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Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. Methods A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. Results 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Conclusions Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Simulations of lithium (Li) impurity transport behaviour with a liquid lithium divertor on the EAST tokamak have been performed using the fluid code EMC3-EIRENE and the Monte Carlo code ITCD. The interactions between particles and the wall surface, like the gyration-induced scrape-off effect, sheath acceleration, kinetic self-sputtering and reflection, are typically ignored or simplified in fluid models. In order to uncover the impacts of the scrape-off effect, sheath acceleration, kinetic self-sputtering and reflection on Li distribution, detailed analysis of the density distributions of Li1+ and Li2+ ions at the divertor region have been carried out by ITCD modelling. The newly-upgraded ITCD code can principally reproduce the distribution patterns of Li ions as well as EMC3-EIRENE under identical plasma conditions on EAST. However, due to the scrape-off effect and sheath acceleration, the densities of Li1+ and Li2+ ions simulated by ITCD are evidently reduced compared to the EMC3-EIRENE simulations. The kinetic self-sputtering by redeposited Li particles in ITCD can increase the densities of the Li ions. Moreover, the kinetic reflection database calculated by SRIM code has been employed by ITCD, which leads to an increase in the Li densities compared to the reflection approach used in EMC3-EIRENE. Overall, by adding the aforesaid physical effects in ITCD, the total number of Li ions shows an obvious reduction compared to the EMC3-EIRENE modelling.

Solitary fibrous tumor/hemangiopericytomas (SFT/HPCs) are mesenchymal tumors characterized by “staghorn” blood vessels and collagen deposition. Little is known about SFT/HPCs with papillary architecture. We summarized the clinicopathologic features of 12 patients with papillary SFT/HPCs (8 males and 4 females; median age: 59 years), including 8 previously reported cases. Tumors were present in the meninges (75%, 9/12), adrenal gland (8%, 1/12), orbit (8%, 1/12), or spinal canal (8%, 1/12). Six tumors (50%) had a true papillary architecture with fibrovascular cores and 6 tumors (50%) had a pseudopapillary architecture with vascular cores. Nuclear staining for STAT6 was present in all tested tumors (10/10). RT-PCR indicated NAB2 ex6-STAT6 ex17 fusion in 4 tumors (80%, 4/5) and NAB2 ex4-STAT6 ex2 fusion in 1 tumor (20%, 1/5). Five patients (42%, 5/12), all with tumors in the meninges, developed local recurrence at a median of 61 months after surgery (range: 56–165 months; mean: 88.6 months). These results indicated that the papillary architecture is a morphological form of SFT/HPCs. The recognition of this pattern, with appropriate immunohistochemical analysis and assessment of NAB2-STAT6 fusion, should facilitate the distinction of these rare neoplasms from morphologically similar tumors in the meninges, lung, pleura, and soft tissue.

Importance The clinical characteristics of infectious mononucleosis (IM) in Chinese children have not been evaluated in multicenter studies, and the effectiveness of antiviral treatment are controversial. Objective To investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients. Methods Hospitalized patients with IM were enrolled between 2018 and 2020 in five children’s hospitals in China. The clinical characteristics were compared among four age groups

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is a member of apoptosis inhibition family which suppresses caspase activity. Osteosarcoma tissues have significantly higher BIRC5 and lower microRNA-218 (miR-218) level than adjacent tissues, indicating tumor suppressor role of miR-218 in osteosarcoma. Bioinformatics analysis showed satisfactory targeting correlation between miR-218 and 3'-UTR of BIRC5 mRNA. This study, thus, investigated if dysregulation of miR-218 and BIRC5 affected apoptosis of osteosarcoma cells U2OS.A total of 42 osteosarcoma patients were collected for tumor and adjacent tissues to compare miR-218 and BIRC5 expressions. Dual-luciferase reporter gene assay examined targeted regulation between miR-218 and BIRC5. In vitro cultured U2OS cells were treated with miR-218 mimic and/or si-BIRC5. Caspase-3 activity was measured by spectrometry while flow cytometry was used to test cell apoptosis, plus protein expression assay by Western blot assay.Compared to adjacent tissues, osteosarcoma tissues had significantly depressed miR-218 expression and elevated BIRC5 expression (p0.05). miR-21 targeted 3'-UTR of BIRC5 to suppress its expression. The elevation of miR-218 and/or silencing BIRC5 significantly depressed BRIC5-induced inhibition on caspase-5, and facilitated U2OS cell apoptosis (p0.05).We observed that miR-218 was significantly down-regulated in osteosarcoma tissues, which had elevated BIRC5 expression. MiR-218 targeted and inhibited BIRC5 expression, weakened caspase-5 inhibition by BIRC5, and facilitated U2OS osteosarcoma cell apoptosis.

