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A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids.

Purpose: To investigate the effect of chlorobenzoxime on respiratory syncytial virus (RSV) infection in vitro in lung alveolar cells and in vivo in neonatal rats, as well as the mechanism of action involved. Methods: RSV infection in neonatal rats was induced via intranasal administration of 2 x 106PFU viral particles. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used for determination of changes in interleukin expression. Results: RSV infection in BEAS-2B cells caused significant reduction in viability and marked alteration in morphological appearance (p < 0.05). Exposure of RSV-infected BEAS-2B cells to chlorobenzoxime prevented viability reduction and changes in morphology, and led to reductions in RSV-mediated increases in levels of interleukin-6 and interleukin-8. Moreover, RSV infection significantly enhanced ROS levels in BEAS-2B cells, when compared to control cells (p < 0.05). Chlorobenzoxime at a concentration of 30 μM completely suppressed RSV-mediated generation of ROS in BEAS-2B cells. In neonatal rats, RSV-induced upregulation of interleukin-4, interleukin-13 and TNF-α, were suppressed in bronchoalveolar lavage fluid (BALF) and lung tissues by chlorobenzoxime. Moreover, the RSVmediated reduction in IFN-γ was maximally blocked by chlorobenzoxime at a dose of 10 mg/mL. Chlorobenzoxime enhanced the proportion of IFN-γ -producing cells in neonatal rat BALF. Conclusion: Chlorobenzoxime exhibits antiviral against RSV infection in neonatal rats via increase in dendritic cell population, leading to inhibition of cytokine production. Therefore, chlorobenzoxime is a potential therapeutic agent for RSV infection. Keywords: Respiratory syncytial virus, Cytokines, Dendritic cells, Lung aveolar cells, Morphology, Interleukins

Abstracts: Cold-induced RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) have recently been reported to be involved in cold stress in mammals. These proteins are expressed at low levels in various normal cells, tissues, and organs but can be upregulated upon stimulation by multiple stressors. Studies have shown that CIRP and RBM3 are multifunctional RNA molecular chaperones with different biological functions in various physiological and pathophysiological processes, such as reproductive development, the inflammatory response, the immune response, nerve injury regulation, and tumorigenesis. This paper reviews recent studies on the structure, localization and correlation of CIRP and RBM3 with reproductive development and reproductive system diseases.

Acute lung injury (ALI) is a life-threatening disorder related to serious pulmonary inflammation. Narciclasine exhibits strong anti-inflammation activity and attenuates the reactive oxygen species (ROS) production. The present study aims to investigate the underlying mechanism related to the effect of narciclasine on the pathogenesis of neonatal acute lung injury (ALI). Narciclasine attenuated LPS-induced pathological injury and pulmonary edema. In addition, narciclasine suppressed the secretion of inflammatory cytokines, including necrosis factor-α (TNF-α), Interleukin (IL-6), IL-1β, monocyte chemotactic protein-1 (MCP-1) in serum, and inhibited the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of neonatal ALI rats. Furthermore, narciclasine alleviated oxidative stress and apoptosis in lung tissues. Importantly, narciclasine exerted an inhibition effect on NF-κB nuclear translocation and activation of Toll-like Receptor 4 (TLR4)/Nuclear factor (NF)-κB/Cyclooxygenase 2 (Cox2) signaling pathway. Taken together, narciclasine protected against lung injury via inhibition effect on excessive inflammation, oxidative stress and apoptosis, hence, narciclasine may be considered as an effective and novel agent for clinical therapeutic strategy of ALI Treatment., Graphical abstract

Biological nano sensing technology is a new high-tech which is a cross fusion of biology, chemistry, physics, electronics and many other fields. Biological nano sensing technology mainly uses the unique chemical properties and corresponding physical properties of biomolecules at nanometer level to detect, which greatly improves the sensitivity and flexibility of detection. The micro effect, quantum effect and corresponding macro quantum tunneling effect of nano molecules make their corresponding nano biosensors have extremely high detection performance. In this paper, the antiinflammatory drugs such as budesonide, which are used to treat children’s asthma, will be measured by the biological nano sensor based on the new nano materials. The treatment of children after the inhalation of budesonide and other drugs will be measured by the biological nano sensor technology. Finally, a new research idea will be provided for the research of children’s asthma pathology and related fields. In this paper, in the actual preparation of nano sensors, we mainly use functionalized carbon nanotubes to prepare sensors. The main advantage is that the price is low and easy to market and experiment promotion.

