Oxaliplatin (OxP) has been used in combination therapy with gemcitabine for the treatment of pancreatic cancer (PC) but the beneficial effect was marginal, which is believed to be due to de novo and acquired drug-resistance of PC. Here we report our in vitro and in vivo preclinical evidence in support of chemo-sensitization of drug-resistant cells by a non-toxic chemopreventive agent (genistein). Genistein pretreatment together with low concentration of OxP showed significant reduction in cell viability and colony formation concomitant with increased apoptosis (p<0.01), which was highly synergistic. Drug-resistance of PC is allegedly linked with both constitutive and OxP-induced activation of NF-kappaB, and we found that inactivation of NF-kappaB by genistein prior to treatment of cells with OxP was required for cell killing, which was consistent with the down-regulation of NF-kappaB and its downstream anti-apoptotic genes (Bcl-2 XIAP's, survivin). Most importantly, our in vivo experiments using orthotopic mouse model showed significant reduction in tumor size (p<0.01) and reduction of locoregional lymph node metastasis by combination treatment. These results were also consistent with inactivation of NF-kappaB and the down-regulation of NF-kappaB downstream genes, decreased proliferation marker (Ki-67), and increased apoptosis (TUNEL) in tumor remnants, all of which was consistent with in vitro findings. From these results, we conclude that genistein sensitizes drug-resistant PC to OxP, which is mechanistically linked with inactivation of NF-kappaB signaling, resulting in greater anti-tumor effects, and thus our data suggest that this approach could be useful in improving the treatment outcome for patients diagnosed with PC. (c) 2010 UICC.

BACKGROUND: Resistance to numerous insecticide classes in Bemisia tabaci Gennadius has impaired field control efficacy in south-eastern China. The biotype and resistance status of B. tabaci collected from these areas was investigated.RESULTS: Two different biotypes of B. tabaci (B-biotype and Q-biotype) were detected in south-eastern China, and the samples collected from geographical regions showed a prevalence of the Q-biotype and the coexistence of B- and Q-biotypes in some regions. Moderate to high levels of resistance to two neonicotinoids were established in both biotypes (28-1900-fold to imidacloprid, 29-1200-fold to thiamethoxam). Medium to high levels of resistance to alpha-cypermethrin (22-610-fold) were also detected in both biotypes. Four out of 12 populations had low to medium levels of resistance to fipronil (10-25-fold). Four out of 12 populations showed low levels of resistance to spinosad (5.7-6.4-fold). All populations tested were susceptible to abamectin.CONCLUSION: The Q-biotype B. tabaci is supplanting the B-biotype which used to be ubiquitous in China. Field populations of both B- and Q-biotypes of B. tabaci have developed high levels of resistance to imidacloprid and thiamethoxam. Abamectin is the most effective insecticide against adult B. tabaci from all populations. Copyright (c) 2010 Society of Chemical Industry.

In continuing our program aimed to search for potent drugs for bacterial infections, a series of 3-(4-halophenyl)-3-oxopropanal and their derivatives were designed, synthesized and their antibacterial activities in vitro against both Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa were evaluated. Compounds 7, 8, 13-16, 21 and 22 had moderate antibacterial activities against Staphylococcus aureus (minimal inhibitory concentration (MIC) <16 microg/ml), suggesting that the introduction of mono-methoxyamine or ethoxyamine moiety might play an important role in determining the potent antibacterial activities. Furthermore, the antibacterial activities of select compounds 7, 15 and 16 against the clinically important pathogenic bacteria-methicillin-resistant Staphylococcus aureus (MRSA) were also investigated. Results showed that these compounds exhibited more potent activities than the well-known antibacterial agents Houttuynin and Levofloxacin.

MOTIVATION: A wealth of protein-protein interaction (PPI) data has recently become available. These data are organized as PPI networks and an efficient and biologically meaningful method to compare such PPI networks is needed. As a first step, we would like to compare observed networks to established network models, under the aspect of small subgraph counts, as these are conjectured to relate to functional modules in the PPI network. We employ the software tool GraphCrunch with the Graphlet Degree Distribution Agreement (GDDA) score to examine the use of such counts for network comparison. RESULTS: Our results show that the GDDA score has a pronounced dependency on the number of edges and vertices of the networks being considered. This should be taken into account when testing the fit of models. We provide a method for assessing the statistical significance of the fit between random graph models and biological networks based on non-parametric tests. Using this method we examine the fit of Erdös-Rényi (ER), ER with fixed degree distribution and geometric (3D) models to PPI networks. Under these rigorous tests none of these models fit to the PPI networks. The GDDA score is not stable in the region of graph density relevant to current PPI networks. We hypothesize that this score instability is due to the networks under consideration having a graph density in the threshold region for the appearance of small subgraphs. This is true for both geometric (3D) and ER random graph models. Such threshold behaviour may be linked to the robustness and efficiency properties of the PPI networks. CONTACT: tiago@stats.ox.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

