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In the complex mountain wind environment, especially in the strong wind, fluctuating wind speed is a non-stationary and non-Gaussian random process. With the increase of suspension bridges’ span, they are more sensitive to wind-induced vibration response. In this paper, a non-stationary and non-Gaussian buffeting reliability analysis method for long-span bridges is presented. Firstly, the non-stationary wind speed is simulated by the modulation function based on the stationary wind speed model. Secondly, the load is obtained by simulated wind speed, the obtained loads are loaded on the finite element model by ANSYS and the whole bridge time-domain analysis is performed, the time history of displacement response is obtained. Thirdly, based on the first excursion failure criterion of random vibration, the samples of the non-stationary and non-Gaussian displacement time history are transformed into a standard Gaussian process through a modified Fleishman approximation method, and then the non-stationary Poisson distribution method is used for structural reliability analysis. Finally, a mountainous long-span suspension bridge is used as the engineering background, and the proposed reliability analysis method is applied to analyze the reliability of the bridge. The influence of different wind attack angles and modulation functions on the dynamic reliability of the bridge is further studied. The results indicate that the displacement response obtained by the transformation of non-stationary and non-Gaussian random process is less reliable than that obtained by traditional analysis method. Its dynamic reliability is maximum at 1[Formula: see text] wind attack angle, the reliability of negative wind attack angle is lower than that of positive wind attack angle, and decreases with the increase of wind attack angle. The reliability obtained by using different modulation functions is lower than that of traditional method. If the traditional analysis method is still used for reliability analysis, it will produce unsafe consequences and reduce the engineering safety reserve.

Fungal infections cause ~1.5 million deaths each year worldwide, and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria. The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species. Therefore, a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies. Here, we report that DOCK2 (dedicator of cytokinesis 2) promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages. DOCK2-deficient macrophages exhibit decreased RAC GTPase (Rac family small GTPase) activation and ROS (reactive oxygen species) production, which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways. Mechanistically, after fungal stimulation, activated SYK (spleen-associated tyrosine kinase) phosphorylates DOCK2 at tyrosine 985 and 1405, which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation. Importantly, nanoparticle-mediated delivery of in vitro transcribed (IVT) Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo. Taken together, this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.

Biomass burning is an important source of polycyclic aromatic hydrocarbons (PAHs) and elemental carbon (EC), but the formation mechanisms are still unclear. Cellulose, hemicellulose, and lignin are the three major components of biomass. In this study, the three-components extracted from three typical biomass raw materials were used for laboratory combustion experiments, to investigate the differences in the emission factors and chemical compositions of PAHs and EC. The average emission factors of the 16 kinds of PAHs were showing as lignin (135 ± 180 mg/kg)cellulose (97.8 ± 124 mg/kg)hemicellulose (48.9 ± 65.2 mg/kg), and the average emission factors of EC presented in the descending order of cellulose (1.65 ± 3.02 g/kg), lignin (1.30 ± 1.04 g/kg), and hemicellulose (0.450 ± 0.480 g/kg), respectively. The proportion of naphthalene emitted from cellulose and hemicellulose combustion is higher, while fluoranthene and pyrene accounted significantly higher proportion for lignin. Moreover, the influence of ignition temperature and oxygen content on the emission characteristics of PAHs and EC were also discussed. The influence of ignition temperature on the emission of EC and PAHs is more significant compared to oxygen content, because it obviously promoted the PAHs and EC formations through resonance-stabilized hydrocarbon-radical chain reaction (RSR) pathway. However, correlation analysis combined with cluster analysis showed that the RSR-pathway probably had different effects on PAH growth for the three-components, as the indene-involved RSR-pathway were mainly related to 4-6 ring PAHs for cellulose and lignin (except fluoranthene and pyrene), but 2-4 ring PAHs for hemicellulose. We also found that the fitted results according to the proportion of three-components were significantly higher than the measured values of raw materials for indene, medium-molecular-weight PAHs, and soot-EC. These results presented the different formation pathways for medium-molecular-weight PAHs and the two EC components emitted by biomass combustion, which are worthy of further studies in exploring the generation mechanisms of PAHs and EC.

