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Matrix metalloproteinases (MMPs) and the epithelial-mesenchymal transition (EMT) contribute to metastasis. As shown in our previous studies, interleukin-6 (IL-6) induces ATM phosphorylation to increase MMP expression and metastasis in lung cancer. However, the exact roles of ATM activation in the IL-6-induced epithelial-mesenchymal transition and lung cancer metastasis are currently unclear. Here, ATM phosphorylation exerts its pro-metastatic effect via vimentin-mediated epithelial-mesenchymal transition, which was supported by the evidence described below. Firstly, IL-6 treatment increases vimentin expression via the ATM-NF-κB pathway. Second, ATM inactivation not only abolishes IL-6-induced increases in vimentin expression but also inhibits IL-6-induced nest formation in a xenograft lung metastasis model. Moreover, close positive correlations were observed between ATM phosphorylation and vimentin upregulation, IL-6 levels and metastasis in lung cancer specimens. Hence, ATM modulates vimentin expression to facilitate IL-6-induced epithelial-mesenchymal transition and metastasis in lung cancer, indicating that ATM and vimentin might be potential therapeutic targets for inflammation-associated lung cancer metastasis.

Abnormal angiogenesis and regression of the diseased retinal vasculature are key processes associated with ischemic retinopathies, but the underlying mechanisms that regulate vascular remodeling remain poorly understood. Here, we confirmed the specific expression of semaphorin 3G (Sema3G) in retinal endothelial cells (ECs), which was required for vascular remodeling and the amelioration of ischemic retinopathy. We found that Sema3G was elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and in the neovascularization regression phase of oxygen-induced retinopathy (OIR). Endothelial-specific Sema3G knockout mice exhibited decreased vessel density and excessive matrix deposition in the retinal vasculature. Moreover, loss of Sema3G aggravated pathological angiogenesis in mice with OIR. Mechanistically, we demonstrated that HIF-2α directly regulated Sema3G transcription in ECs under hypoxia. Sema3G coordinated the functional interaction between β-catenin and VE-cadherin by increasing β-catenin stability in the endothelium through the neuropilin-2 (Nrp2)/PlexinD1 receptor. Furthermore, Sema3G supplementation enhanced healthy vascular network formation and promoted diseased vasculature regression during blood vessel remodeling. Overall, we deciphered the endothelium-derived Sema3G-dependent events involved in modulating physiological vascular remodeling and regression of pathological blood vessels for reparative vascular regeneration. Our findings shed light on the protective effect of Sema3G in ischemic retinopathies.

Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase &alpha, /&beta, (IKK&alpha, ) activation, the exact roles of Akt phosphorylation, IKK&alpha, or IKK&beta, activation in endotoxin-containing pathogen-derived cross-presentation are poorly understood. In this study, endotoxin-free ovalbumin supplemented with endotoxin was used as a model pathogen. We investigated the effects of endotoxin-containing pathogen and endotoxin-free antigen on Akt phosphorylation, IKK&alpha, activation, and explored the mechanisms that the endotoxin-containing pathogen orchestrating the endosomal recruitment of Sec61 of the cross-presentation in bone marrow precursor cells (BMPC). We demonstrated that endotoxin-containing pathogen and endotoxin-free antigen efficiently induced the phosphorylation of Akt-IKK&alpha, and Akt-IKK&alpha, respectively. Endotoxin-containing pathogen derived Akt+ IKK&alpha, + Rab5+ signalosome, together with augmented the recruitment of Sec61 toward endosome, lead to the increased cross-presentation in BMPC. Importantly, the endosomal recruitment of Sec61 was partly mediated by the formation of Akt+ IKK&alpha, + signalosome. Thus, these data suggest that Akt+ IKK&alpha, + Rab5+ signalosome contribute to endotoxin-containing pathogen-induced the endosomal recruitment of Sec61 and the superior efficacy of cross-presentation in BMPC.

Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer’s disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons. Gab1 overexpression, on the other hand, improved cognitive function and restored hippocampal CaMKII autorphosphorylation in AD mice. These results suggest that Gab1 plays an important role in the pathophysiology of AD and may represent a novel therapeutic target for diseases involving cholinergic dysfunction.

Morin, is a natural bioflavonoid isolated from Chinese herbs of the Moraceae family, has been reported to possess antidiabetic activity. However, the role of morin on glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation in diabetic condition is still unclear. Therefore, in this study, we investigated the role of morin on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. Our results showed that morin inhibited HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21Waf1/Cip1 and p27Kip1. It also inhibited HG-induced ECM expression, ROS generation and NOX4 expression in MCs. Furthermore, morin suppressed HG-induced phosphorylation of p38 MAPK and JNK1/2 in MCs. These data suggest that morin inhibits HG-induced MC proliferation and ECM expression through suppressing the activation of p38 MAPK and JNK signaling pathways. Thus, morin may be useful for the prevention or treatment of diabetic nephropathy.

Cross-presentation by dendritic cell (DC) requires the endosomal relocations of internalized exogenous antigens and endoplasmic reticulum protein Sec61. In despite that the treatment with antigens activates Akt and NF-κB pathways, the exact roles of Akt phosphorylation and NF-κB activation in cross-presentation are still poorly understood. In this study, we investigate the roles of Akt phosphorylation, IKKα/β activation and the mechanism that the antigens orchestrating the recruitment of Sec61 toward endosomes in cross-presentation. We demonstrate that the treatment with exogenous antigens increases the formation of Akt+IKKα/β+ signalosome on Rab5+ endosomes and augments the endosomal recruitment of Sec61 in the process of DC cross-presentation. Interestingly, TRIF/MyD88-dependent the formation of Akt+IKKα/β+ signalosomes mediates the relocation of Sec61 toward endosomes. Importantly, the MyD88-IRAK4 signaling contributes to exogenous ovalbumin-derived cross-presentation by recruiting Akt+IKKα/β+ signalosomes toward endosomes. Thus, these data suggest that TRIF/MyD88-dependent the formation of Akt+IKKα/β+ signalosome on Rab5+ endosomes contributes to the endosomal recruitment of Sec61 and the superior cross-presentation efficacy of antigen activated DC.

Highlights • Serum neutralizing antibodies to Ad5 and Ad41 in adults and children were titrated. • Prevalence of NAb in children was associated with age and sanitary conditions. • NAb titer distribution pattern was very different between Ad5 an Ad41. • Ad41 vectored vaccine candidates might have a bright future., Neutralizing antibody (NAb) can dampen the immunogenicity of adenovirus (Ad) vector-based vaccine. Vector systems based on human adenovirus type 41 (Ad41) have been constructed and used to develop recombinant vaccines. Here, we attempted to study the seroprevalence of NAbs to Ad5 and Ad41 among children and adults in Qinghai province, China. The positive rates (titer ⩾ 40) of Ad5 and Ad41 NAb in adults from Xining city were 75.7% and 94.7%, respectively. The moderate/high-positive rates (titer ⩾ 160) of NAb were quite close between the two viruses in adults (70.4% for Ad5 and 73.5% for Ad41). Age-dependent increase of NAb seroprevalence was observed for both viruses in children. NAb-positive rate of Ad41 reached 50% at 3.3–4.6 years of age for children from Chengxi district, Xining city, approximately 1.5 years earlier than that of Ad5 did. Interestingly, NAb level was also associated with sanitary conditions among young children. For Ad5, 8–15% children (0.2–3.0 years of age) from city or town, where the sanitations were relatively better, had moderate/high-positive NAb, while the same rate was 62% for children from villages. For Ad41, 22% children from city, 47% from town and 88% from villages possessed moderate/high-positive NAb. The possible influence of NAb titer distributions on the application of Ad41-vectored vaccines was discussed in detail. Our results suggested that children from places with poor sanitations should be included for comprehensive Ad NAb seroprevalence studies, and provided insights to the applications of Ad41 vectors.