Many studies showed that long non-coding RNAs (lncRNAs) may serve as prospective markers for patients with malignant cancers, including cervical cancer (CC). In this study, we mainly investigate the functions of lncRNA PTENP1 in the progression of human CC.Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect expression levels of PTENP1, miR-19b and MTUS1 in CC tissues, the adjacent tissues and CC cell lines. The correlations between PTENP1 with miR-19b, miR-19b with MTUS1 and PTENP1 with MTUS1 were analyzed. Overall survival (OS) of patients was analyzed using Kaplan-Meier method. Proliferation capacity was measured by CCK-8 assay and the invasion ability in CC cell line was detected by transwell assay. Western blot (WB) assay was performed to measure protein levels of tissues and CC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between PTENP1 and miR-19b, miR-19b and MTUS1.We found that PTENP1 was reduced in CC tissues and CC cell lines, which predicted the poor diagnosis of CC patients. MiR-19b was increased in CC tissues, which was negatively correlated with PTENP1 in CC tissues. MTUS1 was reduced in CC tissues, which was negatively correlated with miR-19b and positively correlated within PTENP1 CC tissues. Furthermore, PTENP1 overexpression inhibited cell proliferation ability and invasion capacity in HeLa cells, as well as repressed expressions of Cyclin D1, N-cadherin, and Vimentin. Moreover, Luciferase gene reporter assays verified that miR-19b was a direct target miRNA of PTENP1, and MTUS1 was identified as a direct target of miR-19b. In addition, the inhibited cell proliferation and invasion abilities in HeLa cells with p-PTENP1 were eliminated following with miR-19b mimic transfection.According to the results, this study showed that PTENP1 was reduced in CC patients and it was a prognostic factor for CC patients. Furthermore, we firstly uncovered that PTENP1 could inhibit cell proliferation and invasion via miR-19b/MTUS1 in CC patients, which uncovered the tumor-suppressive role of PTENP1 in CC and suggested that it might be a potential target for treating human CC.

The use of non-fuel pellets is desirable for ITER due to its decoupling ELM pacing from fueling. In this paper, the Neutral Gas Shielding Model (Parks et al., Nucl, Fusion 34(1994)417) has been applied to the ablation of Li pellets in the H-mode pedestal region. The results show that the injection velocity of pellets is a more convenient parameter for one to control the deposition profile and location of the injected species in the pedestal. The information obtained from this work can further be used as input for fluid transport codes to track the trajectories of the impurity species or as input for advanced MHD codes for better understanding the non-linear destabilization of ELMs.

Studies of edge plasma and impurity transport with the toroidally and poloidally localized liquid lithium limiter (LLL) on EAST have been performed by the three-dimensional (3D) edge transport code EMC3-EIRENE. The transport behavior of the Li1+ and Li2+ ions shows a non-axisymmetric distribution in the toroidal direction while an axisymmetric distribution is obtained for the Li3+ ions. The spatial structure of the charge state and excitation radiation patterns of lithium impurity can be understood by using field line tracing, which shows that the Li ions with different charge states exhibit different parallel transport behaviors. The 3D line-integrated LiII emission pattern simulated by EMC3-EIRENE shows a reasonable qualitative agreement with the experiment results measured by the CCD camera system on EAST. An unresolved issue in the LLL experiment is that the species emitting the strong visible spectrum observed around the edge plasma region cannot be distinguished by the current experimental diagnostics on EAST. The detailed numerical analysis of the carbon and deuterium emissions has been carried out to resolve this issue. The simulated deuterium emission pattern shows the same qualitative behavior as the experimental observation at the lower divertor region. The strong radiation experimentally observed at the upper divertor region is perhaps due to the mixing of the lithium and deuterium emissions.

