Growth and yield of maize in response to reduced fertilizer application and its impacts on population dynamics and community biodiversity of insects and soil microbes.

In the North China Plain, farmers are using excessive amounts of fertilizer for the production of high-yield crop yield, which indirectly causes pollution in agricultural production. To investigate an optimal rate of fertilizer application for summer maize, the fertilizer reduction experiments with 600 kg/ha NPK (N: P2O5: K2O = 28: 8: 10) as normal fertilizer application (NFA), (i.e., 100F), were conducted successively during 2020 and 2021 to study the effects of reduced fertilizer rates, including 90% (540 kg/ha; i.e., 90F), 80% (480 kg/ha; i.e., 80F), 62.5% (375 kg/ha; i.e., 62.5F) and 50% (300 kg/ha; i.e., 50F) of NFA, on the plant growth of maize, the dynamics of key population abundances and community diversity of insects, and the composition and diversity of microbial community and finally to find out the N-metabolic enzymes' activity in soil. Our findings revealed that the fertilizer reduction rates by 10% - 20% compared to the current 100% NFA, and it has not significantly affected the plant growth of maize, not only plant growth indexes but also foliar contents of nutrients, secondary metabolites, and N-metabolic enzymes' activity. Further, there was no significant alteration of the key population dynamics of the Asian corn borer (Ostrinia furnacalis) and the community diversity of insects on maize plants. It is interesting to note that the level of N-metabolic enzymes' activity and microbial community diversity in soil were also not affected. While the fertilizer reduction rate by 50% unequivocally reduced field corn yield compared to 100% NFA, significantly decreased the yield by 17.10%. The optimal fertilizer application was calculated as 547 kg/ha (i.e., 91.17% NFA) based on the simulation analysis of maize yields among the five fertilizer application treatments, and the fertilizer application reduced down to 486 kg/ha (i.e., 81.00% NFA) with a significant reduction of maize yield. These results indicated that reduced the fertilizer application by 8.83% - 19.00% is safe and feasible to mitigate pollution and promote sustainable production of maize crops in the region.

Development of a prognostic model for personalized prediction of colon adenocarcinoma (COAD) patient outcomes using methylation-driven genes.

The objective of this study was to identify methylation-driven genes and explore their prognostic value in colon adenocarcinoma (COAD). The Cancer Genome Atlas (TCGA) database was used to acquire collated COAD transcriptome gene expression matrix (containing 59,427 transcripts), transcriptome gene methylation level matrix (containing 29,602 methylated modified genes), which included 517 samples containing 41 samples of normal tissue (NT) & 476 samples of COAD, and patient clinical information files (including patient survival time, survival status, age, gender and tumor stage, etc.), for all COAD samples. A total of 9807 differentially expressed genes (DEGs) were obtained by DEG analysis of the COAD transcriptional expression matrix, of which 5874 were up-regulated and 3933 were down-regulated. And 46 methylation-driven DEGs (MD-DEGs) in COAD were obtained by DEG analysis, differential analysis of gene methylation levels, and correlation analysis between them. Next, three prognostic associated MD-DEGs (PMD-DEGs) (IDUA, ZBTB18 and C5orf38) were identified by Cox regression analysis, and a prognostic model composed of the three PMD-DEGs was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis and cross-validation analysis. In addition, survival analysis, the receiver operating characteristics (ROC) curve analysis and independent prognostic analysis were used to evaluate and verify that the prognostic model we constructed could accurately and independently predict the prognosis of COAD patients. Finally, we constructed a nomogram based on the prognosis model to accurately and personalized predict the survival prognosis of COAD patients. In conclusion, we identified the methylation driver gene of COAD and constructed a prognostic model and nomogram to personalized predict the prognosis of patients, which opened a new prospect for accurate diagnosis and treatment in clinical practice.

Effective Removal of Fe (III) from Strongly Acidic Wastewater by Pyridine-Modified Chitosan: Synthesis, Efficiency, and Mechanism.