15-Hydroxyeicosatetrenoic acid (15-HETE) is an important product of arachidonic acid catalyzed by 15-lipoxygenase (15-LO) in the wall of pulmonary vessels, which plays a key role in pulmonary arterial hypertension. The previous studies showed that 15-HETE inhibits apoptosis. It is still unknown, however, whether 15-HETE acts on the apoptotic responses through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. The aim of the study is to test the hypothesis that ERK1/2 pathway participates in the protective effects of 15-HETE on the cell survival. This hypothesis was validated by cell viability measurement, nuclear morphology determination, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, mitochondrial potentials assay and Western blot. We found that 15-HETE enhanced cell survival, suppressed the expression of phosphatase and tensin homologue deleted on chromosome ten, upregulated X-linked inhibitor of apoptosis protein and Bcl-2 and attenuated mitochondrial depolarization in pulmonary artery muscle smooth cells (PASMCs) under serum-deprived conditions. These effects were reversed by ERK1/2 inhibitor PD98059. Taken together, our data indicated that the ERK1/2 kinase is a regulator of PASMC apoptosis, and potential therapeutical strategy for pulmonary hypertension may be developed by targeting at intracellular signaling systems centered by the kinase.

OBJECTIVE: To establish a method for quick finding the absorption ingredients of Wuzhuyu decoction in order to select the index to control its quality. METHOD: The absorption of three concentration of Wuzhuyu decotion was investigated with the in vitro-everted intestinal sac model. The intestinal bag fluid of jejunum and ileum were collected in different time and the eight ingredients, which were evodiamine (Ev), rutaecarpine (Ru), limonin (Li), ginsenoside-Rb1, -Rg1, -Re (Rb1, Rg1, Re), isorhamnetin-3-O-beta-D-glucosyl(6''-->1'")-alpha-L-rhamnoside (Irs)and 6-gingerol (6-Gi), were detected by HPLC as the represent constituents in samples. RESULT: Eight ingredients except Ru in samples could be detected, but Ev could not be detected in high concentration samples. The ratios between absorption ingredients were different from in Wuzhuyu decotion. CONCLUSION: The in vitro-everted intestinal sac canc absorb the ingredients of Wuzhuyu decotion selectivity. Compare with the ileum, the jejunum can provide the more absorption information and faster, the best test time is 60-90 min.

The chronic toxicity of dietary cadmium to the saltwater cladoceran Moina monogolica Daday and its relative toxicity compared with aquatic exposure were investigated in the present study. The microalgae Chlorella pyrenoidosa, exposed to cadmium in growth inhibition tests, had a 96-h median effective concentration (EC50) of 81.2 microg Cd/L (95% confidence intervals [CIs] = 71.9-95.1). C. pyrenoidosa exposed for 96 h to sublethal dissolved cadmium concentrations in the range 4.10 +/- 0.30 to 70.29 +/- 0.31 microg/L resulted in algal cadmium burdens up to 73.86 x 10(-16) g Cd/cell. Cellular cadmium burdens accumulated in a dose-dependent manner, whereas cell densities inversely declined from 670 x 10(4) to 38 x 10(4) cells/ml with exposure to the increasing aqueous cadmium concentrations. C. pyrenoidosa preexposed to cadmium and used as food in a chronic 21-d toxicity test with the cladoceran M. monogolica, containing no added dissolved cadmium, inhibited reproduction. Significant reductions of the net reproduction rate (R(0)) per brood were observed in all broods, and the decline in the number of neonates produced increased with each subsequent brood. The cadmium concentration (4.10 +/- 0.30 microg/L) in the algal culture water that produced the lowest algal cadmium burden (2.85 +/- 0.76 x 10(-16) g Cd/cell) was shown to inhibit M. monogolica reproduction and was compared with the water quality criteria (WQC) of China. This comparison indicated that dietary exposure to cadmium may cause sublethal responses at concentrations below the current cadmium WQC of China for aquaculture. Environ. Toxicol. Chem. 2010;29:365-372. (c) 2009 SETAC.