Shopee has been a popular online shopping website in the Southeast Asia. Customers appreciate its easy, secure, and fast online shopping experience tailored to their region. At the same time, it allows customers to choose the one with the lower price of the same product. It relies on the product matching, that is the same product with the same description image must be removed. The base technology to achieve this function is multimodal learning, in which we focus on the images and text. In our article, we proposed a new multimodal learning model mainly based on transformer and BERT. For image matching, we use NFNet, Swin_Transformer and Efficientnet to get image embeddings. For text matching, we use Distil-Bert, Albert, Multilingual Bert and TF-IDF to get text embeddings. After we get the embedding vector, we choose KNN to classify. We use cosine and distance to measure the similarity of the different models. It is worth mentioning that the loss function is Arcface, not the traditional Softmax, which improve the difficulty of training to ensure the final performance in the test periods. In addition, 7 models vote for the final results ensuring the effect of prediction. To avoid the bad matching result, we add some postprocessing process.

Significance Each year, the global mortality rates for fungal diseases now exceed those for malaria and breast cancer and are currently comparable to those for tuberculosis and HIV. The limited scope of currently available antifungal drugs is the major factor underlying the observed high mortality rate. Here, we provide evidence that Myosin IF (MYO1F) plays a critical role in the mediating of signaling molecules “trafficking from membrane to cytoplasm,” and this process is essential for the antifungal signaling pathway activation. Moreover, we provide evidence that Sirt2 deacetylase inhibitors promote antifungal immunity and protect mice from lethal Candida albicans infection, which indicates that the Sirt2 could be a good therapeutic target for the antifungal drug development., Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9. Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans. Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow–derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

Background Primary familial brain calcification (PFBC) is a rare inheritable neurodegenerative disease characterized by bilateral calcification in different brain regions and by a range of neuropsychiatric symptoms. Six causative genes of PFBC (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified. Methods Sanger sequencing was used to identify the causative genes associated with PFBC in this study. Results We describe the first PFBC case with both SLC20A2 and PDGFRB heterozygous mutations. Notably, this patient with the digenic mutation (who was only 5 years old) showed severe brain calcification and migraine, whereas the patient's parents, who each carried a heterozygous mutation in SLC20A2 or PDGFRB, exhibited varying degrees of brain calcification but were clinically asymptomatic. Conclusion This case highlights the digenic influences on the characteristics of PFBC patients., We report a family in which the members have various genetic states and manifestations of PFBC. Notably, the proband carrying the SLC20A2 and PDGFRB heterozygous mutations showed more severe brain calcification and earlier onset age of clinical symptoms than her family members, highlighting digenic influences on the characteristics of PFBC patients.

All electric aircraft demand for new electrical drive train topologies. Following the application of a previously presented cryogenic cooled permanent magnet synchronous machine, this paper investigates a new concept of hydrogen cooling. Giving a brief overview of the initial machine design, a direct end winding cooling will be shown, exploiting the beneficial behaviour of thermal conductivity at low temperatures. As an additional step, an auxiliary closed-loop helium cooling will be presented. Besides the outline of the cooling concept, the design procedure will be presented from scratch, starting with analytical approximations culminating in FEA. In the end a final design solution will be discussed, showing that the initial requirements can be reached with the proposed design concept.

The tissue factor pathway inhibitor (TFPI) gene encodes a protease inhibitor with a critical role in regulation of blood coagulation. Some genomic variants in TFPI were previously associated with plasma TFPI levels, however, it remains to be further determined whether TFPI variants are associated with other coagulation factors. In this study, we carried out a large population-based study with 2,313 study subjects for blood coagulation data, including fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). We identified significant association of TFPI variant rs10931292 (a functional promoter variant with reduced transactivation) with increased plasma fibrinogen levels (P=0.017 under a recessive model), but not with PT, APTT or TT (P>0.05). Using a large case control association study population with 4,479 CAD patients and 3,628 controls, we identified significant association between rs10931292 and CAD under a recessive model (OR = 1.23, P = 0.005). For the first time, we show that a TFPI variant is found to be significantly associated with fibrinogen levels and risk of CAD. Our finding contributes significantly to the elucidation of the genetic basis and biological pathways responsible for fibrinogen levels and development of CAD.

