Structure Evolution and Properties Modification for Reaction-Bonded Silicon Carbide.

Complex structure reaction-bonded silicon carbide (RB-SiC) can be prepared by reactive melt infiltration (RMI) and digital light processing (DLP). However, the strength and modulus of RB-SiC prepared by DLP are not sufficient, due to its low solid content (around 40 vol.%), compared with the traditional fabrication techniques (solid content > 60 vol.%). With this understanding, a new method to improve the properties of RB-SiC was proposed, by the impregnation of composite precursor into the porous preform. The composite precursor was composed of phenolic (PF) resin and furfuryl alcohol (FA). PF and FA were pyrolyzed at 1850 °C to obtain amorphous carbon and graphite into the porous preform, respectively. The effects of multiphase carbon on the microstructure and performance of RB-SiC was studied. When the mass ratio of PF to FA was 1/4, the solid content of RB-SiC increased from 40 vol.% to 68.6 vol.%. The strength, bulk density and modulus were 323.12 MPa, 2.94 g/cm3 and 348.83 Gpa, respectively. This method demonstrated that the reaction process between liquid Si and carbon could be controlled by the introduction of multiphase carbon into the porous preforms, which has the potential to regulate the microstructure and properties of RB-SiC prepared by additive manufacturing or other forming methods.

BRD4 expression in patients with essential hypertension and its effect on blood pressure in spontaneously hypertensive rats.

The objective of this study was to investigate BRD4 expression in patients with essential hypertension (EH) and its effects on the blood pressure in spontaneously hypertensive (SHR) rats. BRD4 expression was detected by quantitative real-time polymerase chain reaction and western blot in 163 patients with EH and its relation to systolic blood pressure and diastolic blood pressure were analyzed accordingly. In vivo, rats were divided into WKY (Wistar-Kyoto rats), SHR (spontaneously hypertensive rats), SHR + JQ1 (BRD4 inhibitor), and SHR + Vehicle control. Rats' blood pressure was measured by the tail-cuff method. The protein expressions related to inflammation and oxidative stress of rats were determined. BRD4 was higher in patients with EH than healthy controls, which was positively correlated to systolic blood pressure and diastolic blood pressure of enrolled subjects including patients with EH and healthy controls. Rats in the SHR group showed reduced food-intake, decreased body weight, and gradually increased blood pressure compared with WKY group. Besides, SHR rats were upregulated in plasma levels of Ang II, ET-1, MDA, IL-6, and TNF-α, and substantially downregulated in NO, NOS, and SOD levels. Moreover, eNOS activity in aortic tissues of SHR rats declined obviously, whereas the content of nitrite and O2-, the activity of NADPH oxidase and NADH oxidase, and the expression of p-NF-κB p65 went up statistically, which could be partially reversed by JQ1. BRD4 was highly expressed in patients with EH, and inhibiting BRD4 could reduce oxidative stress and inflammatory response, alleviate endothelial cell damage, ameliorate aortic injury, and lower blood pressure, supporting the hypothesis that BRD4 inhibition could be a potential target for the clinical treatment of patients with EH.

[Effect of nano-SiO2 exposure on spatial learning and memory and LTP of hippocampal dentate gyrus in rats].

OBJECTIVE: To study the effect of nano-SiO2 on spatial learning and memory. METHODS: Twenty-four male rats were randomly divided into 3 groups: control group (C group), low dose group (L group) and high dose group (H group). The rats were intragastrically administrated with nanometer particles at 25 and 100 mg/kg body weight every day for 4 weeks. After exposure, the ability of learning and memory of rats was tested by Morris water maze, and electrophysiological brain stereotactic method was used to test long-tear potentiation (LTP) in dentate gyrus (DG) of the rats. RESULTS: The increase rate of body weight in H group was reduced significantly compared with C group ( P < 0.05). In the space exploration experiment of Morris water maze test, the escape latency of H group was longer than that of C group (P < 0.05). The rats of H group spent less time in finding the target quadrant (P < 0.05) . The rate of LP induction of H group was significantly lower than that of C group (P < 0.05). After high fre quency stimulation (HFS), The changes of amplitude of population spike (PS) of L group and H group were lower than those of C group significantly (P < 0.05, P < 0.01). CONCLUSION: Nano-SiO2may result in impairment of spatial learning and memory ability by reducing the rate of LTP induction and the increase of PS in hippocampus.

Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer's Disease-Like Amyloid-ß Pathology and Neuroinflammation in the Rat Hippocampus.

A putative etiological association exists between noise exposure and Alzheimer's disease (AD). Amyloid-ß (Aß) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aß may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays, and RT-PCR, to examine both hippocampal Aß pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aß, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, ß- and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor-AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aß and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD.

Functional expression, characterization and application of the human S100A4 protein.