A novel pyridine-modified chitosan (PYCS) adsorbent was prepared in a multistep procedure including the successive grafting of 2-(chloromethyl) pyridine hydrochloride and crosslinking with glutaraldehyde. Then, the as-prepared materials were used as adsorbents for the removal of metal ions from acidic wastewater. Batch adsorption experiments were carried out to study the impact of various factors such as solution pH value, contact time, temperature, and Fe (III) concentration. The results showed that the absorbent exhibited a high capacity of Fe (III) and the maximum adsorption capacity was up to 66.20 mg/g under optimal experimental conditions (the adsorption time = 12 h, pH = 2.5, and T = 303 K). Adsorption kinetics and isotherm data were accurately described by the pseudo-second-order kinetic model and Sips model, respectively. Thermodynamic studies confirmed that the adsorption was a spontaneous endothermic process. Moreover, the adsorption mechanism was investigated using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results revealed the pyridine group forms a stable chelate with iron (III) ions. Therefore, this acid-resistant adsorbent exhibited excellent adsorption performance for heavy metal ions from acidic wastewater compared to the conventional adsorbents, helping realize direct decontamination and secondary utilization.

Transient Liquid Phase Diffusion Bonding of Ni3Al Superalloy with Low-Boron Nickel-Base Powder Interlayer.

As a technology for micro-deformed solid-phase connection, transient liquid phase (TLP) diffusion bonding plays a key role in the manufacture of heating components of aero engines. However, the harmful brittle phase and high hardness limit the application of TLP diffusion bonding in nickel-based superalloys. In this paper, a new strategy in which a low-boron and high-titanium interlayer can restrain the brittle phase and reduce the hardness of the TLP-diffusion-bonded joint is proposed. With this strategy, the Ni3Al joint can achieve a high strength of 860.84 ± 26.9 MPa under conditions of 1250 °C, 6 h and 5 MPa. The microhardness results show that the average microhardness of the joint area is 420.33 ± 3.15 HV and is only 4.3% higher than that of the Ni3Al base material, which proves that this strategy can effectively inhibit the formation of the harmful brittle phase in the joint area. The results of EBSD show that 7.7% of the twin boundaries exist in the isothermal solidification zone, and only small amounts of secondary precipitates are observed at the grain boundaries in the joint, which indicates that twin boundaries may play a dominant role in crack initiation. This study provides a feasible avenue to suppress the brittle phase in TLP-diffusion-bonded joints.

H2O2 modified peanut shell-derived biochar/alginate composite beads as a green adsorbent for removal of Cu(II) from aqueous solution.

In this study, a novel composite bead (MPB-ALG) was prepared by encapsulating H2O2 modified peanut shell-derived biochar (MPB) into alginate matrix through a facile method. The structure and properties of prepared materials were characterized using FTIR, BET, SEM, and XPS. Batch adsorption experiments were performed to compare the Cu(II) adsorption performance of MPB, plain alginate beads (ALG), and MPB-ALG. The effect parameters of the components, solution pH, contact time, initial concentration, and coexisting ions were studied systematically. The results showed that the maximum adsorption capacity of the optimized MPB-ALG-1 (MPB/alginate = 1:1 w/w%) was 117.4 mg g-1 at pH 5, which was much higher than that of MPB (37.4 mg g-1). The adsorption kinetics and isotherms data of Cu(II) on MPB-ALG-1 were well described by Elovich kinetic model and Freundlich adsorption isotherm. Compared with plain ALG beads, MPB-ALG-1 exhibited better reusability and anti-interference of coexisting ions. Finally, the adsorption mechanisms of Cu(II) on MPB-ALG-1 beads were revealed by FTIR and XPS analysis. The experimental results demonstrated that MPB-ALG-1 beads can be used as an environmentally friendly and efficient adsorbent for the removal of Cu(II) from wastewater.

Adsorption Performance of Methylene Blue by KOH/FeCl3 Modified Biochar/Alginate Composite Beads Derived from Agricultural Waste.

In this study, high-performance modified biochar/alginate composite bead (MCB/ALG) adsorbents were prepared from recycled agricultural waste corncobs by a high-temperature pyrolysis and KOH/FeCl3 activation process. The prepared MCB/ALG beads were tested for the adsorption of methylene blue (MB) dye from wastewater. A variety of analytical methods, such as SEM, BET, FTIR and XRD, were used to investigate the structure and properties of the as-prepared adsorbents. The effects of solution pH, time, initial MB concentration and adsorption temperature on the adsorption performance of MCB/ALG beads were discussed in detail. The results showed that the adsorption equilibrium of MB dye was consistent with the Langmuir isothermal model and the pseudo-second-order kinetic model. The maximum adsorption capacity of MCB/ALG-1 could reach 1373.49 mg/g at 303 K. The thermodynamic studies implied endothermic and spontaneous properties of the adsorption system. This high adsorption performance of MCB/ALG was mainly attributed to pore filling, hydrogen bonding and electrostatic interactions. The regeneration experiments showed that the removal rate of MB could still reach 85% even after five cycles of experiments, indicating that MCB/ALG had good reusability and stability. These results suggested that a win-win strategy of applying agricultural waste to water remediation was feasible.