LaFeO3 is a promising visible light photocatalyst due to its favorable band gap and excellent stability in aqueous solution. The cathodic photocurrent for p-type characteristics reversing to anodic photocurrent on a LaFeO3 photoanode is observed under visible light (>420 nm) and the anodic photoelectrochemical water oxidation performance is improved by electro-deposition of amorphous cobalt-phosphate (Co-Pi). It shows that the presence of Co-Pi down-shifts the onset potential by ∼560 mV for anodic photocurrent, and the improvement can be attributed to enhanced water oxidation due to the CoII/CoIII-OH discharge in Co-Pi decorated layers by cyclic voltammetry test. The transition anodic photocurrent is improved by about six times after Co-Pi coating under visible light at 0.50 V vs. Ag/AgCl and the electrochemical impedance spectroscopy certifies the enhanced charge transfer, which contributes to the meliorative anodic photocurrent. The suppression of the photogenerated electron–hole recombination after Co-Pi coating on LaFeO3 photoanode is directly demonstrated by the reduced photoluminescence spectrum. Combined with the accelerated carrier consumption on the surface and enhanced carrier separation on the photoanode, the incident photon-to-current conversion efficiencies of LaFeO3 can be promoted from 1.37% to 2.14% at 400 nm owing to the presence of the Co-Pi layer.

Background— Genomic variants identified by genome-wide association studies (GWAS) explain Methods and Results— Mining of GWAS data was performed to analyze variants in 32 complement system genes for positive association with CAD. Functional variants in genes showing positive association were then identified by searching existing expression quantitative loci databases and validated by real-time reverse transcription polymerase chain reaction. A follow-up case–control design was then used to determine whether the functional variants are associated with CAD in 2 independent GeneID Chinese populations. Candidate pathway-based GWAS identified positive association between variants in C3AR1 and C6 and CAD. Two functional variants, rs7842 in C3AR1 and rs4400166 in C6 , were found to be associated with expression levels of C3AR1 and C6 , respectively. Significant association was identified between rs7842 and CAD ( P =3.99×10 −6 ; odds ratio, 1.47) and between rs4400166 and CAD ( P =9.30×10 −3 ; odds ratio, 1.24) in the validation cohort. The significant findings were confirmed in the replication cohort ( P =1.53×10 −5 ; odds ratio, 1.37 for rs7842; P =8.41×10 −3 ; odds ratio, 1.21 for rs4400166). Conclusions— Integration of GWAS with biological pathways and expression quantitative loci is effective in identifying new risk variants for CAD. Functional variants increasing C3AR1 and C6 expression were shown to confer significant risk of CAD for the first time.

Background The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabetic patients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes. Materials and Methods We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls. Results rs3134069 showed significant association with ischemic stroke in the China-Central population (P = 9.24 × 10−3, odds ratio [OR] = 1.50). The association was replicated in the independent China-Northern population (P = 2.45 × 10−4, OR = 1.53). The association became more significant in the combined population (P = 7.09 × 10−6, OR = 1.41). The associations remained significant in the male population, female population, and population without type 2 diabetes. Our expression quantitative trait loci analysis found that the minor allele C of rs3134069 was significantly associated with a decreasedexpression level of TNFRSF11B (P = .002). Conclusions This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.

BACKGROUND: The anthocyanins of Kyoho grape juice-making pomace, Cabernet Sauvignon grape winemaking pomace and their fresh skin were identified and quantified by high-performance liquid chromatography‐tandem mass spectrometry, and the influence of processing on the anthocyanin profiles was investigated. RESULTS: Twenty-three and 16 anthocyanins were found in fresh skin of Kyoho and Cabernet Sauvignon grapes, respectively. Malvidin 3-(trans)-coumaroyl-5-diglucoside and malvidin 3-glucoside were the most abundant anthocyanin in fresh skin of Kyoho and Cabernet Sauvignon grapes, respectively. The cis and trans isomers of malvidin 3-coumaroyl-5-diglucoside are reported in Kyoho grape for the first time. In addition, the anthocyanin content of juice-making pomace of Kyoho grapes and winemaking pomace of Cabernet Sauvignon grapes was significantly lower than the fresh skin samples (p < 0.05). The percentage variation of non-acylated anthocyanins was lower than that of acylated anthocyanins in all pomace samples. CONCLUSION: Kyoho grape and Cabernet Sauvignon grape showed distinctive anthocyanin profiles. Juice-making pomace is a better source of anthocyanins for use in functional foods than winemaking pomace. c � 2012 Society of Chemical Industry