The phylogenetic relationships of 13 snapper species from the South China Sea have been established using the combined DNA sequences of three full-length mitochondrial genes (COI, COII and CYTB) and two partial nuclear genes (RAG1, RAG2). The 13 species (genus Lutjanus) were selected after DNA barcoding 72 individuals, representing 20 species. Our study suggests that although DNA barcoding aims to develop species identification systems, it may also be useful in the construction of phylogenies by aiding the selection of taxa. Combined mitochondrial and nuclear gene data has an advantage over an individual dataset because of its higher resolving power.

The objective of this study is to examine whether or not the gains from reduced spraying for bollworms are being sustained more than one decade after the initial adoption in 2007. Based on farm-level data collected by the authors in 1999-2007 in 16 villages from 4 provinces, this study shows that insecticides applied for controlling bollworms have declined. This analysis supports Chinese policy makers' decision to not require refuges of non-Bt cotton fields. It also suggests that past studies may have underestimated the benefits from adopting Bt technology.

Wetlands in the Sanjiang Plain are rich in biodiversity and natural resources in the northeast of China. However, this wetland area has decreased in size and deteriorated in quality owing to expanded agricultural activities since the 1950s. Converting farmlands to wetlands is necessary to improve these conditions. Using Remote Sensing (RS) and Geographic Information Systems (GIS) technologies, we derived farmland productivity data and hydrology data for the Sanjiang Plain. The farmland productivity data were derived from land use and net primary productivity (NPP) data of the MODIS products. We obtained three productivity farmland classes (low, medium, and high) through the NPP anomaly percentage method. We were only concerned with the low-productivity farmland. Hydrology data were modeled with a wetness index, which was derived from Digital Elevation Model (DEM) data. Based on these two data layers, we identified and prioritized sites for the conversion of farmlands to wetlands. The areas with low farmland productivity and medium or high wetness values have potential to support the conversion of farmlands to wetlands. Potential sites were prioritized in terms of patch size and proximity to natural wetlands and water bodies. We obtained three priority classes, among which the high-priority class would be used as the areas for the recent conversion of farmlands to wetlands. The area of this class was 75,888 ha and accounted for 1.3% of the total farmland area.

OBJECTIVE: We examined the utility of distinguishing between patients with frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) using quantitative cerebral blood flow (CBF) imaging with arterial spin labeled (ASL) perfusion MRI. METHODS: Forty-two patients with FTLD and 18 patients with AD, defined by autopsy or CSF-derived biomarkers for AD, and 23 matched controls were imaged with a continuous ASL method to quantify CBF maps covering the entire brain. RESULTS: Patients with FTLD and AD showed distinct patterns of hypoperfusion and hyperperfusion. Compared with controls, patients with FTLD showed significant hypoperfusion in regions of the frontal lobe bilaterally, and hyperperfusion in posterior cingulate and medial parietal/precuneus regions. Compared with controls, patients with AD showed significant hypoperfusion in the medial parietal/precuneus and lateral parietal cortex, and hyperperfusion in regions of the frontal lobe. Direct comparison of patient groups showed significant inferior, medial, and dorsolateral frontal hypoperfusion in FTLD, and significant hypoperfusion in bilateral lateral temporal-parietal and medial parietal/precuneus regions in AD. CONCLUSIONS: Doubly dissociated areas of hypoperfusion in FTLD and AD are consistent with areas of significant histopathologic burden in these groups. ASL is a potentially useful biomarker for distinguishing patients with these neurodegenerative diseases.

The transfection efficiency of wild-type p53 (wtp53) was investigated in retinoblastoma (RB) Y79 cells using an ultrasound microbubble technique. A human RB nude mouse xenograft tumour model was also used to investigate whether this technique could deliver wtp53 into solid tumours. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that wtp53 was successfully transfected into Y79 cells in the plasmid with microbubbles and ultrasound group and in the plasmid with liposomes group, but not in the plasmid with ultrasound group or in the untreated control group. Flow cytometry showed that apoptosis was highest in the microbubbles and ultrasound group (25.58%) compared with the plasmid with liposomes group (19.50%), and the other two groups (< 10%). RT-PCR also showed that the wtp53 gene was successfully transfected into solid tumours in the plasmid with microbubbles and ultrasound group. This study provides preliminary evidence in support of a potential new approach to RB gene therapy.