Objective Recently, potential correlations between tumor necrosis factor-α (TNF-α) polymorphisms and asthma were investigated by some pilot studies, but the results of these studies were inconsistent. Therefore, we performed this meta-analysis to better evaluate the relationship between TNF-α polymorphisms and the risk of asthma. Methods Eligible studies were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess correlations between TNF-α polymorphisms and asthma. Results A total of 50 studies were included for analyses. Significant associations with the risk of asthma were detected for TNF-α − 238 G/A, −308 G/A and − 857C/T polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that TNF-α − 238 G/A polymorphism was significantly correlated with the risk of asthma in Caucasians, TNF-α − 308 G/A polymorphism was significantly correlated with the risk of asthma in West Asians, TNF-α − 857C/T polymorphism was significantly correlated with the risk of asthma in Caucasians, TNF-α − 863C/A polymorphism was significantly correlated with the risk of asthma in East Asians, and TNF-α − 1031 T/C polymorphism was significantly correlated with the risk of asthma in Caucasians and East Asians. Conclusions Our findings indicated that TNF-α − 238 G/A, −308 G/A, −857C/T, −863C/A and − 1031 T/C polymorphisms may serve as potential biological markers for asthma in certain ethnicities.

Inflammation is a basal host defense response that eliminates the causes and consequences of infection and tissue injury. Macrophages are the primary immune cells involved in the inflammatory response. When activated by LPS, macrophages release various pro-inflammatory cytokines, chemokines, inflammatory mediators, and MMPs. However, unbridled inflammation causes further damage to tissues. Safinamide is a selective and reversible monoamine oxidase B (MAOB) inhibitor that has been used for the treatment of Parkinson's disease. In this study, we aimed to investigate whether safinamide has effects on LPS-treated macrophages. Our results show that safinamide inhibited the expression of pro-inflammatory cytokines such as IL-1α, TNF-α, and IL-6. Furthermore, safinamide suppressed the production of CXCL1 and CCL2, thereby preventing leukocyte migration. In addition, safinamide reduced iNOS-derived NO, COX-2-derived PGE2, MMP-2, and MMP-9. Importantly, the functions of safinamide mentioned above were found to be dependent on its inhibitory effect on the TLR4/NF-κB signaling pathway. Our data indicates that safinamide may exert a protective effect against inflammatory response.

Sero‐epidemiological studies of human papillomavirus (HPV) have been undertaken over the last two decades. In this study, the prevalences of nine serum antibodies (anti‐E6, E7 and L1 antibodies of HPV types 16, 18, and 58) were evaluated in normal (control) Korean women and women with cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and cervical cancer. The frequencies of all types of anti‐HPV antibodies were higher in the CIN stages and cervical cancer than in normal women, and those of anti‐HPV16 E6 and E7, anti‐HPV18 E6 and E7, and anti‐HPV58 E7 antibodies were higher in the cervical cancer group than in the CIN stages. The frequencies of antibodies against HPV16, 18, and 58 E7 tended to increase with increasing severity of cervical lesions. However, there were few differences in the frequencies of antibodies against the L1 antigens of HPV16, 18 and 58 in cervical cancer versus CIN stages. The anti‐HPV antibodies were detected in 26.5% of normal, 46.3% of CIN I, 62.5% of CIN II, 51.6% of CIN III, and 75% of cancers when any of the nine antigens was used as a criterion. Correlations between HPV DNA positivity and seropositivity for anti‐HPV E6, E7, or L1 antibodies were found only in HPV16 DNA‐positive cervical cancers for anti‐HPV16 E6 and L1 antibodies. In addition, strong positive correlations in seropositivity were found between anti‐HPV16 E7 and anti‐HPV58 E7 antibodies, and between anti‐HPV18 E6 and anti‐HPV58 E6 antibodies. These findings should advance global profiling of the seroprevalences of antibodies against HPV antigens.