Clinical treatment for vascular dementia still remains a challenge mainly due to the blood-brain barrier (BBB). Here, a micelle based on polysialic acid (PSA), which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was first chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behavior over a period of 72 h with a 3.6% (w/w) drug content and a 107.0 ± 4.0 nm size was then fabricated. The PSA-ODA micelle could cross the BBB mainly via active endocytosis by brain endothelial cells followed by transcytosis. In a water maze test for spatial learning, calmodulin antagonist loaded PSA-ODA micelle significantly reduced the escape latencies of right unilateral common carotid arteries occlusion (rUCCAO) mice with dosage significantly reduced versus free drug. The decrease of hippocampal phospho-CaMKII (Thr286/287) and phospho-synapsin I (Ser603) was partially restored in rUCCAO mice following calmodulin antagonist loaded PSA-ODA micelle treatment. Consistent with the restored CaMKII phosphorylation, the elevation of BrdU/NeuN double-positive cells in the same context was also observed. Overall, the PSA-ODA micelle developed from the endogenous material might promote the development of therapeutic approaches for improving the efficacy of brain-targeted drug delivery and have great potential for vascular dementia treatment.

Liu et al. reveal a key mechanism that mediating the transition from cerebrovascular damage to epilepsy. They identify the endothelial cyclin-dependent kinase 5 (CDK5) regulates astrocytic glutamate reuptake and increased glutamate synaptic function through CXCL1/CXCR2-mediated astrogliosis., Blood–brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy., Graphical Abstract

This communication reports on a fluorescent probe (PPI-P) for imaging active peptidyl-prolyl cis/trans isomerases in live cells. PPI-P is capable of responding to both recombinant and cellular PPIases fluorogenically, and has been shown to specifically image active PPIases in live cells.

The pathogenic mechanism of ALS remains unclear. However, increasing evidence has indicated that uric acid (UA) may play a protective role in the pathogenesis of ALS. The aim of this study was to evaluate the association between serum UA levels and ALS. A comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library was conducted up to 31st August, 2017, using keywords. A random-effects model or fixed-effects model was used to calculate the pooled estimate according to the inter-group heterogeneity. Finally, we indentified 8 case-control and 3 cohort studies. The results indicated that patients with ALS had significant decreased levels of serum UA compared to healthy controls (standardized mean difference (SMD) = −0.72, 95% CI [−0.98,−0.46], P

Accumulating evidence suggests that formation of peroxynitrite (ONOO(-)) in the cerebral vasculature contributes to the progression of ischemic damage, while the underlying molecular mechanisms remain elusive. To fully understand ONOO(-) biology, efficient tools that can realize the real-time tracing of endogenous ONOO(-) fluxes are indispensable. While a few ONOO(-) fluorescent probes have been reported, direct visualization of ONOO(-) fluxes in the cerebral vasculature of live mice remains a challenge. Herein, we present a fluorescent switch-on probe (NP3) for ONOO(-) imaging. NP3 exhibits good specificity, fast response, and high sensitivity toward ONOO(-) both in vitro and in vivo. Moreover, NP3 is two-photon excitable and readily blood-brain barrier penetrable. These desired photophysical and pharmacokinetic properties endow NP3 with the capability to monitor brain vascular ONOO(-) generation after injury with excellent temporal and spatial resolution. As a proof of concept, NP3 has enabled the direct visualization of neurovascular ONOO(-) formation in ischemia progression in live mouse brain by use of two-photon laser scanning microscopy. Due to these favorable properties, NP3 holds great promise for visualizing endogenous peroxynitrite fluxes in a variety of pathophysiological progressions in vitro and in vivo.