Impacts of corn intercropping with soybean, peanut and millet through different planting patterns on population dynamics and community diversity of insects under fertilizer reduction.

Corn is one of the key grain crops in China and the excessive use of chemical fertilizers and pesticides seriously damages the ecological environment in fields. To explore a more scientific and reasonable way to plant corn and simultaneously reduce the overuse of chemical fertilizers and pesticides, the impact of corn intercropping with soybean, peanut, and millet, respectively, through five planting patterns, including three intercropping patterns (2 corn rows to 2, 3 and 4 rows of soybean/peanut or 2, 4 and 6 millet rows, respectively) and two monoculture patterns of corn and soybean, peanut or millet under normal (600 kg/ha) and reduced (375 kg/ha) levels of NPK (N:P2O5:K2O = 15:15:15) fertilization on the population abundance and community diversity of insects, leaf nutrients, and induced plant hormones jasmonic acid (JA) and salicylic acid (SA) was studied in 2018 and 2019. The results showed that the insect community indexes of the species number (S), the diversity index (H), and the uniformity index (E) generally increased under intercropping and were significantly higher than those under corn monoculture. The prevalence of Asian corn borer (Ostrinia furnacalis) on the intercropping corn plants decreased by based on the average of seven surveys per year for each treatment 2.9 to 17 heads per 30 plants compared with that on the monoculture corn plants. The number of natural enemy insect species on corn plants under intercropping was significantly higher than that under corn monoculture. That is, intercropping may decrease the population of Asian corn borers by increasing S, H, E, and natural enemy insect species (NEI). Moreover, intercropping type and fertilizer level significantly affected corn leaf nutrient contents. Compared with the normal fertilizer level, fertilizer reduction significantly reduced the foliar contents of amino acids, soluble protein, and soluble sugar in corn plants. In addition, corn-soybean and corn-peanut intercropping significantly increased the three nutrient contents in corn leaves compared with corn monoculture. In terms of corn nutrients, intercropping could compensate for the effects of fertilizer reduction. The foliar content of JA in corn-soybean intercropping was significantly higher than in corn monoculture. Under corn-soybean and corn-peanut intercropping, SA was significantly lower than under corn monoculture. Overall, intercropping, not fertilizer reduction, can significantly increase insect community diversity while reducing the population abundances of the key insect pest species on corn plants. Intercropping reduced the SA content, increased amino acids and thus reduced the susceptibility of corn to the pest insects.

Investigation of the Tribological Behavior and Microstructure of Plasma-Cladded Fe-Cr-Mo-Ni-B Coating.

In this study, an Fe-Cr-Mo-Ni-B coating was prepared using plasma cladding on Cr5 steel substrate. The microstructure, phase evolution and tribological performance of the Fe-Cr-Mo-Ni-B coating were investigated. The microstructure is mainly composed of Mo2FeB2, Fe2B, α-Fe, γ-Fe and MoB. The process of phase evolution in the coating was observed in situ by HT-CLSM. The Mo2FeB2 phase with good thermodynamic stability can exist in the high-temperature liquid phase. It also has a phenomenon of connection and merging and turns into different morphology during the plasma cladding process. The hardness value of coating was much higher than the base metal, and the hardness value of Mo2FeB2 (785.5 HV) was higher than the eutectic matrix (693.2 HV). The wear mechanisms of the cladding under dry sliding were primarily caused by adhesive wear, accompanying slight oxidation wear. The Mo2FeB2 phase has an important effect on the wear resistance property.

Visible-light-driven photocatalytic N2 fixation to nitrates by 2D/2D ultrathin BiVO4 nanosheet/rGO nanocomposites.

Photocatalytic nitrogen fixation is a promising approach owing to its environmental friendliness and cost-effectiveness. The 2D/2D BiVO4/rGO hybrid developed in this study exhibits a high nitrate-production rate of 1.45 mg h-1 g-1 and an apparent quantum efficiency (QE) of 0.64% at 420 nm, which represents one of the most highly active photocatalysts reported thus far.