Preparations utilizing monoclonal antibodies against S100A4 provide useful tools for functional studies to investigate the clinical applications of the human S100A4 protein. In the present study, human S100A4 protein was expressed in Escherichia coli (E. coli) BL21 (DE3), successfully purified by diethylaminoethyl cellulose anion-exchange chromatography and identified by western blot analysis. Soluble S100A4 bioactivity was confirmed by Transwell migration and invasion assays in the human HeLa cell line. Monoclonal antibodies (mAbs) were generated utilizing the standard hybridoma method and were validated by enzyme-linked immunosorbent assay and western blot analysis. The antibody was then used to examine human gastric carcinoma specimens by immunohistochemistry. Recombinant S100A4 was functionally expressed in E. coli and promoted the migration and invasion of HeLa cells. Four hybridoma cell lines, which secreted mAbs specifically against human S100A4 protein, were obtained. One of the four mAbs, namely 2A12D10B2, recognized human S100A4 as indicated by immunohistochemical staining of human gastric carcinoma specimens and recombinant S100A4 was functionally expressed in E. coli. The mAbs of recombinant S100A4 were suitable for detecting S100A4 expression in human tissues and for investigating the subsequent clinical applications of the protein.

Functionally active rat S100A4 from a polymerase chain reaction-synthesized gene expressed in soluble form in Escherichia coli.

S100A4 protein is associated with Ca2+-dependent regulation of intracellular activities and is significant in the invasion, growth and metastasis of cancer. In order to express rat S100A4 functionally and identify its biological activity following purification, an S100A4 gene fragment was optimized and fully synthesized via overlapping polymerase chain reaction. The gene was inserted into the prokaryotic expression vector, pBV220, with phage λ PRPL promoters following confirmation by DNA sequencing. The pBV220-S100A4 plasmid was constructed and transformed into Escherichia coli DH5α. Following temperature induction, rat S100A4 was overexpressed and the protein was observed to be located in the supernatant of the lysates, which was ~30-40% of the total protein within the host. The protein was isolated and purified by metal-chelate affinity chromatography. High purity protein (>98% purity) was obtained and in vitro western blot analysis identified that the recombinant S100A4 was able to bind to the antibody against wild-type S100A4. The bioactivity of the recombinant protein was detected via Transwell migration and invasion assays. The polyclonal antibody of rat S100A4 protein was prepared for rabbit immunization and exhibited similar efficacies when compared with commercial S100A4. Therefore, rat S100A4 was functionally expressed in E. coli; thus, the production of active recombinant S100A4 protein in E. coli may further aid with the investigation and application of S100A4.

Role of NMDA receptors in noise-induced tau hyperphosphorylation in rat hippocampus and prefrontal cortex.

Chronic noise exposure has been associated with abnormalities in glutamate (Glu)-NMDAR signaling and tau hyperphosphorylation. However, further studies are necessary to clarify potential causal relationships. The aim of the present study was to evaluate the role of NMDA receptors in noise-induced tau hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar rats were randomly divided into three groups in the present study: control with isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d × 14d) and treated with saline (n=10); and noise exposure and treated with MK-801 (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202 and Ser396, and proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3ß (GSK3ß) and protein phosphatase 2A (PP2A), were measured in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We showed that phosphorylated tau levels were enhanced in noise-exposed-rat hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202 and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise-induced GSK3ß overexpression but had no significant effect on PP2A levels. This suggests that MK-801 protects against chronic-noise-induced tau hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that Glu-NMDAR signaling may be involved in triggering aberrant tau hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.

[Effects of retinol acid and triiodothyronine on alleviating the impairment of cognitive function by sleep deprivation].

OBJECTIVE: To explore the effects of retinol acid (RA) and triiodothyronine (T3) on alleviating the impairment of cognitive function by sleep deprivation (SD). METHODS: Male Wistar rats were divided into 4 groups: control group (C group), sleep deprivation group (SD group), sleep deprivation + RA group (SD + RA group) and sleep deprivation + T3 group (SD + T3 group). Open field test (OFT) was used to observe the nervous behavior of the rats after SD and electrophysiological brain stereotactic method was used to test long-term potentiation (LTP) in dentate gyrus (DG) of the rats. Ng protein expression was determined by Western blot. RESULTS: Compared with the SD group, the number of crossing in OFT, the changes of amplitude of population spike (PS) and the expression of Ng protein in hippocampus were higher significantly in the SD + RA and SD + T3 groups. All of these had not significant difference comparing with the C group. CONCLUSION: RA and T3 may alleviate the restrain state of neural system after SD by augmenting the expression of Ng protein in hippocampus.

Overexpression of S100A4 is closely associated with the progression and prognosis of gastric cancer in young patients.