The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE(-/-) background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD.We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1249 CAD cases and 841 controls in Population I, 1260 cases and 833 controls in Population II and 790 cases and 1212 controls in Population III (a total of 3299 cases and 2886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj = 2.18 × 10(-5), OR = 1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj = 5.43 × 10(-5), OR = 1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2.The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression of CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans.

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.

Accumulation of the hyperphosphorylated tau is a hallmark pathological event for the formation of neurofibrillary tangles in Alzheimer disease (AD). Until now, there is no effective way to antagonize this accumulation. Recently, it has been reported that carboxyl terminus of Hsc70-interacting protein (CHIP) is the specific tau E3 ligase and it mediates tau degradation in vitro. However, the nature of CHIP on in vivo tau degradation is not fully understood. Here, we demonstrated that hippocampal transfection of CHIP plasmid in rats could reach a time-dependent elevated expression of CHIP mRNA and protein in 24 h. Concomitantly, expression of exogenous CHIP could promote the degradation of the hyperphosphorylated tau induced by overactivation of glycogen synthase kinase-3 (GSK-3) or inhibition of protein phosphatase-2A (PP-2A) in the rat brains and N2A cells. CHIP also degraded tau in normal rats regardless the phosphorylation status of tau proteins. Though CHIP overexpression was not able to improve significantly the spatial memory retention deficits induced by overactivation of GSK-3, it did not cause significant damage to the memory function in normal rats. These results suggest that CHIP may degrade tau both in physiological and pathological conditions without affecting the behavior of the rats, implying that overexpression of CHIP may antagonize tau accumulation in the AD brains.

Formation of neurofibrillary tangle from hyperphosphorylated tau is one of the hallmark lesions seen in Alzheimer's disease (AD) brain, and neuronal deregulation of glycogen synthase kinase-3 (GSK-3) activity plays key role in tau hyperphosphorylation. In the present study, the role of GSK-3 on tau phosphorylation in hippocampus slice culture was examined by incubating the slice with wortmannin (WT), an inhibitor of phosphatidylinositol 3-kinase (PI3K) and GF-109203X (GFX), an inhibitor of protein kinase C (PKC). It was found that treatment of the slices with GFX or WT separately induced tau hyperphosphorylation both at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1) sites. The phosphorylation rate of tau at PHF-1 and Tau-1 epitopes was further increased when GFX and WT were used in combination, and at this condition, AD-like tau accumulation was observed. GSK-3 activity was significantly increased with a concurrently decreased level of inactivated form of GSK-3. Lithium chloride (LiCl), a GSK-3 inhibitor, prevented tau from WT- and GFX-induced hyperphosphorylation. It suggests that GSK-3 is regulated through PI3K and PKC pathway, and activation of GSK-3 not only induces hyperphosphorylation of tau but also leads to accumulation of tau in cultured rat brain slice.

Abnormal hyperphosphorylation of tau and cholinergic deficit occur in the early stage of Alzheimer's disease (AD) and relate to the dementia symptom. Hyperphosphorylation of tau, neurofilament (NF) and other proteins in AD brain appears to be caused by a down-regulation of protein phosphatase 2A (PP2A), but the mechanism leading to cholinergic deficit is still unknown. In this study, we selectively inhibited PP2A by injection of okadaic acid (OA) into the Meynert nucleus basalis of rats. We found that injection of OA induced hyperphosphorylation of tau and NF and decreased acetylcholine (ACh) level in the nucleus basalis of Meynert. These alterations were accompanied by spatial memory deficit in OA-injected rats. We also demonstrated that the OA-induced ACh reduction may be due to a failure of intraneuronal transport of choline acetyltransferase (ChAT) from cell body to the neuronal terminals rather than an alteration of activity of ChAT or acetylcholinesterase. This study suggests that a down-regulation of PP2A may underlie both abnormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration and cholinergic deficiency in AD.