There has been no attempt to apply protein-based markers of exfoliated cervical cells (ECCs) for primary screening of cervical cancer. In the present study, the levels of six tumor-associated protein [TAPs: Sialyl Lewis A (SLeA), Cancer Antigen 15-3 (CA 15-3), p53, heat shock protein (Hsp)70, Hsp27 and squamous cervical carcinoma antigen (SCCA)]and of two human papillomavirus (HPV) viral proteins (HPV16 E7 and HPV16 L1) of ECCs lysates were evaluated by enzyme-linked immunosorbent assays (ELISAs).The wells of 96-well plates were coated with the ECCs lysates from normal, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cancer groups, and candidate proteins were detected by relevant antibodies. SLeA level decreased with increasing severity of lesions, whereas the levels of other candidate proteins increased. SLeA, HPV16 L1 and p53 levels appeared more useful for detecting cervical lesions than the other candidates. The combination of ELISA-SLeA and ELISA-HPV16 L1 could efficiently detect cervical lesions from normal. The combination of ELISA-SLeA and ELISA-p53 could powerfully discriminate cancer from normal with 91.3% sensitivity and 96.7% specificity. The protein levels of ECCs have great potential as biomarkers for primary screening of cervical cancer.

Elevated serum CA15-3 assessed by enzyme-linked immunosorbent assay (ELISA) has been considered a diagnostic marker of breast cancer. However, accumulating data indicate that the current ELISA system for detecting CA15-3, which targets the peptide backbone of CA15-3, is not sufficiently sensitive to detect early or localized breast cancer. In the present study, we designed an antibody-lectin sandwich assay detecting glycosylation of CA15-3 in patients with breast cancer. Immobilized anti-CA15-3 monoclonal antibody captures CA15-3 in serum, and glycosylation of the CA15-3 is detected with Concanavalin A (ConA) lectin, which preferentially bind high-mannose N-glycans. ConA provided the best signal for detecting serum CA15-3 among 9 types of lectin, Since CA15-3 is a heavily glycosylated protein, detecting the glycosylation of CA15-3 should be a much more sensitive way to assess CA15-3 than the current ELISA method. Linear responses were obtained in the anti-CA15-3 antibody-ConA sandwich assay when sera were diluted up to 2000-fold. This dilution factor is comparable with that of the current ELISA system which allows 50- to 100-fold serum dilutions. The glycosylation level of CA15-3 was found to increase with increasing breast cancer stage in the sandwich assay. The assay system appeared to efficiently discriminate breast cancer stage I (sensitivity: 63%, specificity: 69%), IIA (sensitivity: 77%, specificity: 75%), IIB (sensitivity: 69%, specificity: 86%) and III (sensitivity: 80%, specificity: 65%) from benign breast disease. The antibody-lectin sandwich assay shows promise as a new prospect for the early detection of breast cancer.

The noise of quantum dot infrared photodetectors (QDIPs) can bring about the degradation on their performance, so keen interest has been paid to research on the noise in recent years. In this paper, a noise model of QDIP including the common influence of the microscale and the nanoscale electron transport to the activation energy is further verified at different temperatures, moreover, with the consideration of the dependence of the drift velocity on the electric field. The main concern is to investigate the influence of QDIPs parameters on the noise characteristics, such as the electric field, temperature, two electrons transport, detector material and structural performance parameters, respectively. The reasons for the influence of main performance parameters on the noise are analyzed and discussed in detail. The calculated and simulated results show that the noise model has a good agreement with the experimental data, and the research can provide the guidance in the optimization of the device design and the pursuit of the higher performance QDIP.

The L1 protein is a major component of prophylactic human papillomavirus (HPV) vaccines. Little effort has been made to improve the productivity of L1 protein by optimizing cell culture conditions although the high price of the vaccines is considered one of the factors limiting its widespread use. In biopharmaceutical manufacturing, strategies for optimizing culture conditions tend to focus on improvements in upstream processing rather than final yield because of the complexities of purification procedures. In this study, we investigated L1 protein productivity as a function of the composition of the carbon source and the point of cell harvesting in the Saccharomyces cerevisiae expression system. We performed 44 series of purifications and achieved the highest productivity when the cells were cultured in a medium composed of 7% glucose and 1% galactose for 144 h. The final yield of L1 protein was markedly affected by the glucose: galactose ratio and the point at which cells were harvested: there was a 15-fold difference between the lowest and highest yields. We believe that optimization of the composition of the carbon source and the time of cell harvest have considerable potential for reducing the cost of production of HPV L1 protein.

