level of transcription would have a profound effect on circulating Hcy levels. The expression of Sp3, a negative factor for cbs transcription, obviously increased in hepatocytes nuclei of stressed rats, but Sp1 was not altered. It indicated that Sp3 was the key point of variations in cbs transcription caused by stress. Meanwhile, we detected that augmented plasma Hcy concentrations correlated with glucocordicoids (GCs) over-secretion in response to stress, and CBS mRNA levels were markedly lowered in GCs-treated rat hepatocytes. Further results found that glucocorticoids receptor (GR) expression in hepatocyte nuclei of stress rats and GR nuclear translocation ratio was increased, and the same results were proved by experiments in vitro, i.e., GR nuclear translocation and Sp3 expression was remarkably increased in GCs-treated hepatocytes. Moreover, results from ChIP suggested GCs enhanced the binding of GR to the regulatory region of the Sp3 promoter. These results indicated that GCs inhibit CBS transcription by up-regulating Sp3 in psychological stress-induced HHcy.

Although previous studies have shown that autoantigens such as Hsps have been implicated by induction of an autoimmune process in the development of atherosclerosis, the exact role of anti-Hsp70 antibody in atherosclerosis is unknown. In the present study, the levels of anti-Hsp70 autoantibodies and oxidized low density lipoprotein (OxLDL) were all significantly increased, and they were strongly correlated in an atherosclerosis model. After the endothelial cells were incubated with 20 μg/mL OxLDL for 12 h at 37 °C and followed by 90 min recovery, Hsp70 positive staining of OxLDL-treated endothelial cells was observed on the cell surface in immunostaining and flow cytometric analysis. This membrane Hsp70 was not from culture supernatant Hsp70 and binding of extracellular Hsp70 but was defined as endothelial surface membrane Hsp70. Furthermore, only in the OxLDL-treated group, but not in the untreated group, (51)Cr-labeled endothelial cells were lysed by anti-Hsp70 antibody (BD091, Ig(AS)) in the presence of either complement or peripheral blood mononuclear cells. Control antibodies, including Ig(Nor), mAb to Hsp70 (SPA-810), and mAbs to Factor VIII, α-actin, and CD3 showed no cytotoxic effects. In conclusion, anti-Hsp70 antibodies could be reacting with the endothelial surface membrane Hsp70 induced by OxLDL and were able to mediate endothelial cytotoxicity. There is a possibility that a humoral immune reaction to endothelial surface membrane Hsp70 may play an important role in the pathogenesis of atherosclerosis.

The primary goal of the Consortium for the Advancement of Shape Memory Alloy Research and Technology (CASMART) is to enable the design of revolutionary applications based on shape memory alloy (SMA) technology. In order to help realize this goal and reduce the development time and required experience for the fabrication of SMA actuation systems, several modeling tools have been developed for common actuator types and are discussed herein along with case studies, which highlight the capabilities and limitations of these tools. Due to their ability to sustain high stresses and recover large deformations, SMAs have many potential applications as reliable, lightweight, solid-state actuators. Their advantage over classical actuators can also be further improved when the actuator geometry is modified to fit the specific application. In this paper, three common actuator designs are studied: wires, which are lightweight, low-profile, and easily implemented; springs, which offer actuation strokes upwards of 200% at reduced mechanical loads; and torque tubes, which can provide large actuation forces in small volumes and develop a repeatable zero-load actuation response (known as the two-way shape memory effect). The modeling frameworks, which have been implemented in the design tools, are developed for each of these frequently used SMA actuator types. In order to demonstrate the versatility and flexibility of the presented design tools, as well as validate their modeling framework, several design challenges were completed. These case studies include the design and development of an active hinge for the deployment of a solar array or foldable space structure, an adaptive solar array deployment and positioning system, a passive air temperature controller for the regulation of flow temperatures inside of a jet engine, and a redesign of the Corvette active hatch, which allows for pressure equalization of the car interior. For each of the presented case studies, a prototype or proof-of-concept was fabricated and the experimental results and lessons learned are discussed. This analysis presents a collection of CASMART collaborative best practices in order to allow readers to utilize the available design tools and understand their modeling principles. These design tools, which are based on engineering models, can provide first-order optimal designs and are a basic and efficient method for either demonstrating design feasibility or refining design parameters. Although the design and integration of an SMA-based actuation system always requires application- and environment-specific engineering considerations, common modeling tools can significantly reduce the investment required for actuation system development and provide valuable engineering insight.