As the expanding of city and the increasing of roads and vehicles, the traffic system become more and more complex and difficult to be managed. In order to make better use of existing transport resources to achieve optimal traffic scheduling, a lot of countries have launched Intelligent Transport Systems, the system is able to obtain a massive amount of traffic information, but it is a worthy study problem that how to make efficient use of vast amounts of information to give the driver the information which is real-time, accurate. The vehicle has characteristics such as mobile, large number, needing personalized information, as well as intelligent transport platform's information blows up which is caused by huge amounts of data, so that personal intelligent transportation applications rarely appear. This paper using Tablet PC equipped with android platform as personal terminal, it's easier to connect to the ubiquitous network using android platform's various methods of wireless access such as GPRS, 3G, WIFI and so on. After location-based intelligent search searching in the traffic information platform, drivers can know the latest real-time traffic information of the surrounding. Using the method of this paper can make efficient use of mass transportation information, and ultimately achieve “safe travel”.

During purification of porcine gut polypeptides with respect to glucose-induced insulin secretion from pancreatic β cells, two novel fragments of the known gastrointestinal peptides were isolated and chemically characterized. They are truncated forms of phosphatidylethanolamine-binding protein (PEBP93-124) and valosin (Valosin3-25). These novel fragments, Valosin3-25 and PEBP93-124, showed stimulatory activities on glucose-induced insulin secretion from pancreatic β cells. That the novel fragments had their respective bioactivities imply that these novel peptide-fragments could be the novel processed peptide-forms in organism. Therefore, isolation and chemical characterization of bioactive peptides from natural materials in the post genomic and bio-informational era are still necessary and will help scientist to have deeper insight into proteomics. In addition, these purified porcine gut polypeptides may provide an option to the treatment of Diabetes and also bring limelight to the mechanism of Diabetes manifestation. Keywords: Insulin, truncated peptide, phosphatidylethanolanmine binding protein, valosin, glucose-dependent insulinotropic polypeptide.

Chronic obstructive pulmonary disease (COPD) is considered a complex genetic disorder and it is expected that many genes play a role in the pathogenesis of this disease. Previous studies have reported that several variations within the interleukin (IL)-18 gene promoter region have been associated with different inflammatory diseases such as asthma. However, the association of IL-18 promoter polymorphisms with COPD has not been studied yet. We then performed a prospective case-control study to explore this association in male smokers of Chinese Han people. Our study recruited 112 COPD cases and 105 healthy controls matched for age. The genotyping of IL-18 promoter polymorphisms (-607 C/A and -137 G/C) was performed using TaqMan single nucleotide polymorphism genotyping assays. The frequencies of the alleles and genotypes in patients and controls were compared. We found that the frequency of IL-18 -607 C allele was significantly increased in patients with COPD (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.01-2.15, P = 0.04). The frequency of IL-18 -607 C allele was significantly higher in the GOLD (Global initiative for Obstructive Lung Disease) 3-4 group compared with the GOLD 1-2 group (OR=2.06, 95% CI = 1.21-3.51, P = 0.01). There were no significant differences in the frequencies of the alleles and genotypes of IL-18 -137 G/C polymorphism between the patients and healthy smokers or between GOLD 3-4 group and GOLD 1-2 group. Our study revealed that the IL-18 -607 C/A polymorphism was associated with COPD susceptibility and severity of airflow limitation in male smokers of Chinese Han people.

The quantification of acrylamide in foods was investigated by gas chromatography-mass spectrometry (GC-MS). In this method, (13)C3-acrylamide was used as an internal standard. The samples were homogenized, defatted with hexane and extracted with ethyl acetate for twice. The derivatization of acrylamide into 2-bromopropenamide (2-BPA) was done using potassium bromide/potassium bromate at 4 degrees C for 90 min. Selective ion monitoring mode was chosen to monitor objective chromatography. This method had a good linearity between 0.05-2.00 mg/kg (r2 = 0.9995), and the limits of detection and quantification were 3 microg/kg and 7 microg/kg, respectively. The recoveries of acrylamide were in the range of 62.7%-65.5%. In order to confirm this GC-MS method, the acrylamide in foods was also determined by high performance liquid chromatography coupled to quadrupole tandem mass spectrometry (HPLC-MS/MS), which had been proved in our laboratory. The concentrations of acrylamide in the samples quantified by GC-MS were slightly higher than those detected by HPLC-MS/MS. This method can be used to quantify acrylamide in normal foods.