To investigate the effect of fertilization practice on dissolved organic nitrogen (DON) in aggregates, the study was conducted and involved four fertilization treatments: no fertilizer; mineral fertilizer (MF); pig manure matched with mineral fertilizer (MFP) and crop straw matched with mineral fertilizer (MFR). The results showed that DON content and storage were the highest in > 5 mm aggregates and were the lowest in 5 mm by 404.7% and 184.4%. In comparison with MFR, DON content and storage in > 5 mm aggregates for MFP were significantly enhanced by 77.5% and 75.0%. A significantly positive linear correlation relationship between DON content and microbial biomass carbon content was observed in aggregates (R-2 = 0.84; P < 0.01). The results suggest that pig manure matched with mineral fertilizer is a preferred strategy for retaining DON nutrient due to enhanced microbial biomass in aggregates on sloping upland of purple soil.

To investigate the effect of low soil pH caused by fertilization on soil available zinc in calcareous soil, this study was conducted based on a long-term experiment consisting of: (a) no fertilization (CT); (b) mineral fertilizer application coupled with 7500 kg/ha of wheat straw (WS-NPK); (c) mineral fertilizer application coupled with 3750 kg/ha of wheat straw (1/2WS-NPK); (d) mineral fertilizer application alone (NPK). Long-term fertilization results in a significant increase in soil DTPA-extractable zinc. However, the increased soil DTPA-extractable zinc is unavailable to crops and mainly confined to 0.25 mm > and 0.25 mm to 1 mm aggregates. Compared to CT, soil DTPA-extractable zinc under fertilization is more than 9.67% and 122.36% higher in 0.25 mm > and 0.25 mm to 1 mm aggregates, respectively. Furthermore, plant-available zinc in the 0–15 cm soil layer and wheat grain zinc are both significantly positive related to soil DTPA-extractable zinc in > 2 mm aggregates. Therefore, plant-available zinc in the 0–15 cm layer is closely associated with DTPA-extractable zinc in > 2 mm aggregates, and the low soil pH caused by longterm fertilization could not enhance plant-available zinc in the surface soil layer nor elevate wheat grain zinc concentration because of the occlusive effect of soil aggregates.

To investigate the effects of returning wheat straw to croplands on soil compaction and nutrient availability, this trial was designed: (1) planted crops without fertilization (NF); (2) natural land without human activities (CT); (3) applied mineral fertilizers in combination with 7500 kg/ha wheat straw (WS-NPK); (4) applied mineral fertilizers in combination with 3750 kg/ha wheat straw (1/2WS-NPK); and (5) applied mineral fertilizers alone (NPK). It is found that, compared with NPK, the soil bulk density in 1/2WS-NPK and WS-NPK both decreased by more than 10% in the 0 cm to 15 cm layer, and by 6.93% and 9.14% in the 15 cm to 20 cm, respectively. Furthermore, in contrast to NPK, the soil available nitrogen in the 0 cm to 25 cm layer in 1/2WS-NPK and WS-NPK were higher by 17.43% and 35.19%, and the soil available potassium were higher by 7.66% and 17.47%, respectively. For soil available phosphorus in the depth of 5 cm to 25 cm, it was higher by 18.51% in 1/2WS-NPK and by 56.97% in WS-NPK, respectively. Therefore, returning wheat straw to croplands effectively improves soil compaction and nutrients availability, and the improvement in soil nitrogen and phosphorus availability is closely related to the amount of wheat straw.

We have performed linear and nonlinear simulations to study the drive mechanism of the quasi-coherent modes (QCM) during the inter-edge localized mode period in HL-2A. With an unstable Resistive-Ballooning mode from linear simulations, the nonlinear simulation has successfully reproduced the QCM inside the separatrix at the outer mid-plane. The poloidal wave number and frequency from fluctuation analysis are almost the same as the experimental results. The phase shift between the electrical potential and the density fluctuation matches. Linear and nonlinear global profile scans show that the QCM is triggered by the density gradient. Based on these scans, some other experimental observations of the QCM are explained.