Septic encephalopathy (SE) is a critical factor determining sepsis mortality. Vascular inflammation is known to be involved in SE, but the molecular events that lead to the development of encephalopathy remain unclear. Using time-lapse in vivo two-photon laser scanning microscopy, we provide the first direct evidence that cecal ligation and puncture in septic mice induces microglial trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral microvessels. Our data further demonstrate that septic injury increased the chemokine CXCL1 level in brain endothelial cells by activating endothelial P2RX7 and eventually enhanced the binding of Mac-1 (CD11b/CD18)-expressing leukocytes to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis-induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1 expression and leukocyte adhesion but also prevented microglia overactivation, reduced brain injury, and consequently doubled the early survival of septic mice. These results demonstrate the role of the P2RX7 pathway in linking neurovascular inflammation to brain damage in vivo and provide a rationale for targeting endothelial P2RX7 for neurovascular protection during SE.

Cholinergic anti-inflammatory pathway has therapeutic effect on inflammation-associated diseases. However, the exact mechanism of nicotine-mediated anti-inflammatory effect is still unclear. TIPE2, a new member of tumor necrosis factor-α-induced protein-8 family, is a negative regulator of immune homeostasis. However, the roles of TIPE2 in cholinergic anti-inflammatory effect are still uncertain. Here, we demonstrated that nicotine exerts its anti-inflammatory effect by TIPE2 upregulation and phosphorylated stat3 mediated the inhibition of NF-κB activation, which was supported by the following evidence: firstly, both nicotine and TIPE2 inhibit pro-inflammatory cytokine release via NF-κB inactivation. Secondly, nicotine upregulates TIPE2 expression via α7 nicotinic acetylcholine receptor. Moreover, the enhancement of stat3 phosphorylation and decrease of LPS-induced p65 translocation were achieved by nicotine treatment. Importantly, nicotine treatment augments the interaction of phosphorylated stat3 and p65, indicating that the inhibitory effect of nicotine on NF-κB activation was mediated with protein-protein interactions. Hence, this study revealed that TIPE2 upregulation and stat3 phosphorylation contribute to nicotine-mediated anti-inflammation effect, indicating that TIPE2 and stat3 might be potential molecules for dealing with inflammation-associated diseases.

Severe hypoglycemia has a detrimental impact on the cerebrovasculature, but the molecular events that lead to the disruption of the integrity of the tight junctions remain unclear. Here, we report that the microvessel integrity was dramatically compromised (59.41% of wild‐type mice) in TP53‐induced glycolysis and apoptosis regulator (TIGAR) transgenic mice stressed by hypoglycemia. Melatonin, a potent antioxidant, protects against hypoglycemic stress‐induced brain endothelial tight junction injury in the dosage of 400 nmol/L in vitro. FRET (fluorescence resonance energy transfer) imaging data of endothelial cells stressed by low glucose revealed that TIGAR couples with calmodulin to promote TIGAR tyrosine nitration. A tyrosine 92 mutation interferes with the TIGAR‐dependent NADPH generation (55.60% decreased) and abolishes its protective effect on tight junctions in human brain microvascular endothelial cells. We further demonstrate that the low‐glucose‐induced disruption of occludin and Caludin5 as well as activation of autophagy was abrogated by melatonin‐mediated blockade of nitrosative stress in vitro. Collectively, we provide information on the detailed molecular mechanisms for the protective actions of melatonin on brain endothelial tight junctions and suggest that this indole has translational potential for severe hypoglycemia‐induced neurovascular damage.