Elevated plasma levels of LDL and lipoprotein (a) [Lp(a)] are associated with an increased risk of atherosclerosis and coronary heart disease. However, it is not known whether Lp(a) would enhance the atherogenic effect of LDL on coronary atherosclerosis and myocardial infarction. To address this issue, we cross-bred human Lp(a) transgenic (Tg) rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and evaluated the long-term (at the age of 2 years) effects of Lp(a) on the development of coronary atherosclerosis. Compared to non-Tg WHHL rabbits, Tg WHHL rabbits did not show significant changes in plasma total cholesterol, triglycerides, or HDL-C. However, Tg WHHL rabbits showed significantly larger lesions in the right coronary arteries (p

Botulinum neurotoxin produced by Clostridium botulinum type B is in the form of a complex of 12S and 16S toxins. Food-borne botulism is caused by these complex toxins which are ingested orally and absorbed from the digestive tract. Here, we show that the human milk SIgA binds to the type B16S toxin. The binding of SIgA to 16S toxin and HA was inhibited by carbohydrates such as galactose, suggesting that the interaction of carbohydrate side chain of the SIgA with the HA of the 16S toxin is important for SIgA-16S complex formation. We also demonstrate that SIgA inhibits the attachment of 16S toxin to intestinal epithelial cells. These data suggest that the interaction of antigen nonspecific SIgA with 16S toxin has a large influence on the absorption of 16S toxin from the intestinal epithelium, and that SIgA may provide insight into developing a therapeutic agent for type B food-borne botulism.

Botulinum neurotoxin produced by Clostridium botulinum type B is a complex of 12S and 16S toxins. 12S toxin consists of a neurotoxin and a nontoxic non-HA (NTNH). The 16S toxin consists of a neurotoxin, an NTNH, and a hemagglutinin (HA). Food-borne botulism is caused by these complex toxins, which are ingested orally and absorbed from the digestive tract across the epithelial barrier lining the gut.Here we show that the type B 16S toxin, but not the 12S toxin or the neurotoxin, binds to the T84 human intestinal epithelial cell line. We also demonstrate that the HA moiety in the 16S toxin mediates the toxin binding to the cells. The carbohydrates containing a galactose moiety inhibited the binding of the 16S toxin to the T84 cells, and neuraminidase treatment of the cells increased the 16S toxin binding. The binding of the 16S toxin to the neuraminidase-treated cells was also inhibited by carbohydrates containing a galactose moiety. These results suggest that the type B 16S toxin binds to human intestinal epithelial cells via the galactose moiety in the carbohydrate chain on the cell surface.

Background: The Pap test has been used for over 50 years for primary screening of cervical cancer. There has been no study of glycosylation changes in Pap test samples despite considerable potential of the glycosylation changes as biomarkers for detecting cancerous lesions. In this study, we developed a 96-well platform for enzyme-linked lectin assays (ELLAs) to evaluate glycosylation levels in cervical cells. Methods: A total of 117 samples of exfoliated cervical cells (ECCs) from 37 individuals with normal cytology, 20 with cervical intraepithelial neoplasia (CIN) 1, 19 with CIN 2, 26 with CIN 3 and 15 with cervical cancer were analyzed by ELLAs. The wells of 96-well plates were coated with lysates of the cervical cells, and sialylation and fucosylation levels were compared between the groups. Results: Sialylation levels increased and fucosylation levels decreased with increasing grade of cervical dysplasia. ELLAs for sialylation [ELLA-Sambucus nigra (SNAs)] and fucosylation [ELLA-Aleuria aurantia lectin (AAL)] discriminated not only CIN 2 and worse (CIN 2+: CIN 2, CIN 3, and cancer) from normal cytology but also CIN 3 and worse (CIN 3+: CIN3 and cancer) from normal cytology. ELLA-SNAs and ELLA-AALs distinguished cancer from normal cytology with a high true-positive rate (TPR) (ELLA-SNAs: 87%; ELLA-AALs: 87%) and low false-positive rate (FPR) (ELLA-SNAs: 19%; ELLA-AALs: 11%). Conclusions: The sialylation and fucosylation levels of ECCs as measured by ELLAs have great potential as biomarkers for primary screening of cervical cancer.