It was proved that atmospheric non-equilibrium plasma can be deemed as “reaction carrier”, and is an effective method of partial oxidation of methane to methanol and other higher hydrocarbons. In this paper, hydrogen peroxide vapor is selected as oxygen-containing oxidizer and used to activate and convert methane into methanol in an atmospheric dielectric barrier discharge. A detailed axisymmetric 2D fluid model in CH4/H2O/H2O2 gas mixture is developed, with an emphasis on gas-phase plasma chemistry for partial oxidation of methane and methanol formation. Especially, the effect of hydrogen peroxide concentration on the conversion of methane to methanol is studied. The spatial and temporal distributions of various plasma species are shown as a function of hydrogen peroxide concentration. In addition, the main plasma species and reaction pathways governing the production and loss of CH3OH and OH are determined. It is shown that the increasing hydrogen peroxide concentration results in increase of OH and CH3OH production. Hydroxyl appears to play a significant role during the process of methanol synthesis, which is primarily produced by electron-impact dissociation of H2O2 and H2O molecules.

Magnesium hydroxide (Mg(OH)2) micro- and nanostructures have been synthesized by a single step hydrothermal route. Surface morphology analysis reveals the formation of micro- and nanostructures with varying shape and size at different synthesis conditions. Structural investigations by X-ray diffraction (XRD) and transmission electron microscopy (TEM) confirm that the synthesized material is Mg(OH)2with hexagonal crystal structure. An optical band gap of 5.7 eVis determined for Mg(OH)2 nanodisks from the UV‐vis absorption spectrum. A broad emission band with maximum intensity at around 400 nm is observed in the photoluminescence (PL) spectra of Mg(OH)2 nanodisks at room temperature depicting the violet emission, which can be attributed to the ionized oxygen vacancies in the material. Furthermore, Mg(OH)2 has been converted to MgO by calcination at 450 8C. Optical studies of the MgO nanodisks have shown an optical band gap of 3.43 eVand a broadband PL emission in the UV region. Mg(OH)2 and MgO nanostructures with wide-band gap and short-wavelength luminescence emission can serve as a better luminescent material for photonic applications. # 2009 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Zirconium oxide (ZrO2) nanostructures were synthesized by hydrothermal route. Surface morphology analysis depicts the formation of the nanobars and hexagonal-shaped nanodiscs at different synthesis conditions. The structural analysis confirms that the as-synthesized ZrO2 product is of pure monoclinic phase (m-ZrO2) with crystallite size of about 25 nm. The product consists of monodispersed nanoparticles of uniform composition,highpurity,andcrystallinity.TheRamanspectraarequantitativelyanalyzedandtheobservedpeaksareattributedtovariousvibration modes of the m-ZrO2. The UV‐vis absorption spectrum showed a strong absorption peak at about 292 nm and the estimated optical band gap was around 3.57 eV. Photoluminescence (PL) spectrum of ZrO2 nanostructure showed a strong and broad emission peak at around 410 nm at room temperature, which can be attributed to the ionized oxygen vacancy in the material. # 2009 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Recombinant human anti-tumor necrosis factor (TNF)-α scFv-Fc was expressed in TKO mutant Arabidopsis thaliana seeds using plant-specific codons. Immunoblotting using a human IgG1 antibody detected the expression of anti-TNF-α proteins in plants. Results from qRT-PCR analysis demonstrated that the time of harvest significantly affected the protein yield and quality. Our results indicate that the Phaseolus vulgaris β-phaseolin promoter directed anti-TNF-α scFv-Fc expression in A. thaliana seeds, with a maximum yield obtained at 20-days of development. Although the yield of anti-TNF-α scFv-Fc protein was not very high, accumulation of recombinant proteins in seeds is an attractive and simple method that can be used to purify biologically active anti-TNF-α scFv-Fc.

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity. The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmol/kg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor Nomega-nitro--arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney. Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a Kd of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.