Dysfunction of neurovascular pericytes underlies breakdown of the blood-brain barrier, but the molecular mechanisms are largely unknown. In this study, we evaluated the role of the transient receptor potential melastatin-related 2 (TRPM2) channel and autophagy during brain pericyte injury both in vitro and in vivo.A rapid induction in autophagy in human brain vascular pericytes, in the zinc oxide nanoparticles (ZnO-NP)-induced cell stress model, was paralleled with an increase in the expression of the TRPM2-S truncated isoform, which was abolished by treatment with a nitric oxide synthase inhibitor and a peroxynitrite scavenger. Furthermore, Y1485 in the C-terminus of the TRPM2 protein was identified as the tyrosine nitration substrate by mass spectrometry. Overexpression of the Y1485S TRPM2 mutant reduced LC3-II accumulation and pericyte injury induced by ZnO-NP. Consistently, LC3-II accumulation was reduced and pericytes were better preserved in intact brain microvessels of the TRPM2 knockout mice after ZnO-NP-induced vascular injury. Innovation and Conclusions: Our present study has revealed a novel mechanism of autophagy disturbance secondary to nitrosative stress-induced tyrosine nitration of TRPM2 during pericyte injury. Antioxid. Redox Signal. 27, 1297-1316.

SummaryAims The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Results Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Conclusions Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders.

The present study was designed to investigate the role of autophagy-lysosome signaling in the brain after application of nanoparticles. Here, lipid nanoparticles (LNs) induced elevations of Atg5, P62, LC3 and cathepsin B in mice brain. The transmission electron microscopy revealed a dramatic elevation of lysosome vacuoles colocalized with LNs cluster inside the neurons in mice brain. Immunoblot data revealed abnormal expression of cathepsin B in brain cortex following LNs injection, whereas its expression was further elevated in Atg5 +/− mice. The importance of Atg5 in the LNs-induced autophagy-lysosome cascade was further supported by our finding that neurovascular response was exaggerated in Atg5 +/− mice. In addition, the siRNA knockdown of Atg5 significantly blunted the increasing of LC3 and P62 in LNs-treated Neuro-2a cells. Taken together, we propose that LNs induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway. From the Clinical Editor These authors investigated autophagy-lysosome signaling in the mouse brain after application of lipid nanoparticles and report that these nanoparticles induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway.

Aims: Although there is accumulating evidence that increased formation of reactive nitrogen species in cerebral vasculature contributes to the progression of ischemic damage, but the underlying molecular mechanisms remain elusive. Peroxiredoxin 1 (Prx1) can initiate the antioxidant response by scavenging free radicals. Therefore, we tested the hypothesis that Prx1 regulates the susceptibility to nitrosative stress damage during cerebral ischemia in vitro and in vivo. Results: Proteomic analysis in endothelial cells revealed that Prx1 was upregulated after stress-related oxygen–glucose deprivation (OGD). Although peroxynitrite upregulated Prx1 rapidly, this was followed by its polyubiquitination within 6 h after OGD mediated by the E3 ubiquitin ligase E6-associated protein (E6AP). OGD colocalized E6AP with nitrotyrosine in endothelial cells. To assess translational relevance in vivo, mice were studied after middle cerebral artery occlusion (MCAO). This was accompanied by Prx1 ubiquitination and degradation by the activation of E6AP. Furthermore, brain delivery of a lentiviral vector encoding Prx1 in mice inhibited blood–brain barrier leakage and neuronal damage significantly following MCAO. Innovation and Conclusions: Nitrosative stress during ischemic insult activates E6AP E3 ubiquitin ligase that ubiquitinates Prx1 and subsequently worsens cerebral damage. Thus, targeting the Prx1 antioxidant defense pathway may represent a novel treatment strategy for neurovascular protection in stroke. Antioxid. Redox Signal. 21, 1–16.

The proper interactions between blood vessels and neurons are critical for maintaining the strength of neural circuits and cognitive function. However, the precise molecular events underlying these interactions remain largely unknown. Here, we report that the selective knockout of semaphorin 3G (Sema3G) in endothelial cells impaired hippocampal-dependent memory and reduced dendritic spine density in CA1 neurons in mice; these effects were reversed after restoration of Sema3G levels in the hippocampus by AAV transfection. We further show that Sema3G increased excitatory synapse density via neuropilin-2/PlexinA4 signaling and through activation of Rac1. These results provide the first evidence that, in the central nervous system, endothelial Sema3G serves as a vascular-derived synaptic organizer that regulates synaptic plasticity and hippocampal-dependent memory. Our findings highlight the role of vascular endothelial cells in regulating cognitive function through intercellular communication with neurons in the hippocampus.