Licorice (glycyrrhiza uralensis) is known as an herb with detoxication, and it has been widely used in clinical prescription of Oriental herbal medicine. Studies on the effects of licorice in the reproductive system were very rare, especially in spermatogenesis. In order to elucidate the effects of licorice on spermatogonial proliferation and spermatocyte differentiation during neonatal mice spermatogenesis, the organ culture model of testis tissue from neonatal C57BL/6N mice (born 6 d) was established. Then, in the presence of licorice extract (LE), the proliferation activity of spermatogonia was identified with the positive rate quantitative analysis of 5-bromo-2-deoxyuridine (BrdU) and anti-proliferating cell nuclear antigen (PCNA) antibody by immunohistochemical staining. The results showed that, compared to the control group, the percentage of positive cells by BrdU staining enhanced dramatically and that the expression of PCNA protein increased significantly in the spermatogonia from the LE group and showed a concentration-dependent manner (P < 0.05). This indicated that the LE can significantly promote the proliferation of spermatogonia in the spermatogenesis of neonatal mice. Furthermore, proteins related to spermatocyte differentiation, synaptonemal complex protein 3 (SCP3) and meiotic recombinant protein Spo11, were detected by immunohistochemical staining. The results showed that the differentiated spermatocyte in the LE group was significantly increased compared with that of the control group and showed a concentration-dependent manner (P < 0.05). The above results suggested that the LE can significantly accelerate the proliferation of spermatogonia and the differentiation of spermatocytes in the testicular tissue of the neonatal mice, which may be a potential drug for male infertility.

In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression.

Clostridium botulinum type C 16S progenitor toxin consists of a neurotoxin (NTX), a non-toxic non-HA (NTNH), and a haemagglutinin (HA). The HA acts as an adhesin, allowing the 16S toxin to bind to intestinal epithelial cells and erythrocytes. In type C, these bindings are dependent on sialic acid. The HA consists of four distinct subcomponents designated HA1, HA2, HA3a and HA3b. To identify the binding subcomponent(s) of HA of type C 16S toxin, all of the HA-subcomponents and some of their precursor forms were produced as recombinant proteins fused to glutathione S-transferase (GST). These proteins were evaluated for their capacity to adhere to intestinal epithelial cells of guinea pig and human erythrocytes. GST-HA1, GST-HA3b and GST-HA3 (a precursor form of HA3a and HA3b) bound intestinal epithelial cells and erythrocytes, whereas GST alone, GST-HA2 and GST-HA3a did not. GST-HA3b and GST-HA3 showed neuraminidase-sensitive binding to the intestinal epithelial cells and erythrocytes, whereas GST-HA1 showed neuraminidase-insensitive binding. TLC binding assay revealed that GST-HA3b and GST-HA3 recognized sialosylparagloboside (SPG) and GM3 in the ganglioside fraction of the erythrocytes, like native type C 16S toxin [Inoue, K. et al. (1999). Microbiology 145, 2533-2542]. On the other hand, GST-HA1 recognized paragloboside (PG; an asialo- derivative of SPG) in addition to SPG and GM3. Deletion mutant analyses of GST-HA3b showed that the C-terminal region of HA3b is important for its binding activity. Based on these data, it is concluded that the HA component contains two distinct carbohydrate-binding subcomponents, HA1 and HA3b, which recognize carbohydrates in different specificities.

Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized (129)Xe MRI, which can evaluate gas exchange between the alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice, and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease of the fD value in low-density areas with micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.