BACKGROUND: Despite decades of research the therapeutic outcome of Glioblastoma Multiforme (GBM) remains dismal as no contemporary chemotherapeutic regimen is effective. Recent understanding of the molecular mechanisms behind chemoresistance has focussed on a small population (~1%) of GBM cancer stem cells (CSCs) which promotes therapeutic resistance and local invasion of GBM cells. Evidence indicates that intra-tumoral hypoxia drives CSC phenotypes in solid tumours via epithelial-to-mesenchymal transition (EMT). Hypoxia inducible factors (HIFs), NF-κB and aldehyde dehydrogenase (ALDH) activity are highly up-regulated in hypoxia-induced CSCs, but the insights on how HIFs, NF-κB and ALDH together coordinate the stemness and chemoresistance still remain obscure. Development of drugs that can cross blood brain barrier (BBB) and effectively target the CSCs is of significant importance for GBM chemotherapy. Disulfiram (DS), a clinically used anti-alcoholism drug, is a strong inhibitor of NF-κB and ALDH. Our previous studies show that DS in combination with copper (Cu) can effectively reverse chemoresistance and block metastasis in multiple cancers. In this study we used an in vitro GBM CSC model of NF-κB-p65 and HIFs transfected GBM cell lines to investigate the relationship between hypoxia induced HIFs, NF-κB activation and ALDH activity and their role in chemoresistance. We also examined the in vitro cytotoxicity and the molecular mechanism of action of DS/Cu on GBM CSCs. Although DS is very effective in suppressing GBM in vitro, its clinical application is severely limited by its short half-life in the bloodstream. We recently developed and characterized a poly lactic-co-glycolic acid (PLGA)-encapsulated DS nanoparticles, protecting DS from the degradation in the bloodstream. We evaluated the in vivo efficacy of the PLGA-DS nanoparticles in subcutaneous and orthotopic xenograft glioma mouse models. RESULTS: GBM cells grown as spheres showed vast proportion of hypoxic cells with elevated CSC and EMT markers suggesting hypoxia induced EMT. GBM-CSCs are chemoresistant and displayed increased levels of HIFs, NF-κB and ALDH activity. GBM cells transfected with NFκB-p65 and HIFs exhibited CSC markers and chemoresistance indicating their pivotal role in maintaining CSC phenotypes. DS/Cu is cytotoxic to GBM cell lines and completely eradicated CSCs at low nanomolar levels. DS/Cu inhibits NF-κB and ALDH activity and triggers intrinsic apoptotic pathway. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited GBM tumour in both subcutaneous and orthotopic xenograft mouse models at a very low dose (

This paper presents an analytical approach for investigating the dynamics and stability of an outer cylindrical shell conveying viscous fluid (i.e. water) in the annulus between the inner shell-type body and the outer shell with thermal load. The steady viscous forces that induce prestress on the shells are determined based on the time–mean Navier–Stokes equations. The shell motions are described by Flügge’s shell equations incorporating the prestress arising from the viscous effect. The shell-vibration-induced fluid forces are described by means of the potential flow theory, and the thermal loads are determined by the thermoelastic theory. The analytical model is conducted by the zero-level contour method with the aid of the weighted residual technology. The present study shows that the effect of viscosity in the annular flow renders the system more unstable. Moreover, the thermal load tends to reduce the critical flow velocity pronouncedly, for which there exists a critical temperature rise.

The basal transcription of the CXC chemokine, melanocyte growth stimulatory activity (MGSA)/growth-regulated protein (GRO)-alpha, is up-regulated in Hs294T melanoma cells compared with the normal retinal pigment epithelial (RPE) cells. Previous studies characterized a cytokine-inducible, functional nuclear factor (NF)-kappaB consensus element in the immediate 5' regulatory region of the MGSA/GRO-alpha gene at -78 bp. Although the cytokine-inducible mechanisms for transcription of this gene are fairly well delineated, the mechanisms involved in its basal up-regulation of transcription in Hs294T melanoma cells are poorly understood. Recently, we demonstrated an increased rate of IkappaB-alpha degradation in Hs294T cells, which leads to an increased nuclear localization of NF-kappaB (R. L. Shattuck-Brandt and A. Richmond. Cancer Res., 57: 3032-3039, 1997). Here we demonstrate that Hs294T melanoma cells have elevated basal IkappaB kinase (IKK) activity relative to RPE cells, causing an increased constitutive IkappaB-alpha phosphorylation and degradation. We also show here that the resultant elevated nuclear NF-kappaB (p50/p65) in these cells is responsible for the increased basal transcription of MGSA/GRO-alpha. Pretreatment of Hs294T or RPE cells with proteasome inhibitors MG115 or MG132 captures the slower migrating, constitutively phosphorylated form of IkappaB-alpha in Hs294T melanoma cells, but not in RPE cells. In addition, a phospho-specific antibody that specifically recognizes the inhibitory form of IkappaB that is phosphorylated at Ser-32 reacted with IkappaB-alpha in Hs294T cell, but not in unstimulated RPE cells. Although the basal level of protein expression of IKK-alpha or IKK-beta are the same in both Hs294T and RPE cells, immunoprecipitation with IKK-alpha antibody combined with activity assay reveal a constitutively active IKK complex in Hs294T melanoma cells. Cotransfection of a 350-bp MGSA/GRO-alpha promoter-luciferase reporter construct with either the dominant negative IKK-alpha or the repressors of NF-kappaB, the IkappaB-alpha wild type or mutants lacking the inducible phosphorylation sites, demonstrates that the increased basal MGSA/GRO-alpha transcription in the Hs294T cells is due to the enhanced nuclear activation of NF-kappaB.