[Transurethral columnar balloon dilation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To study the clinical effect of transurethral columnar balloon dilation of the prostate (TUCBDP) in the treatment of BPH and introduce the experience with the surgical procedure. METHODS: We retrospectively analyzed the clinical data on 265 cases of BPH treated by TUCBDP from August 2016 to August 2019. RESULTS: Operations were successfully completed in all the cases, with the mean operation time of (24.67 ± 7.6) min and the average intraoperative blood loss of (26.5 ± 21.4) ml, and all the patients had urinary patency after removal of the catheter. Follow-up examinations every 3 months after surgery showed significant improvement over the baseline in IPSS, quality of life score (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR) and other indicators (P < 0.05). Forty-five of the patients with sexual life exhibited no significant difference from the baseline in IIEF-5 and erectile hardness scale (EHS) scores (P > 0.05). Postoperative complications were observed in 53 cases (20%), including 28 cases of transient urinary incontinence (10.56%), 3 cases of hemorrhage (1.13%), 11 cases of urinary tract infection (4.15%), 1 case of urethral stricture (0.37%), and 8 cases of acute urinary retention (3.01%), which were all improved after regular treatment, with no occurrence of true urinary incontinence. Retrograde ejaculation occurred in 2 (4.45%) of the 45 patients with sexual life. CONCLUSIONS: Transurethral columnar balloon dilation of the prostate, with the advantages of short operation time and less intraoperative bleeding, has a significant short-term clinical effect in the treatment of BPH, particularly suitable for the elderly and those who want to retain the sexual function. Intraoperative localization of the protrusion may significantly influence the outcome of surgery, which deserves strengthened studies. Special attention should be paid to the incidence of postoperative transient urinary incontinence.

AMF Inoculation Can Enhance Yield of Transgenic Bt Maize and Its Control Efficiency Against Mythimna separata Especially Under Elevated CO2.

The promotion and application of transgenic Bt crops provides an approach for the prevention and control of target lepidopteran pests and effectively relieves the environmental pressure caused by the massive usage of chemical pesticides in fields. However, studies have shown that Bt crops will face a new risk due to a decrease in exogenous toxin content under elevated carbon dioxide (CO2) concentration, thus negatively affecting the ecological sustainability of Bt crops. Arbuscular mycorrhizal fungi (AMF) are important beneficial microorganisms that can effectively improve the nutrient status of host plants and are expected to relieve the ecological risk of Bt crops under increasing CO2 due to global climate change. In this study, the Bt maize and its parental line of non-transgenic Bt maize were selected and inoculated with a species of AMF (Funneliformis caledonium, synonyms: Glomus caledonium), in order to study the secondary defensive chemicals and yield of maize, and to explore the effects of F. caledonium inoculation on the growth, development, and reproduction of the pest Mythimna separata fed on Bt maize and non-Bt maize under ambient carbon dioxide concentration (aCO2) and elevated carbon dioxide concentration (eCO2). The results showed that eCO2 increased the AM fungal colonization, maize yield, and foliar contents of jasmonic acid (JA) and salicylic acid (SA), but decreased foliar Bt toxin content and Bt gene expression in Bt maize leaves. F. caledonium inoculation increased maize yield, foliar JA, SA contents, Bt toxin contents, and Bt gene expression in Bt maize leaves, and positively improved the growth, development, reproduction, and food utilization of the M. separata fed on non-Bt maize. However, F. caledonium inoculation was unfavorable for the fitness of M. separata fed on Bt maize, and the effect was intensified when combined with eCO2. It is indicated that F. caledonium inoculation had adverse effects on the production of non-Bt maize due to the high potential risk of population occurrence of M. separata, while it was just the opposite for Bt maize. Therefore, this study confirms that the AMF can increase the yield and promote the expression levels of its endogenous (JA, SA) and exogenous (Bt toxin) secondary defense substances of Bt maize under eCO2, and finally can enhance the insect resistance capacity of Bt crops, which will help ensure the sustainable utilization and safety of Bt crops under climate change.

[Inhibitory effect of 3-bromopyruvate on the proliferation, migration and invasive ability of prostate cancer PC-3 cells].