The aim of the present study was to examine the protective effects and mechanisms of S100 calcium-binding protein A4 (S100A4) on endothelial cell apoptosis induced by oxidative stress injury. Endothelial cells were cultured and divided into control and oxidative stress injury groups, with the latter state induced by H2O2. Endothelial cells in every group were incubated with or without 50 or 100 µM S100A4. The cell viability and amounts of malondialdehyde, nitric oxide and lactate dehydrogenase in the culture medium were measured. The apoptotic index was detected by TUNEL staining. Western blot and immunoprecipitation analyses were used to detect the expression levels and the association between S100A4 and P53. H2O2 treatment led to oxidative stress injury in the cultured vascular endothelial cells, a decrease in the cell viability and an increase in the rate of apoptosis of vascular endothelial cells compared with the negative control group. Exogenous S100A4 serves a significant function against oxidative stress injury (P

Sleep disorders negatively affect cognition and health. Recent evidence has indicated that chromatin remodeling via histone acetylation regulates cognitive function. This study aimed to investigate the possible roles of histone acetylation in sleep deprivation (SD)-induced cognitive impairment. Results of the Morris water maze test showed that 3 days of SD can cause spatial memory impairment in Wistar rats. SD can also decrease histone acetylation levels, increase histone deacetylase 2 (HDAC2) expression, and decrease histone acetyltransferase (CBP) expression. Furthermore, SD can reduce H3 and H4 acetylation levels in the promoters of the brain-derived neurotrophic factor (Bdnf) gene and thus significantly downregulate BDNF expression and impair the activity of key BDNF signaling pathways (pCaMKII, pErk2, and pCREB). However, treatment with the HDAC inhibitor trichostatin A attenuated all the negative effects induced by SD. Therefore, BDNF and its histone acetylation regulation may play important roles in SD-induced spatial memory impairment, whereas HDAC inhibition possibly confers protection against SD-induced impairment in spatial memory and hippocampal functions.

A new methodology has been developed to compare texture development and macroscopic response predictions of micromechanical shape memory alloy models directly with diffraction data. Using these methods empirical neutron diffraction data from sequential, multi-axial, compressive loading schemes were compared with calculations from the simplified multivariant model. Through this process the ability of a multivariant model to predict both the texture development and mechanical response trends during the creation of complex stress states in martensitic polycrystalline NiTi was demonstrated for the first time. The result made it evident that a multivariant model is more completely validated through simultaneous verification of micro and macroscale predictions as opposed to only verifying macroscale predictions, as was the previous state of the art. The new methodology presented here provides the means to perform this multiscale verification for any multivariant model. It is also shown that in combining a multivariant model with diffraction techniques a new tool for examining the plausibility of variant growth and depletion mechanisms has been created.

The feasibility of using SMA wires to improve the seal effectiveness has been studied experimentally and numerically. In this article, we present only the numerical study of simulating the thermo-mechanical behavior for an SMA enhanced lip seal, leaving the test setup and results in the experimental counterpart. A pseudo 3D SMA model, considering 1D SMA behavior in the major loading direction and elastic response in other directions, was used to capture the thermo-mechanical behavior of SMA wires. The model was then implemented into ABAQUS using the user-defined material subroutine to inherit most features of the commercial finite element package. Two-way shape memory effect was also considered since the SMA material exhibits strong two-way effects. An axisymmetric finite element model was constructed to simulate a seal mounting on a shaft and the sealing pressure was calculated for both the regular seal and the SMA enhanced seal. Finally, the result was qualitatively compared with the experimental observation.