p190 is a Tyr-phosphorylatable G protein of M(r) 190,000 that binds NH2-terminal SH2 domains of GAP1, a Ras GAP of M(r) 120,000. p190 contains at least two functional domains: a GTPase domain at the NH2 terminus and a GAP domain at the COOH terminus that can attenuate signal-transducing activity of three distinct G proteins (Rac, Rho, and CDC42). Here, we demonstrate that overexpression of either an antisense p190 RNA or a dominant negative mutant (Asn36) of p190 GTPase domain (residues 1-251) but not the wild-type p190 GTPase domain is able to transform normal NIH/3T3 fibroblasts. Furthermore, overexpression of either the wild-type p190 GTPase domain or the COOH-terminal GAP domain can suppress v-Ha-Ras-induced malignant transformation. These results indicate that p190 contains at least two distinct anti-Ras tumor suppressor domains, the GTPase and GAP domains, and suggest that one of the mechanisms underlying the suppression of Ras-transformation by p190 is the attenuation by p190 GAP domain of Rac/Rho/CDC42 signalings, which are essential for Ras-transformation. In fact, the p190 GAP domain alone suppresses the expression of the c-Fos gene, which is mediated by Rac/Rho/CDC42 and is required for oncogenicity of Ras.

In an effort to isolate novel genes that may be involved in the development of the cardiac cushions and then the formation of cardiac valves and septa, we utilized the differential mRNA display method in conjunction with the whole-mount in situ hybridization. The total RNAs used to differentially display were prepared from atrioventricular (AV) canal regions of stage 15 and stage 21 chicken hearts because critical events known to be important for the AV valve and septum formation occur during this period of the development. We have successfully obtained 14 potential candidate genes. Three examples, 15H16 (phospholamban), E13 (skeletal alpha-tropomyosin) and 21C (a novel gene), are discussed here. Levels of mRNA expression in developing hearts were determined by Northern blot analysis and their expression patterns were revealed and compared using whole-mount in situ hybridization. Both phospholamban and skeletal alpha-tropomyosin messages in the myocardium of the AV canal region showed significant decrease during this period of the development. The 21C differential display product detects a novel 9.5 Kb message whose expression is cardiac-specific at early stages of development. The expression level of the 21C gene appeared to be increased from stage 15 to stages 21 and 25 as determined by both Northern blot analysis and in situ hybridization. From these data, we demonstrate that the differential display method together with the whole-mount in situ hybridization could be an effective means for the isolation of novel and differentially expressed genes.

Two kinds of distinctive field emission behaviors were observed on vertically aligned multiwall carbon nanotube ~CNT! films grown by hot filament dc-plasma enhanced chemical vapor deposition. Some samples have stable emission current for more than 60 h ~type I!, while others degrade substantially in the first 16 h ~type II!. During the field emission measurement, a brief exposure to air led an abrupt decrease of emission current of all samples. But subsequent reevacuation made type I samples recover the emission current fully, whereas type II samples were damaged permanently reflecting on the irrecoverable emission current. Microstructure studies by transmission electron microscope clearly showed that the stable emission is due to a surface passivation of CNTs by a thin layer of amorphous carbon that prevents CNTs from reacting with ambient gases, e.g., oxygen, during air exposure. © 2004 American Institute of Physics. @DOI: 10.1063/1.1642272#