The aim of this study was to determine the correlation of S100A4 expression with the progression, prognosis and clinical pathology of gastric cancer (GC) in young pateints. A total of 85 tumor tissues with corresponding adjacent normal tissues and 62 non-metastatic lymph nodes (LNs) with corresponding metastatic LNs were obtained from young GC patients (<40 years old) who underwent surgery between January 2001 and December 2006. The expression of S100A4 was detected by RT-PCR and immunohistochemistry. Differences in the expression of S100A4 mRNA or protein were observed among the GC tissues, matched normal gastric mucosa, non-metastatic LNs and metastatic LNs. The expression of S100A4 mRNA and protein in GC tissues and metastatic LNs was significantly higher compared with that in the matched normal gastric mucosa and non-metastatic LNs, respectively (P<0.05). The overexpression of S100A4 was significantly associated with parameters involved in tumor progression and poor prognosis, including tumor size (P=0.017), Lauren classification (P=0.002), histological classification (P= 0.010), histological differentiation (P= 0.000), Borrmann classification (P=0.020), tumor-node-metastasis (TNM) stage (P=0.000), LN metastasis (P=0.000) and distant metastasis (P=0.024). Multivariate analysis suggested that patient age (P=0.035), tumor size (P=0.002), TNM stage (P=0.001) and S100A4 upregulation (P=0.000) were independent prognostic indicators for the disease. The overexpression of S100A4 in young GC patients is significantly associated with the clinicopathological characteristics. S100A4 may be used as a biomarker to predict the progression and poor prognosis of GC in young patients.

Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex.

The non-auditory effects of noise exposure on the central nervous system have been established both epidemiologically and experimentally. Chronic noise exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes. However, experimental evidence for these associations remains limited. The aim of the current study was to explore the effects of CNE [100 dB sound pressure level (SPL) white noise, 4 h/d×14 d] on tau phosphorylation in the rat hippocampus and the prefrontal cortex. Forty-eight male Wistar rats were randomly assigned to two groups: a noise-exposed group and a control group. The levels of radioimmunoprecipitation assay (RIPA)-soluble and RIPA-insoluble phosphorylated tau at Ser202, Ser396, Ser404, and Ser422 in the hippocampus and the prefrontal cortex were measured at different time points (days 0, 3, 7, and 14) after the end of the last noise exposure. Exposure to white noise for 14 consecutive days significantly increased the levels of tau phosphorylation at Ser202, Ser396, Ser404, and Ser422, the sites typically phosphorylated in AD brains, in the hippocampus and the prefrontal cortex. Tau hyperphosphorylation persisted for 7 to 14 d after the cessation of noise exposure. These alterations were also concomitant with the generation of pathological neurofibrillary tangle (NFT) tau 3, 7 and 14 d after the end of the stimulus. Furthermore, lasting increases in proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3ß (GSK3ß) and protein phosphatase 2A (PP2A), were found to occur in close correspondence with increase in tau hyperphosphorylation. The results of this study show that CNE leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our results also provide evidence for the involvement of GSK3ß and PP2A in these processes.

Versatile synthesis of α-substituted taurines from nitroolefins.

A series of 1-substituted and 1,1-disubstituted taurines were synthesized from nitroolefins via the Michael addition with sodium ethylxanthate, oxidation with performic acid, and reduction with hydrogen in the presence of palladium on carbon powder. The current route is a versatile and salt-free method for synthesis of both aliphatic and aromatic 1-substituted and 1,1-disubstituted taurines.

Changes of 5-hydroxytryptamine and tryptophan hydroxylase expression in the ventral horn of spinal cord.

OBJECTIVE: To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryptophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mechanism of exercise-induced central fatigue at spinal level. METHODS: Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analyzed quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. RESULTS: Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P< 0.05). CONCLUSION: 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue.

[The changes of neurotransmitter content in spinal cord after exercise-induced central fatigue].

AIM: To investigate the changes of neurotransmitter concentration in spinal cord after exercise-induced central fatigue and study the mechanism of central fatigue at spinal level. METHODS: Establish exercise-induced central fatigue model according to Bedford incremental loading training. The rats were divided into three groups, control group (C), immediately after training group (IT), rest 3 hours after training group (RT). Then using high performance liquid chromatography (HPLC) to detect the concentration of neurotransmitter in spinal cord. RESULTS: Amino acid neurotransmitters in spinal cord increased in IT group: Glu, GABA increased significantly (P < 0.05), Gly also increased but have no statistic difference; while in RT group, amino acid neurotransmitters got back to normal. However monoamine neurotransmitters NE, 5-HT tended to decrease in IT group. In RT group 5-HT decreased dramatically (P < 0.05). CONCLUSION: Exercise-induced fatigue changed the concentration of neurotransmitter in spinal cord.The results suggested that neurotransmitter in spinal cord might have relationship with exercise-induced fatigue, especially 5-HT might have more important effect on recovery of fatigue.