Tetraspanins organize protein complexes in tetraspanin-enriched membrane microdomains that are distinct from lipid rafts. Our previous studies suggested that reduction in the levels of tetraspanins CD9 and CD81 may be involved in the progression of inflammatory lung diseases, especially COPD. To search for agents that increase the levels of these tetraspanins, we screened 1,165 drugs in clinical use and found that statins upregulate CD9 and CD81 in RAW264.7 macrophages. The lipophilic statins, fluvastatin and simvastatin, reversed LPS-induced downregulation of CD9 and CD81, simultaneously preventing TNF-α and matrix metalloproteinase-9 production and spreading of RAW264.7 cells. These statins exerted anti-inflammatory effects in vitro in wild-type macrophages but not in CD9 knockout macrophages, and decreased lung inflammation in vivo in wild-type mice but not in CD9 knockout mice, suggesting that their effects are dependent on CD9. Mechanistically, the statins promoted reverse transfer of the LPS-signaling mediator CD14 from lipid rafts into CD9-enriched microdomains, thereby preventing LPS receptor formation. Finally, upregulation of CD9/CD81 by statins was related to blockade of GTPase geranylgeranylation in the mevalonate pathway. Our data underscore the importance of the negative regulator CD9 in lung inflammation, and suggest that statins exert anti-inflammatory effects by upregulating tetraspanin CD9 in macrophages.

Tetraspanins have emerged as key players in malignancy and inflammatory diseases, yet little is known about their roles in angiogenesis, and nothing is known about their involvement in lymphangiogenesis. We found here that tetraspanins are abundantly expressed in human lymphatic endothelial cells (LEC). After intrathoracic tumor implantation, metastasis to lymph nodes was diminished and accompanied by decreased angiogenesis and lymphangiogenesis in tetraspanin CD9-KO mice. Moreover, lymphangiomas induced in CD9-KO mice were less pronounced with decreased lymphangiogenesis compared with those in wild-type mice. Although mouse LEC isolated from CD9-KO mice showed normal adhesion, lymphangiogenesis was markedly impaired in several assays (migration, proliferation, and cable formation) in vitro and in the lymphatic ring assay ex vivo. Consistent with these findings in mouse LEC, knocking down CD9 in human LEC also produced decreased migration, proliferation, and cable formation. Immunoprecipitation analysis demonstrated that deletion of CD9 in LEC diminished formation of functional complexes between VEGF receptor-3 and integrins (α5 and α9). Therefore, knocking down CD9 in LEC attenuated VEGF receptor-3 signaling, as well as downstream signaling such as Erk and p38 upon VEGF-C stimulation. Finally, double deletion of CD9/CD81 in mice caused abnormal development of lymphatic vasculature in the trachea and diaphragm, suggesting that CD9 and a closely related tetraspanin CD81 coordinately play an essential role in physiological lymphangiogenesis. In conclusion, tetraspanin CD9 modulates molecular organization of integrins in LEC, thereby supporting several functions required for lymphangiogenesis.

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined.To investigate the role of tetraspanin CD151 in pulmonary fibrosis.CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF.A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF.CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Green's relations have played a fundamental role in the development of semi group theory. M.P. Grillet defined Green's relations on a semiring in terms of principal ideals. In this paper, we mainly discuss the properties of left (right) Green's relations on a semiring, the result show that La is the same as (a] whenever (a] is the minimal left ideal, and we give a sufficient and necessary condition for L = L.

The National Imagery Interpretability Rating Scale (NIIRS) is a 10-level scale (0 to 9) of imagery interpretability, these criteria indicate the level of information that can be extracted from an image of a given interpretability, the lowest is Level 0 and the highest is Level 9. The General Image Quality Equation (GIQE) is a model that relates physical parameters of an imaging sensor to NIIRS rating of the sensors image products. The scale has become an important tool for defining image requirements, selecting and tasking imaging system. In this paper, we first introduce briefly NIIRS and GIQE, and make an initial analysis about the factors affecting perceived interpretability of imagery, such as ground sample distance(GSD), relative edge response(RER), height overshoot(H), noise gain(G), and signal-to-noise ratio(SNR). Then, the design parameters of infrared remote sensor and GSD, RER, H, SNR, and NIIRS scale quantitative relation is first determined, and the simulation curve of NIIRS scale versus R is presented. Finally, the analysis between NIIRS scale and GSD, RER, H and G/SNR shows that it is evident that the GSD and RER are the dominant terms in the equation, and that the overshoot H and the G/SNR have a much smaller impact. Comparisons with calculation results show that the research can provide preliminary theory evidence for the optimum design of remote-sensors although more validation experiments are needed.