An ocular renin-angiotensin system has been implicated in the proliferation of retinal blood vessels and blindness in diabetes mellitus. Its cellular basis has not been established. The objective was to identify sites of renin synthesis, secretion, and processing in eyes from humans, BALB/c mice, Sprague-Dawley rats, and a hypertensive transgenic rat model (mREN-2) that displays amplified extrarenal renin synthesis.Paraffin sections of eyes were incubated with antisera to renin protein, prorenin, vimentin, and Müller cells. Enzyme kinetic renin assay was performed on extracts of whole eyes (excluding lens and vitreous) and comparisons made with adrenal glands and kidneys. For detection of renin mRNA, retinas were separately pooled from BALB/c and Swiss mice.In normal rodent and autopsy human eyes, labeling for renin, vimentin, and Müller cell protein was observed in the cytoplasm of all macroglial Müller cells, with renin labeling most obvious in endfeet closely apposed to retinal blood vessels. Prorenin labeling was not detected. Less intense renin labeling, again without prorenin, was seen in nonpigmented ciliary epithelium of rodents. In transgenic (mREN-2) rat eyes, renin and prorenin labeling of Müller cells and nonpigmented ciliary epithelium were intense. Prorenin was localized to the posterior region of Müller cells but only sparsely to endfeet in rodent retinas, and renin was present only in an active form in amounts one third that of one adrenal. Renin mRNA was readily detected. In human retina, renin was present in active and pro-forms, and the total amount was approximately one fiftieth that of adrenal.Renin is synthesized in the retina and is specifically localized to the macroglial Müller cells. Nonpigmented ciliary epithelium also contains renin. The presence of prorenin in the posterior part of the Müller cell, with active renin throughout but notably in endfeet in apposition to retinal capillaries, suggests directional processing of renin. These findings are consistent with earlier suggestions that retinal neovascularization may be associated with Müller cell dysfunction.

The bradykinin B2 receptor (B2R) mediates most of the biological effects of kinins. In the present study, we have cloned and sequenced the gene (B2R) from a mouse embryonic stem (ES) cell genomic library. Mouse B2R is 7 kb in length containing three exons of 0.3, 0.23 and 3.7 kb separated by two introns of 2.5 and 0.41 kb. The first and second exons are noncoding while the third exon contains the full-length coding region and a long 3' noncoding region. An ATG translation start codon, TGA stop codon and a polyadenylation signal (AATAAA) were identified in the third exon. B2R encodes a protein of 41,470 Da and 366 amino acids (aa) forming seven transmembrane (TM) domains. At the aa level, B2R shares 91 and 82% sequence identity with the rat and human B2R, respectively. In the 5' flanking region, a consensus TATA box, a putative cAMP-response element, a putative phorbol ester-response element, a putative AP-1-binding site and a putative IL-6-response element were identified. Southern blot analysis following reverse transcription and PCR showed that B2R is expressed in most mouse tissues, except the liver and spleen, which is consistent with the wide distribution of B2R activity as deduced from pharmacological studies.

A study was made in Neijiang City, Sichuan Province to observe the safety and immunogenicity of a live attenuated hepatitis A virus (HAV) vaccine (H2 strain). 3,031 children, aged 6 to 9 years, were injected subcutaneously with 10(6.0) TCID50, 10(5.5) TCID50, and 10(5.0) TCID50 of HAV vaccine; the seroconversion rate and antibody GMT were 97.52%-90.68%, GMT = 1:5.19 +/- 1.90-1:3.36 +/- 1.94; 84.75%-76.27%, GMT = 1:4.29 +/- 1.96-1:2.0 +/- 2.67; 53.23%-51.61%, GMT = 1:2.57 +/- 1.89-1:1.68 +/- 1.41 respectively after 4 weeks to 12 months of inoculation. Forty-eight children in the control group were anti-HAV negative at 4, 8, and 12 weeks; 21 children in the oral group were not antibody positive 4 and 8 weeks after oral administration of the vaccine. The stool specimens of 3 of the 14 vaccinated children were HAA positive. The results suggest that the live attenuated HAV vaccine (H2 strain) is of good immunogenicity and safety.

During the past 10 years, 60 cases of cleft lip with or without cleft palate [CL(P)] were recorded among 45,072 newborns at Shanghai International Peace Maternity and Infant Hospital, China. The incidence was 1.33 per 1,000 births. The family histories of 163 CL(P) patients were analyzed. The incidences of CL(P) in the first-, second-, and third-degree relatives of CL(P) patients were 11/246 (4.47%), 10/1,032 (0.97%), and 6/1,727 (0.35%), respectively. Of the 163 probands, three had a history of consanguinity of the parents (1.8%), in contrast to 0.77% in the general population. These data are suggestive of multifactorial inheritance. The heritability of CL(P) in our study calculated by Falconer's formula was 77.6%.