ABSTRACT: BACKGROUND: To assess the frequency of IMLN recurrence, its associated risk factors with disease-free interval (DFI) and its predicting factors on overall survival time. METHODS: 133 cases of breast cancer IMLN recurrence were identified via the computerized CT reporting system between February 2003 and June 2008, during which chest CT for patients with breast cancer (n=8867) were performed consecutively at Cancer Hospital, Fudan University, Shanghai, China. Patients' charts were retrieved and patients' characteristics, disease characteristics, and treatments after recurrence were collected for analysis. The frequency was 1.5% (133/8867). RESULTS: IMLN recurrence was presented as the first metastatic site in 121 (91%) patients while 88 (66.2%) had other concurrent metastases. Typical chest CT images included swelling of the IMLN at the ipsilateral side with local lump and sternal erosion located mostly between the second and third intercostal space. The median disease-free interval (DFI) of IMLN recurrence was 38 months. The independent factors that could delay the IMLN recurrence were small tumor size (HR 0.5 95%CI: 0.4 - 0.8; p = 0.002), and positive ER/PR disease (HR 0.6, 95% CI: 0.4 - 0.9; p = 0.006). The median survival time after IMLN recurrence was 42 months, with a 5-year survival rate of 30%. Univariate analysis showed four variables significantly influenced the survival time: DFI of IMLN recurrence (p = 0.001), no concurrent distant metastasis (p = 0.024), endocrine therapy for patients with positive ER/PR (p = 0.000), radiotherapy (p = 0.040). The independent factors that reduced the death risk were no concurrent distant metastases (HR: 0.7, 95% CI: 0.4 - 0.9; p = 0.031), endocrine therapy for patients with positive ER/PR status (HR: 0.2, 95% CI: 0.1 - 0.5; p = 0.001) and palliative radiotherapy (HR: 0.3, 95% CI: 0.1- 0.9; p = 0.026). CONCLUSIONS: The risk of IMLN recurrence is low and there are certain characteristics features on CT images. ER/PR status is both a risk factor for DFI of IMLN recurrence and a prognostic factor for overall survival after IMLN recurrence. Patients with only IMLN recurrence and/or local lesion have a good prognosis.

Summary In this study, the distraction length of distraction implant was set as input variable which ranged from 2 to 10 mm. The effect of distraction length on the maximum Von Mises stress in the jaw bones and the implant were evaluated by a finite element method. The results showed that under axial load, the maximum equivalent stresses in cortical bone, cancellous bone, and distraction screw decreased by 5.8%, 8.6%, and 11.0%, respectively, with the changing of distraction length, and under buccolingual load those decreased by 0.3%, 18.0%, and 13.0%, respectively. The data indicate that cancellous bone is more sensitive to distraction length than the cortical bone. Under both loads, the central distraction screw was subjected to the stress concentration and more easily damaged by buccolingual force than by axial force. Distraction implant with distraction length exceeding 8 mm showed relatively better biomechanical behaviour.

Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue repair and modulating immune responses in vitro and in vivo. From April 2005 to October 2008, 19 patients with refractory cGVHD were treated with MSCs derived from the BM of volunteers. The median dose of MSCs was 0.6 x 10(6) cells per kg body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a CR (n=4) or a PR (n=10). The immunosuppressive agent could be tapered to less than 50% of the starting dose in 5 of 14 surviving patients, and five patients could discontinue immunosuppressive agents. The median duration between MSC administration and immunosuppressive therapy discontinuation was 324 days (range, 200-550 days). No patients experienced adverse events during or immediately after MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical improvement was accompanied by the increasing ratio of CD5+CD19+/CD5-CD19+ B cells and CD8+CD28-/CD8+CD28+ T cells. In conclusion, transfusion of MSCs expanded in vitro, irrespective of the donor, might be a safe and effective salvage therapy for patients with steroid-resistant, cGVHD.Bone Marrow Transplantation advance online publication, 6 September 2010; doi:10.1038/bmt.2010.195.