Chronic obstructive pulmonary disease is frequently complicated with comorbidities, such as cardiovascular disease, osteoporosis, and body weight loss, but the causal link remains unclear.To investigate the role of adiponectin in the pathogenesis of chronic obstructive pulmonary disease and its potential use in therapy.Adiponectin localization and dynamics in the lung were analyzed in an elastase-induced emphysema model. Next, the lung of adiponectin-knockout mice, extrapulmonary effects, and the underlying mechanism were investigated. Finally, we tested whether exogenous adiponectin could ameliorate the emphysematous change in adiponectin-knockout mice.Adiponectin expression in lung vasculature and plasma concentration of adiponectin were reduced after elastase-instillation. Notably, adiponectin-knockout mice showed progressive alveolar enlargement and increased lung compliance. They further exhibited not only systemic inflammation, but also extrapulmonary phenotype, such as body weight loss, fat atrophy, and osteoporosis. Moreover, endothelial apoptosis was enhanced in the lungs of adiponectin-knockout mice, as evidenced by caspase-3 activity. Consistent with this, expressions of vascular endothelial growth factor receptor-2 and platelet endothelial cell adhesion molecule-1 on endothelial cells were decreased in the adiponectin-knockout mice. Finally, adenovirus-mediated adiponectin supplementation ameliorated the emphysematous phenotype.Adiponectin-knockout mice develop progressive chronic obstructive pulmonary disease-like phenotype with systemic inflammation and extrapulmonary phenotypes. Hypoadiponectinemia could thus play a critical role in the progression of chronic obstructive pulmonary disease and concomitant comorbidities through endothelial dysfunction. Together, adiponectin could be a novel target for chronic obstructive pulmonary disease therapy.

It is very crucial to study financial products in view of financial products emerge in endlessly along with development of the financial market. So, it receives more and more attention from the society about researching how to manage financial assets seriously and scientifically and how to measure asset risk. Now, Application of software MATLAB in the financial area has received much more attention. Both mean-variance and stochastic simulation method are adopted to analyze risk of asset portfolio and income from application of MATLAB in view of asset portfolio, which looks forward to provide reference for efficient frontier of the investment portfolio.

Service economy will be a dominant position in the global economy, but the theory of service economy research is far behind the reality. Service science is conducted to provide theoretical basis and the analysis framework for the service economy. Concept of object and characteristics of the service science are discussed, and challenges and opportunities faced by development of the service science are analyzed.

Botulinum neurotoxin's nontoxic HA protein binds E-cadherin to disrupt cell–cell adhesion in a species-specific manner., Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the nontoxic components, disrupts the intercellular epithelial barrier; however, the mechanism underlying this phenomenon is not known. In this study, we identified epithelial cadherin (E-cadherin) as a target molecule for HA. HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion. Although HA binds human, bovine, and mouse E-cadherin, it does not bind rat or chicken E-cadherin homologues. HA does not interact with other members of the classical cadherin family such as neural and vascular endothelial cadherin. Expression of rat E-cadherin but not mouse rescues Madin–Darby canine kidney cells from HA-induced tight junction (TJ) disruptions. These data demonstrate that botulinum HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion in a species-specific manner and that the HA–E-cadherin interaction is essential for the disruption of TJ function.

Economic security has been a serious problem which threatens and hampers the sustainable growth of the economy. The paper sets up appraising indicator system of economic security on the basis of PSR model, and researches economic security for 21 coal cities by using BP artificial neural net. As innovation of researching economic security, BP artificial neural net has the better ability in level identification, and has application in researching economic security of cities. The conclusion was drawn that the economic security level identification of coal cities was low, and economic security level showed a more regional characteristic.

VAT occupies considerable proportion in our tax categories. It is crucial important to choose VAT mode of adapting our national conditions and economic situation. Our country has implemented production value-added tax since reformed the tax system in 1994. With China's economic unceasing development, implementation of production model VAT has not met with the requirements for present spurring investment, expanding domestic demand and enhancing the competitiveness of enterprises in our country, even it has become obstacle factors of economic development. More than 100 billion tax costs questions for the transformation of VAT cannot be ignored, therefore, the transformation of value-added tax is imperative. Tax costs questions of the VAT have direct respect to exert VAT efficiency, and then affect success or failure of the transformation of VAT work. Start from present situations of the tax costs of VAT transforming, analyze reasons of high costs for tax costs of the VAT, build game model of the tax costs between tax leviers and taxpayers, and then put forward reducing tax costs methods of production type VAT.