Mechanical responses and texture developments were observed in situ during the creation of multiaxial stress states in polycrystalline NiTi parallelepiped specimens, achieved via sequential compression along unique principal axes. For all of the compression stages, regardless of initial texture, the two major texture components behaved similarly: (1 0 0) poles aligned with, while (0 1 1) poles oriented perpendicular to, the loading direction. The effective critical resolved shear stress needed to induce significant reorientation, however, was reduced through prior loading. In the macroscopic responses, prior transverse direction loading resulted in widening of the reorientation plateau, a reduction of the effective Young’s modulus, and substantial alteration of effective Poisson’s ratios during axial direction straining. Additionally, these empirical results are presented in a manner conducive to the verification of shape memory alloy micromechanics and continuum mechanics constitutive models.

It has been previously reported that the plasma levels of autoantibodies against heat shock protein 70 (HSP70) are elevated in atherosclerosis. The aim of the present study was to elucidate whether anti-HSP70 antibodies are involved in the pathogenesis of atherosclerosis. To determine this, we chose rats as an atherosclerosis model. Titers of plasma anti-HSP70 autoantibody were determined by ELISA. After the intravenous administration of antibody into the tail, the damaged areas of aorta were stained with Evans Blue, atheromatous plaque were stained by Oil Red O, and then they were measured and quantified with AxioVision computer software. The number of macrophages (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {{\hbox{M}}_\Phi } $$\end{document}), smooth muscle cells (SMCs), and T cells were determined by immunocytochemistry. The level of anti-HSP70 IgG1 antibody was apparently increased in the AS group at the tenth week, and one hybridoma of HSP70 antibody (BD091, IgG1, recognizing C-terminal) had the same binding epitope as plasma anti-HSP70 autoantibodies. After intravenous administration, the lesion area of aorta with BD091 was significantly larger than those of IgGmouse and SPA-810. Moreover, injection of BD091 resulted in significant endothelium damage, followed by a greater accumulation of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {{\hbox{M}}_\Phi } $$\end{document}, T cells, and SMCs in lesions than in the control. In conclusion, BD091 reaction with HSP70 expressed on arterial endothelial cells inducing endothelium damage triggers the inflammatory response in the vessel wall that accelerates atherosclerosis in rats. BD091 shares the same binding epitope with HSP70 autoantibodies. These data indicated that a specific epitope of anti-HSP70 autoantibody participated in the pathogenesis of atherosclerosis.

The high degree of cross-reactivity of Envelope (E) protein specific antibody responses between ZIKV and DENV made it difficult to perform differential diagnosis between the two infections using standard ELISA method for E protein. The analyses of the sequential serum samples from ZIKV infected individuals showed NS1 specific Abs appeared two weeks later than E specific Abs. Notably, there is none cross-reactivity to NS1 proteins from all four DENV serotypes in human sera from ZIKV infection. Furthermore, four out of five NS1-specific monoclonal antibodies (mAbs) isolated from ZIKV infected individuals did not bind to DENV NS1 proteins. Only limited cross-binding to ZIKV NS1 was displayed in 108 DENV1 immune sera at 1:100 dilution. The high degree of NS1-specific Abs in both ZIKV and DENV infection revealed here suggest that NS1-based diagnostics would significantly improve the differential diagnosis between DENV and ZIKV.

Stress is a risk factor for many diseases. In this study, we used fluorescence difference gel electrophoresis combined MALDI-TOF/TOF and 1H-NMR to monitor the intracellular processes in rat liver at proteomic and metabonomic levels when a rat was treated with restraint stress for 8 weeks. Dynamic changes in 42 proteins and 32 chemical groups were monitored and identified. These proteins and chemical groups were implicated in glycolysis, the tricarboxylic acid cycle, fatty acid oxidation, and the urea cycle. To verify the DIGE result, three proteins including DJ-1, Blvrb and AdoHycase were validated by Western blot. Furthermore, some metabolites related to diseases such as lactate, fatty acid, glucose and homocysteine, were observed to be increasing during 8 weeks of restraint stress. Our data indicated that subclinical hepatic injury occurs during restraint stress, including inhibition of glycolysis and gluconeogenesis in the liver, and dysfunction of fatty acid beta-oxidation. The results suggest a comprehensive map that addresses how functional proteins act on metabolites to produce energy and process materials in rat liver as it responds to restraint stress. Further functional study on these dynamic change proteins and metabolites may lead to better understanding of the mechanisms of stress-induced diseases.

A physically based one-dimensional shape memory alloy (SMA) model is implemented into the finite element software ABAQUS via a user interface. Linearization of the SMA constitutive law together with complete transformation kinetics is performed and tabulated for implementation. Robust rules for transformation zones of the phase diagram are implemented and a new strategy for overlapping transformation zones is developed. The iteration algorithm, switching point updates and solution strategies are developed and are presented in detail. The code is validated via baseline simulations including the shape memory effect and pseudoelasticity and then further tested with complex loading paths. A hybrid composite with self-healing function is then simulated using the developed code. The example demonstrates the usefulness of the methods for the design and simulation of materials or structures actuated by SMA wires or ribbons.

The second part of this two-part paper summarizes work on the micromechanical modeling of polycrystalline shape memory alloys (SMAs). Averaging micromechanics methods based on the self-consistent approximation are used for the modeling of polycrystalline SMA thermomechanical behavior. The predictions of several models are directly compared and correlated with experimental results. Rate independent phenomenological models are then discussed, which are based on characterizing the inelastic fields associated with the phase transformation and transformation induced plasticity by using internal state variables. The resulting evolution equations are integrated using return mapping algorithms. Selected numerical simulations and comparison of the phenomenological models with the micromechanical ones are also presented.

International audience; This two-part paper reviews the latest developments in the modeling of shape memory alloys (SMAs) constitutive behavior. The basic properties of SMAs are presented in Part I, including the shape memory effect, pseudoelasticity, as well as other properties such as the acquired and two-way shape memory effect, damping capacity and fatigue life. Part I focuses on the modeling at the single crystal level, dealing with the kinematics of the phase transformation and addressing different approaches for the development of the free energy and dissipation in order to derive constitutive equations. Some of the commonly used SMAs are reviewed by chemical composition and thermomechanical properties. The effects that different processing techniques have on their properties are also discussed. The kinematics associated with the martensitic phase transformation in a single crystal is described for a cubic to tetragonal and cubic to monoclinic transformation, and the lattice invariant strain by plastic slip is discussed. The transformation strain in a representative volume element (RVE) and its evolution are then defined. The free energy and dissipative potentials are derived together with the interaction energy for single variant and multivariant formulations in single crystals. A discussion on scale transitions to polycrystalline SMAs is finally presented. Part II deals with the polycrystalline modeling, considering both micromechanical approaches and phenomenological ones. It also includes considerations about the numerical implementation of SMA constitutive models and their integration into finite element codes.

A self-healing, metal matrix composite reinforced by shape memory alloy wires is simulated using finite element analysis. A one-dimensional constitutive model for SMA behavior is implemented as a user-defined truss element in ABAQUS. The matrix is brittle and a mode I crack is allowed to propagate through the specimen upon loading. During the loading process the wires undergo a martensitic phase transformation, bridging the crack. To heal the composite, simple heating is required which reverse transforms the wires and brings the crack faces back into contact. When using pre-strained SMA wires for reinforcement, the reverse transformation of the wires during heating causes a closure force across the crack. The method to simulate cracking and “healing” behaviors of the composite allow assessment of the effects of component properties and composite geometry. The results shed light on design of self-healing composites using shape memory alloys.

Shape memory alloy (SMA) actuators are becoming increasingly popular in recent years due to their properties such as large recovery strain, silent actuation and low weight. Actuation in SMA wires depends strongly on temperature which is difficult to measure directly. Therefore, a reliable model is required to predict wire temperature, in order to control the transformation, and hence the actuation, and to avoid potential degradation due to overheating. The purpose of this investigation is to develop resistance and natural convection heat transfer models to predict temperature of current-carrying SMA wires using indirect temperature measurement methods. Experiments are performed on electrically heated 0.5 mm diameter NiTi SMA wire during phase transformation. Convection heat transfer experiments are performed in an environment of air that allows for control of the ambient pressure and in turn the thermofluid properties, such as density and viscosity. By measuring convective heat loss at a range of pressures, an empirical natural convection heat transfer correlation is determined for inclination angles from horizontal to vertical, in the Rayleigh number range of 2.6 × 10−8 ≤ RaD ≤ 6.0 × 10−1. Later, effect of temperature changes on electrical resistance and other control parameters such as applied external stress, wire inclination angle, wire length and ambient pressure is investigated. Based on experimental results a resistance model is developed for SMA wires that combined with the heat transfer correlation previously derived can be used to predict temperature and natural convection heat transfer coefficient of NiTi SMA wires during phase transformation for different wire lengths and inclination angles under various applied external stresses.