Database encryption is the last defense to ensure data security, resolving the problem of insecurity caused by unencrypted data directly stored in database. At the same time, Database encryption has brought a new troubleencryption makes query efficiency become obviously slow. Cryptograph index is an effective method. In the DAS(Database as a service) model, a method based on bucket partitioning and B+ tree, which utilizes B+ tree to sort data in the bucket and improves the efficiency due to reduce the amount of processing data, is put forth in this paper. Finally, the paper has made an analysis on its performance.

This study aims to perform a survey of genetic variation in neuraminidase (NA) gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors, in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino acid sequences was performed by MEGA 4.0. Phylogenetic trees were also constructed. Strains isolated during 2010-2011 in this study clustered closely with World Health Organization (WHO) 2010-2012 reference vaccine strain A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the phylogenetic tree, while the 2012 isolates were located on another branch. In analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the 2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K, P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a glycosylation site to the activity center of NA. No significant variation was discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of 2012 were found with significant mutation, which has the potential of inducing minor resistance to NA inhibitors like zanamivir and oseltamivir.

Chlorine and chlorine dioxide are widely used for water disinfection nowadays. To establish standard technical process for total chlorine and chlorine dioxide determination, the factors affected total chlorine and chlorine dioxide determination by DPA method were researched in this paper. Temperature should be balanced at 20℃ in determination and pH value should be controlled between 5 and 9. The reaction time should be controlled within 5 minutes for the best results. The interference of metal ions can be eliminated by adding glycine or potassium iodide solution in determination of chlorine dioxide. The results using this method showed no significant difference with using the method GB/T 5749-2006. The research provides support on establishing the standard technical process for rapid determination of total chlorine and chlorine dioxide in drinking water.

An investigation was conducted to identify the distribution of mosquitoes and mosquito-borne arboviruses in the Qinghai-Tibet Plateau, China from July to August in 2007. A total of 8,147 mosquitoes representing six species from three genera (Aedes, Culex, and Anopheles) were collected in three locations (Geermu city, altitude of 2,780 m; Xining city, 2,200 m; Minhe county, 1,700 m). Six virus isolates were obtained including Tahyna virus (TAHV), Liaoning virus, and Culex pipiens pallens Densovirus. A serosurvey showed immunoglobulin G antibodies by immunofluorescence assay (IFA) against TAHV in residents of all three locations. The IFA-positive human samples were confirmed by 90% plaque-reduction neutralization tests (PRNT(90)) against TAHV with titers ranging from 1:20 to 1:10,240. In addition, TAHV seropositive cows, sheep, and swine were found in these locations. This investigation represents the first isolation of TAHV from Ae. (Och.) detritus and the first evidence of TAHV infection in residents and livestock in the Qinghai-Tibet Plateau.

The query time was shortened efficiently by adopting sampling method for storing historical stream data. However, important information was discarded in a large possibility because all data were treated non-discriminately with same sampling probability. In this paper, we addressed the problem by introducing a method for storing historical stream data based on degree of interest. The method used parameter Q to indicate the importance of each data, based on which a sampling algorithm had better effect on maintaining the important information. The experimental results showed that the degree of interest based method had fine performance in the query accuracy, especially for simple query on the historical stream data.

In this paper, we propose a Neural Network and cluster based method K-ANN-FP to summarize the frequent itemsets to solve the interpretability obstacle of the large number of frequent itemsets. This method assume that the item exit in each frequent itemsets or not to contribute a Boolean matrix, then take the matrix and the corresponding frequency vectors to train the net. We use cluster to shorten the training time and keep the total restoration in a small threshold. We take the experiment on two UCI datasets; the result shows that the proposed method has fine effect both on the restoration error and the running time.