Watanabe heritable hyperlipidemic (WHHL) rabbit is an animal model for human familial hypercholesterolemia. Recently, we segregated a new mutant of WHHL rabbits with plasma levels of triglycerides (TG) >500 mg/dl (designated as TGH-WHHL). To investigate the underlying mechanisms for hypertriglyceridemia, we compared TGH-WHHL with WHHL rabbits with lower plasma TG levels (

Orally ingested botulinum neurotoxin (BoNT) causes food-borne botulism, but BoNT must pass through the gut lining and enter the bloodstream. We have previously found that type B haemagglutinin (HA) proteins in the toxin complex play an important role in the intestinal absorption of BoNT by disrupting the paracellular barrier of the intestinal epithelium, and therefore facilitating the transepithelial delivery of BoNT. Here, we show that type A HA proteins in the toxin complex have a similar disruptive activity and a greater potency than type B HA proteins in the human intestinal epithelial cell lines Caco-2 and T84 and in the canine kidney epithelial cell line MDCK I. In contrast, type C HA proteins in the toxin complex (up to 300 nM) have no detectable effect on the paracellular barrier in these human cell lines, but do show a barrier-disrupting activity and potent cytotoxicity in MDCK I. These findings may indicate that type A and B HA proteins contribute to the development of food-borne botulism, at least in humans, by facilitating the intestinal transepithelial delivery of BoNTs, and that the relative inability of type C HA proteins to disrupt the paracellular barrier of the human intestinal epithelium is one of the reasons for the relative absence of food-borne human botulism caused by type C BoNT.

Food-borne botulinum neurotoxin (BoNT) in the gastrointestinal lumen must cross an epithelial barrier to reach peripheral nerves to mediate its toxicity. The detailed mechanism by which BoNT traverses this barrier remains unclear. We found that hemagglutinin (HA) proteins of type B BoNT complex play an important role in the intestinal absorption of BoNT, disrupting the paracellular barrier of intestinal epithelium, which facilitates transepithelial delivery of BoNT both in vitro and in vivo (Matsumura, T., et al., 2008. Cell. Microbiol. 10, 355-364). We also found that type A HA proteins have a similar disrupting activity with a greater potency than type B HA proteins in the human intestinal epithelial cell lines Caco-2 and T84. In contrast, type C HA proteins in the toxin complex (up to 300 nM) have no detectable effect on the paracellular barrier in these human cell lines. These results may indicate that types A and B HA contribute to develop the food-borne human botulism by facilitating the intestinal transepithelial delivery of BoNTs.

To investigate the early in vivo response of hepatic stellate cells in biliary fibrosis, we examined rat livers during the first 7 days after bile duct ligation using light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. At day 1 after bile duct ligation, alpha-smooth muscle actin-positive fibroblasts appeared and then increased in number around the proliferating bile ductules. With time, the destruction of the external limiting plate became accentuated because of the invasion of the proliferating bile ductules and periductural fibrosis. At day 7, stromal cells containing fat droplets appeared in the fibrous tissue adjacent to the periportal parenchyma; these are termed denuded hepatic stellate cells. In the fibrous tissue disconnected from the liver parenchyma, the denuded hepatic stellate cells were replaced by myofibroblast-like cells. Meanwhile, the expression of transforming growth factor-beta1 on biliary epithelial cells increased. These results indicate the dual origin of myofibroblasts in experimental biliary fibrosis, the periductural and periductal fibroblasts in the initial stage, and the denuded hepatic stellate cells in the subsequent stage. These two types of stromal cells may undergo myofibroblastic transformation by the transforming growth factor-beta1 secreted by the proliferating biliary epithelial cells.

The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of the haemagglutinin (HA), a non-toxic component of the large 16S BoNT complex. We find that the HA acts in the intestine to disrupt epithelial barrier function by opening intercellular tight and adherens junctions. This allows transport of BoNT and other large solutes into the systemic circulation and explains how the type B BoNT complexes are efficiently absorbed. In vitro, HA appears to act on the epithelial cell via the basolateral membrane only, suggesting the possibility of another step in the absorptive process. These studies show that the 16S BoNT complex is a multifunctional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves.