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The effects of nitrogen and straw management on global warming potential (GWP) and greenhouse gas intensity (GHGI) in a winter wheat–summer maize double-cropping system on the North China Plain were investigated. We measured nitrous oxide (N2O) emissions and studied net GWP (NGWP) and GHGI by calculating the net exchange of CO2 equivalent (CO2-eq) from greenhouse gas emissions, agricultural inputs and management practices, as well as changes in soil organic carbon (SOC), based on a long-term field experiment established in 2006. The field experiment includes six treatments with three fertilizer N levels (zero N (control), optimum and conventional N) and straw removal (i.e. N0, Nopt and Ncon) or return (i.e. SN0, SNopt and SNcon). Optimum N management (Nopt, SNopt) saved roughly half of the fertilizer N compared to conventional agricultural practice (Ncon, SNcon), with no significant effect on grain yields. Annual mean N2O emissions reached 3.90 kg N2O-N ha−1 in Ncon and SNcon, and N2O emissions were reduced by 46.9% by optimizing N management of Nopt and SNopt. Straw return increased annual mean N2O emissions by 27.9%. Annual SOC sequestration was 0.40–1.44 Mg C ha−1 yr−1 in plots with N application and/or straw return. Compared to the conventional N treatments the optimum N treatments reduced NGWP by 51%, comprising 25% from decreasing N2O emissions and 75% from reducing N fertilizer application rates. Straw return treatments reduced NGWP by 30% compared to no straw return because the GWP from increments of SOC offset the GWP from higher emissions of N2O, N fertilizer and fuel after straw return. The GHGI trends from the different nitrogen and straw management practices were similar to the NGWP. In conclusion, optimum N and straw return significantly reduced NGWP and GHGI and concomitantly achieved relatively high grain yields in this important winter wheat–summer maize double-cropping system.

Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 ( CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype ( P  < 0.01) or CYP2C19 *2/*3 genotype ( P  < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 ( P  < 0.01) or 2 ( P  < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.

Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P<0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P<0.05). The white blood cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased significantly in heat-stressed pigs (P<0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P<0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.

Introduction/BackgroundWe seek to find the significance of serum squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting tumor recurrence and survival in cervical squamous cell carcinoma receiving radical surgery.MethodologyA total of 3471 patients with stages IB1 to IIA2 cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The cut-off value of serum SCC-Ag for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The progression-free survival (PFS) and overall survival (OS) were assessed to estimate the significance of SCC-Ag.ResultsThe optimal cut-off value of serum SCC-Ag level for predicting tumor recurrence was calculated and set at 2.75ng/mL. Compared with 1.5 ng/mL used in clinical practice, serum SCC-Ag level >2.75 ng/mL was closely related to extrapelvic metastatic disease when patients relapse (P=0.035). Multivariate analysis showed that serum SCC-Ag level >1.5 ng/mL and serum SCC-Ag level >2.75 ng/mL were neither independent risk factors for PFS nor OS in all the patients. But in 964 patients with one or more high-risk factors (parametrial invasion, vaginal margin invasion and lymph node metastasis), instead of serum SCC-Ag level >1.5 ng/mL, serum SCC-Ag level >2.75 ng/mL could be used as an independent factor affecting PFS (P=0.018, HR=1.538).ConclusionPreoperative serum SCC-Ag level >2.75 ng/mL is closely related to extrapelvic recurrence, and is an independent factor for tumor recurrence and survival in cervical squamous cell carcinoma patients with high-risk factors.DisclosureNothing to disclose.

Helicobacter pylori infection induces chronic inflammation that contributes to gastric tumorigenesis. Tumor necrosis factor (TNF-α) is a proinflammatory cytokine, and polymorphism in the TNF-α gene increases the risk of gastric cancer. We herein investigated the role of TNF-α in gastric tumorigenesis using Gan mouse model, which recapitulates human gastric cancer development. We crossed Gan mice with TNF-α (Tnf) or TNF-α receptor TNFR1 (Tnfrsf1a) knockout mice to generate Tnf-/- Gan and Tnfrsf1a-/- Gan mice, respectively, and examined their tumor phenotypes. Notably, both Tnf-/- Gan mice and Tnfrsf1a-/- Gan mice showed similar, significant suppression of gastric tumor growth compared with control Tnf+/+ or Tnfrsf1a+/+ Gan mice. These results indicate that TNF-α signaling through TNFR1 is important for gastric tumor development. Bone marrow (BM) transplantation experiments showed that TNF-α expressed by BM-derived cells (BMDCs) stimulates the TNFR1 on BMDCs by an autocrine or paracrine manner, which is important for gastric tumor promotion. Moreover, the microarray analysis and colony formation assay indicated that NADPH oxidase organizer 1 (Noxo1) and Gna14 are induced in tumor epithelial cells in a TNF-α-dependent manner, and have an important role in tumorigenicity and tumor-initiating cell property of gastric cancer cells. Accordingly, it is possible that the activation of TNF-α/TNFR1 signaling in the tumor microenvironment promotes gastric tumor development through induction of Noxo1 and Gna14, which contribute to maintaining the tumor cells in an undifferentiated state. The present results indicate that targeting the TNF-α/TNFR1 pathway may be an effective preventive or therapeutic strategy for gastric cancer.

Introduction/BackgroundThe purpose of our study was to presentgenetic susceptibility and treatment related gene profiling in Chinese ovarian cancer patients.MethodologyWe have applied next-generation sequencing in consecutive patients who underwent primary surgery for ovarian cancer since 2016 at our institution. 241 patients have been enrolled for blood tests so far. Paired tumor samples from 62 patients have been tested for somatic deleterious mutations.ResultsThe median (range) age of patients was 54 (35–83) years old. 27.4% (66/241) patients had germline deleterious mutations. The most frequently reported genes were as follows: 29 (12.8%) BRCA1 mutations, 19 (7.9%) BRCA2 mutations, 6 (2.5%) RAD51C mutations, and 6 (2.5%) RAD51D mutations. Other mutated genes investigated included BRIP1 (2), CHEK2 (2), RAD50 (2), MRE11A (2), PMS1 (1) and MLH1 (1). 4 patients had dual gene mutation, that is BRCA1/PMS1, BRCA1/RAD50, BRCA2/BRIP1, and BRCA2/RAD51D. For the paired tumor samples, 19 (30.6%) deleterious TP53 mutations were identified, 4 patients had somatic BRCA1 mutations and 1 patient had somatic BRCA2 mutation.ConclusionOur results suggest a comprehensive profiling for Chinese ovarian cancer patients. Somatic genetic test could help better stratify patients for individualized treatment.DisclosureNothing to disclose.

Helicobacter pylori infection induces chronic inflammation that contributes to gastric tumorigenesis. Tumor necrosis factor (TNF-α) is a proinflammatory cytokine, and polymorphism in the TNF-α gene increases the risk of gastric cancer. We herein investigated the role of TNF-α in gastric tumorigenesis using Gan mouse model, which recapitulates human gastric cancer development. We crossed Gan mice with TNF-α ( Tnf ) or TNF-α receptor TNFR1 ( Tnfrsf1a ) knockout mice to generate Tnf −/− Gan and Tnfrsf1a −/− Gan mice, respectively, and examined their tumor phenotypes. Notably, both Tnf −/− Gan mice and Tnfrsf1a −/− Gan mice showed similar, significant suppression of gastric tumor growth compared with control Tnf +/+ or Tnfrsf1a +/+ Gan mice. These results indicate that TNF-α signaling through TNFR1 is important for gastric tumor development. Bone marrow (BM) transplantation experiments showed that TNF-α expressed by BM-derived cells (BMDCs) stimulates the TNFR1 on BMDCs by an autocrine or paracrine manner, which is important for gastric tumor promotion. Moreover, the microarray analysis and colony formation assay indicated that NADPH oxidase organizer 1 ( Noxo1) and Gna14 are induced in tumor epithelial cells in a TNF-α-dependent manner, and have an important role in tumorigenicity and tumor-initiating cell property of gastric cancer cells. Accordingly, it is possible that the activation of TNF-α/TNFR1 signaling in the tumor microenvironment promotes gastric tumor development through induction of Noxo1 and Gna14 , which contribute to maintaining the tumor cells in an undifferentiated state. The present results indicate that targeting the TNF-α/TNFR1 pathway may be an effective preventive or therapeutic strategy for gastric cancer.

PurposeThe South Australian Aboriginal Birth Cohort (SAABC) is a prospective, longitudinal birth cohort established to: (1) estimate Aboriginal child dental disease compared with population estimates; (2) determine the efficacy of an early childhood caries intervention in early versus late infancy; (3) examine if efficacy was sustained over time and; (4) document factors influencing social, behavioural, cognitive, anthropometric, dietary and educational attainment over time.ParticipantsThe original SAABC comprised 449 women pregnant with an Aboriginal child recruited February 2011 to May 2012. At child age 2 years, 324 (74%) participants were retained, at age 3 years, 324 (74%) participants were retained and at age 5 years, 299 (69%) participants were retained. Fieldwork for follow-up at age 7 years is underway, with funding available for follow-up at age 9 years.Findings to dateAt baseline, 53% of mothers were aged 14–24 years and 72% had high school or less educational attainment. At age 3 years, dental disease experience was higher among children exposed to the intervention later rather than earlier in infancy. The effect was sustained at age 5 years, but rates were still higher than general child population estimates. Experiences of racism were high among mothers, with impacts on both tooth brushing and toothache. Compared with population estimates, levels of self-efficacy and self-rated oral health of mothers at baseline were low.Future plansOur data have contributed to a better understanding of the environmental, behavioural, dietary, biological and psychosocial factors contributing to Aboriginal child oral and general health, and social and emotional well-being. This is beneficial in charting the trajectory of cohort participants’ health and well-being overtime, particularly in identifying antecedents of chronic diseases which are highly prevalent among Aboriginal Australians. Funding for continued follow-up of the cohort will be sought.Trial registration numberACTRN12611000111976; Post-results.

China has a vast area of saline-alkali land, and cultivating salt-tolerant plant varieties is crucial for improving the saline-alkali environment. Tulips are known to have a certain level of salt tolerance. This study aimed to investigate the physiological responses of different tulip cultivars to salt stress during bulb germination. Four conventional tulip cultivars: ‘Candy Apple Delight’, ‘Orange Emperor’, ‘Salmon Impression’ and ‘Red Impression’, were chosen as research materials. After bulb germinating, we were subjected to salt stress using 0.4 mol L –1 NaCl solution. Phenotypic observations of roots and leaves were conducted on the 0, 3, 6, 9, 12, 15, 18, and 21 days of treatment. The roots of the treatment group and the control group were collected to analyze peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), Na + /K + -ATPase activities, and hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA), and proline (Pro) levels. The results show: (1) Salt stress had the most severe effect on the aboveground part of ‘Orange Emperor’, the greatest impact on the underground part of ‘Candy Apple Delight’, and the least impact on ‘Salmon Impression’ and ‘Red Impression’; (2) under salt stress, the POD activity of tulip cultivars showed a consistent variation trend. Both ‘Candy Apple Delight’ and ‘Salmon Impression’ exhibited an initial increase followed by a decrease in SOD, CAT activities, and MDA content. On the other hand, the trend for H 2 O 2 , Pro, and Na + /K + -ATPase activity was ‘decreasing—increasing—decreasing’. The H 2 O 2 , MDA, Pro, and Na + /K + -ATPase activities of ‘Orange Emperor’ were in line with the variation trends of H 2 O 2 and MDA in ‘Red Impression’, which also followed a ‘decreasing—increasing—decreasing’ pattern. The SOD and CAT activity of ‘Orange Emperor’ and ‘Red Impression’, as well as Pro and Na + /K + -ATPase Activity with ‘Red Impression’, showed a similar changing trend of initial increase followed by a decrease. However, the response time to salt stress varied among different cultivars and indexes. (3) Principal component analysis revealed that the salt tolerance of the four tulip cultivars was ranked as ‘Red Impression’ > ‘Salmon Impression’ > ‘Candy Apple Delight’ > ‘Orange Emperor’, and the 6th of salt stress was the most sensitive period of tulip cultivars to salt stress. In conclusion, all tulip cultivars have a certain level of adaptability to salt stress, but there are variations among the different cultivars. The ability to adapt to salt stress can be enhanced through the coordination of various physiological indicators. This study elucidated the physiological mechanism of salt tolerance in different tulip cultivars, providing valuable insights for tulip cultivation in saline-alkali soil and contributing to further scientific research on tulips.

Introduction/BackgroundThe aim of our study was to investigate whether metastatic patterns were associated with prognosis in patients with FIGO stage IV high-grade serous ovarian cancer (HGSC).MethodologyWe retrospectively investigated FIGO stage IV HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. Metastatic patterns were defined as pleural effusion (stage IVA), parenchymal metastases (stage IVB), and extra-abdominal lymph node metastases (stage IVB). Clinical characters and metastatic patterns were compared with chi-squared or Fisher’s exact tests as appropriate. Overall survival was analyzed using Kaplan-Meier method and Cox proportional hazards model.ResultsA total of 83 consecutive stage IV HGSC patients were identified. 42 (50.6%) patients were sub-classified into stage IVA with pleural effusion. Among the rest stage IVB patients, 19 (22.9%) patients had parenchymal metastases and 22 (26.5%) had extra-abdominal lymph node metastases. Five-year overall survival of stage IVA and IVB patients was 39.7% and 39.4%, respectively (p=0.711). Besides, there were no survival differences among three metastatic patterns (p=0.701).ConclusionOur study demonstrated that neither the sub-classification into FIGO IVA and IVB nor metastatic patterns of FIGO stage IV provided additional prognostic information.DisclosureNothing to disclose.