Electroconvulsive therapy has been commonly applied in the treatment of refractory depression, but its cognitive side effects are noticed and restrict its application. The molecular mechanisms underlying the side effects remain elusive, and there is no efficient prevention. By employing a recognized electroconvulsive shock (ECS) rat model, we found in the present study that ECS induced spatial memory deficits with simultaneous decreases in synaptic proteins of N-methyl-D-aspartate receptor 2A/B (NR2A/B) and postsynaptic density 95 (PSD95), the immediate early gene c-Fos and cAMP response element binding (CREB) proteins, all of which are memory-related proteins. ECS also caused tau hyperphosphorylation at multiple Alzheimer-related phosphorylation sites with activation of glycogen synthase kinase-3beta (GSK-3beta), Akt and phospho-PKR-like endoreticulum (PERK), and inhibition of protein phosphatase-2A (PP)-2A. Intraperitoneal injection of phenylbutyric acid (PBA), an aromatic short chain fatty acid with the functions of molecule chaperon, prevented rats from the ECS-induced memory deficits, alterations of the memory-associated proteins, and tau hyperphosphorylation. Our data suggest that PBA may be potentially used for attenuating the side effects caused by electroconvulsive therapy.

It has been suggested that hyperpolarization-activated cyclic-nucleotide-gated cation non-selective channel (HCN) 1 is primarily expressed in the hippocampus and can be regulated in many pathological settings. However, little is known about its change under ischemic conditions. In the present study, we performed neurophysiological recordings of sham-operated and chronic ischemic rats with hypoperfusion during the resolution of the neurological deficits respectively. In situ hybridization methods and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were used to investigate whether and how HCN1 mRNA may be altered in global incomplete chronic cerebral ischemic rat model. Our results suggested that attenuated spatial learning and memory function of rats shown by longer escape latency, shorter time spent in the target quadrant and impaired long-term potentiation (LTP) after chronic cerebral ischemia. In the in situ hybridization cytochemistry experiment, HCN1 mRNA declined to 52.00% and 46.00% of the control values in the cornus ammon 1 (CA1) regions of hippocampus and neocortex separately after chronic cerebral ischemia. HCN1 mRNA in the hippocampal CA1 region and neocortex was markedly down regulated by ischemia, reaching 48.90% and 45.80% of the control values respectively in the semi-quantitative RT-PCR experiment. The phenomenon opened new insights for further investigation of the physiological and pathological significances of HCN1 in chronic incomplete global cerebral ischemia.

Although neurofibrillary tangles and senile plaques have been identified as the hallmark pathological changes in the brain of Alzheimer's disease (AD), the relationship between them is still not fully understood. In the present study, we have studied the effect of endogenously overproduced amyloid beta (A beta) on tau by using wild type amyloid precursor protein (APP) transfected (N2a/APP695), or Swedish mutant APP plus Delta 9 deleted presenilin-1 co-transfected (N2a/APPswe.Delta 9) and APP vector transfected (N2a/vector) cell lines. We measured the secreted and intracellular A beta, including A beta(1-40) and A beta(1-42), by Sandwich ELISA assay. It was shown that the levels of A beta were increased time-dependently in N2a/APP695 and N2a/APPswe.Delta 9 but not in N2a/vector upon butyric acid (BA) treatment. Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment. Obvious accumulation of the hyperphosphorylated tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was observed at 48 h after BA treatment. The total level of the extracted tau was reduced in N2a/APP695 and N2a/APPswe.Delta 9 lines compared with N2a/vector cells by Western blot, and this reduction of total tau was also detected by immunofluorescence staining. No obvious alteration of tau mRNA was observed in both N2a/APP695 and N2a/APPswe.Delta 9 cells compared with N2a/vector. This study provides direct evidence demonstrating that endogenously overproduced A beta not only induces tau hyperphosphorylation but also decreases the level and solubility of tau in N2a cell lines.