Zinc has a crucial role in the biology of p53 in that p53 binds to DNA through a structurally complex domain stabilized by zinc atom. The p53 negative regulator MDM2 protein also carries a C-terminal RING domain that coordinates two zinc atoms, which are responsible for p53 nuclear export and proteasomal degradation. In this clinically translatable study, we explored the critical role of zinc on p53 reactivation by MDM2 inhibitor, MI-219, in colon and breast cancer cells. ZnCl(2) enhanced MI-219 activity (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), apoptosis and colony formation), and chelation of zinc not only blocked the activity of MI-219, but also suppressed reactivation of the p53 and its downstream effector molecules p21(WAF1) and Bax. N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine (TPEN), a specific zinc chelator, but not 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (Bapta-AM), a calcium chelator, blocked MI-219-induced apoptosis. Nuclear localization is a prerequisite for proper functioning of p53 and our results confirm that TPEN, and not Bapta-AM, could abrogate p53 nuclear localization and it interfered with p53 transcriptional activation. Addition of zinc suppressed the known p53 feedback MDM2 activation, which could be restored by TPEN. Co-immunoprecipitation studies verified that MI-219-mediated MDM2-p53 disruption could be suppressed by TPEN and restored by zinc. As such, single-agent therapies that target MDM2 inhibition, without supplemental zinc, may not be optimal in certain patients owing to the less recognized mild zinc deficiency among the 'at-risk population' as in the elderly who are more prone to cancers. Therefore, use of supplemental zinc with MI-219 will benefit the overall efficacy of MIs and this potent combination warrants further investigation.Oncogene advance online publication, 6 September 2010; doi:10.1038/onc.2010.403.

This study sought to assess whether residual feed intake (RFI) calculated by regressing feed intake (DMI) on growth rate (ADG) and metabolic weight (MWT) in 3 different ways led to similar estimates of genetic parameters and variance components for young growing cattle tested for feed intake in fall and winter seasons. A total of 378 beef steers in 5 cohorts were fed a typical high energy feedlot diet, and had free choice access to feed and water. Feed intake data were collected in fall or winter seasons. Climate data was obtained from the University of Alberta Kinsella meteorological station and Vikings AGCM station. Individual animal RFI was obtained by either fitting a regression model, to each test group separately (RFI(C)), fitting a regression model to pooled data consisting of all cohorts but including test group as a fixed effect (RFI(O)) or fitting a regression to pooled data with test group as a fixed effect but within seasonal (Fall-Winter or Winter-Spring) groups (RFI(S)). Two animal models (M1 and M2) that differed by the inclusion of fixed effects of test group or season, respectively, were used to evaluate RFI measurements. Feed intake was correlated with air temperature, relative humidity, solar radiation and wind speed, but the nature and magnitude of the correlations were different for the two seasons. Single trait direct heritability, model likelihood, direct genetic variance and EBV accuracy estimates were highest for RFI(C )and least for RFI(O )for both M1 and M2 models. A significant genetic correlation was also observed between RFI(O) and ADG, but not for RFI(C) and RFI(S). Including a season effect (M2) in the genetic evaluation of RFI(O) resulted in the smallest heritability, model LogL, EBV accuracy and largest residual variance estimates. These results, though not conclusive, suggest a possible effect of seasonality on feed intake and thus feed efficiency.

This 3-yr study used 490 steers to determine whether feedlot steers changed their feed efficiency (FE) ranking when fed a grower diet then a finisher diet. The steers were crossbreds and were between 5 to 7 mo of age. There were two feeding periods each year. Within each year, approximately 90 steers had their diet switched from a grower to a finisher diet (feed-swap group), while another 90 steers were fed either the grower (grower-fed group) or the finisher (finisher-fed group) diet throughout the feeding trial. Each feeding test lasted for a minimum of 10 weeks and all steers were fed ad-libitum. Individual animal feed intakes were collected using the GrowSafe feeding system and body weights were measured every 2 weeks. Residual feed intake (RFI), gain to feed ratio (G:F) and Kleiber ratio (KR) were computed at the end of each feeding period. For each measure of efficiency, animals were classified as low, medium or high based on 0.5 SD from the mean. Majority of steers did not maintain the previous efficiency class in the second period. Approximately 58%, 51% and 51% of steers in the feed-swap group, finisher-fed group and the grower-fed group, respectively, changed their RFI measure by 0.5 SD. A Low rank correlation occurred in all test groups but was lower in the feed-swap group. Spearman rank correlations between the two feeding periods in the feed-swap group were 0.33, 0.20 and 0.31 for RFI, G:F and KR, respectively. Classifications based on G:F and KR showed that a greater number of steers (P < 0.05) in the feed-swap group did not maintain their feed efficiency class from one feeding regime to the other, while classification based on RFI did not show any difference (P > 0.05) between the proportions of individuals that changed or maintained their feed efficiency class. In the groups without a feed-swap, there was no difference (P > 0.05) in the proportion of steers that changed or maintained the same feed efficiency class for all FE measures. Our results suggest that diet type and feeding period affect the FE ranking in beef steers. A feedlot diet is ideal for evaluating the feed efficiency potential of steers for feedlot profitability; however we suggest that tests involving less dense diets should be examined in an effort to understand the relationships between feed efficiency and feeder profitability.