The Multivariant model describing shape memory alloy (SMA) constitutive behavior is further developed in this paper for improved prediction of thermomechanical response. In the original formulation of the Multivariant model, an interaction energy, representative of the incompatibility of an inclusion to the matrix, was calculated by a micromechanics model in which every variant group (inclusion) was embedded in the austenite phase with numerous other inclusions. However, experiments show that martensite variants tend to form large plates most of which have an invariant plane interface with the austenite and reach the grain boundary. Hence, to better simulate material behavior, in the revised model the micromechanical interaction energy is replaced by a small, constant term. The predictions by the new model for different uniaxial tension directions on a single CuAlNi crystal have excellent agreement with the experimental results. Furthermore, the counterintuitive results for a polycrystal CuZnAl under triaxial loading are also well captured by the new model. As the revised model removes an iterative procedure for interaction energy, calculations are simplified, making the Multivariant model more suitable for larger scale computations.

The newly emerged Zika virus (ZIKV) belonging to the flavivirus family, may appear in the area dengue virus (DENV) infection occurred, raising the issue of diagnosis. The secreted NS1 protein from infected cell is not only an important diagnostic marker but also highly immunogenic. Here we investigated the cross-reaction of NS1 Ab responses between the two close related viruses. First we studied the binding of sera to the recombinant full length NS1 from three ZIKV infected patients (Samples collected at day 4, 7, 15, 106, 188 and 321 for patient 1; day 6, 12, and 66 for patient 2; day 2 for patient 3) by capture ELISA. ZIKV NS1 binding IgG markedly increased in convalescent sera from patient 1 and patient 2 with less cross-reaction to DENV 1–4 NS1. The serum from patient 3 did not bind to ZIKV NS1 and that may be explained by the early time point of serum collected on day 2 from the symptom onset. Specificity of ZIKV NS1 Ab response was evidenced by lack of reactivity to DENV 1–4 NS1proteins of memory B cell derived mAbs (4/5) isolated from the two ZIKV-infected. Only one mAb (1/5) cross-reacted to DENV 2 and DENV 4 NS1. Strikingly NS1 Ab responses of DENV1 infected (six samples) which serotype frequently circulates in our area, Guangdong, China with outbreak in 2014 showed strong cross-reactivity between DENV serotypes with mild or strong reaction to ZIKV NS1. Our data indicated that NS1 Ab response elicited by Zika virus infection was ZIKV-specific and the ZIKV specific mAb can be used for diagnostic tool.

Organ fibrosis has been viewed as a major medical problem that leads to progressive dysfunction of the organ and eventually the death of patients. Stress-related hormone norepinephrine (NE) has been reported to exert fibrogenic actions in the injured organ. Nix plays a critical role in pressure overload-induced cardiac remodeling and heart failure through mediating cardiomyocyte apoptosis. However, cardiac remodeling also includes fibrosis. Whether Nix is involved in stress-induced fibrosis remains unclear. The present study was designed to determine the role of Nix in NE-induced NIH/3T3 fibroblasts. The results showed that Nix was upregulated and closely associated with cell proliferation, collagen and fibronectin expression in NIH/3T3 fibroblasts following NE treatment. Overexpression of Nix promoted collagen and fibronectin expression, whereas the suppression of Nix resulted in a strong reduction in collagen and fibronectin expression. Moreover, the increases in collagen and fibronectin expression induced by NE were successively increased when Nix was overexpressed and reduced when Nix was inhibited. Furthermore, we demonstrated that the PKC activation is responsible for the upregulation of Nix induced by NE. Inhibition of Nix expression with α-adrenoceptor antagonist, β-adrenoceptor antagonist or PKC inhibitor attenuated NE-induced collagen and fibronectin expression. Our data revealed that Nix is a novel mediator of NE-induced fibrosis. Thus, it would provide a new insight into the development of effective preventative measures and therapies of tissue fibrosis.