OBJECTIVE: To observe the effects of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the proliferation, migration and invasive ability of prostate cancer PC-3 cells in vitro and explore the underlying mechanisms. METHODS: We cultured prostate cancer PC-3 cells in vitro and treated them with 3-BrPA at different concentrations for 24, 48 and 72 hours. Then we observed the morphological changes of the PC-3 cells under the inverted microscope. We also detected the effects of different concentrations of 3-BrPA on the proliferation, migration and invasive ability of the cells by MTT, wound-scratch and Transwell assays and determined the protein expressions of glucose transporter-1 (GLUT1), matrix metalloproteinase-14 (MMP-14), MMP-9 and MMP-2 in the PC-3 cells by Western blot. RESULTS: More significant changes were observed in the morphology of the PC-3 cells with increased concentrations of 3-BrPA. MTT assay showed that the inhibition rate of the proliferation of the PC-3 cells was remarkably increased in a concentration- and time-dependent manner (P<0.01). Wound-scratch and Transwell assays exhibited significant decreases in the scratch healing rate and number of invasive cells after 24 hours of intervention with 3-BrPA at 25, 50 and 100 µmol/L, even more significant after treated for 48 hours at the concentrations of 50 and 100 µmol/L (P<0.01). The expressions of the GLUT1, MMP-14, MMP-9 and MMP-2 proteins were markedly down-regulated after 3-BrPA intervention in comparison with those in the control group (P<0.01). CONCLUSIONS: The glycolysis inhibitor 3-BrPA reduces the proliferation, migration and invasive ability of prostate cancer PC-3 cells by down-regulating the expressions of the related proteins GLUT1, MMP-14, MMP-9 and MMP-2.

Evaluating the effects of transgenic Bt rice cultivation on soil stability.

Insecticidal crystal (Cry) proteins produced by genetically modified rice that enter the soil via pollen dispersal, plant residues, and root exudation may disturb soil health. In the present study, we assessed the influences of transgenic Bt rice (i.e., HH1 with Cry1Ab/Cry1Ac) cultivation on the dynamics of soil carbon and nutrients under field conditions during 2013-2016. Transgenic treatments (transgenic Bt rice vs. its parental line (i.e., MH63) of non-Bt rice) have no consistently significant effects on soil property, including available nitrogen, available phosphorus, available potassium, total nitrogen, and total phosphorus, while apparent seasonal changes were observed. Besides, the variations of soil nutrients in the paddy field of transgenic Bt rice did not exceed their resistance capacities, except total organic carbon (TOC; RS (resistance) = 1.51) and total potassium (TK; RS = 2.62) in 2013 and TK (RS = 1.94) in 2014. However, the TOC and soil nutrient of TK in the paddy field of transgenic Bt rice have recovered to the pre-perturbation status after harvest (RL (resilience) = 1.01, F = 0.01, P = 0.91; RL = 0.98, F = 0.34, P = 0.58; RL = 0.99, F = 1.26, P = 0.29). Moreover, the paddy yield of transgenic Bt rice was consistently higher than that of its parental line of non-Bt rice. These results suggested that the cultivation of transgenic Bt rice has no adverse impact on soil stability in terms of soil carbon and nutrients and paddy yield.

Effects of elevated CO2 on foliar soluble nutrients and functional components of tea, and population dynamics of tea aphid, Toxoptera aurantii.

The rising atmospheric CO2 concentration has shown to affect plant physiology and chemistry by altering plant primary and secondary metabolisms. Nevertheless, the impacts of elevated CO2 on plant nutrients and functional components of tea remain largely unknown, which will likely affect tea quality and taste under climate change scenario. Being sources of nutrients and secondary chemicals/metabolites for herbivorous insects, the variation in foliar soluble nutrients and functional components of tea plants resulting from CO2 enrichment will further affect the herbivorous insects' occurrence and feeding ecology. In this study, the tea aphid, Toxoptera aurantii was selected as the phloem-feeding herbivore to study the effects of elevated CO2 on foliar soluble nutrients and functional components of tea seedlings, and the population dynamics of T. aurantii. The results indicated that elevated CO2 enhanced the photosynthetic ability and improved the plant growth of tea seedlings compared with ambient CO2, with significant increases in net photosynthetic rate (+20%), intercellular CO2 concentration (+15.74%), leaf biomass (+15.04%) and root-to-shoot ratio (+8.08%), and significant decreases in stomatal conductance (-5.52%) and transpiration rate (-9.40%) of tea seedlings. Moreover, elevated CO2 significantly increased the foliar content of soluble sugars (+4.74%), theanine (+3.66%) and polyphenols (+12.01%) and reduced the foliar content of free amino acids (-9.09%) and caffeine (-3.38%) of tea seedlings compared with ambient CO2. Furthermore, the relative transcript levels of the genes of theanine synthetase (+18.64%), phenylalanine ammonia lyase (+49.50%), s'-adenosine methionine synthetase (+143.03%) and chalcone synthase (+61.86%) were up-regulated, and that of caffeine synthase (-56.91%) was down-regulated for the tea seedlings grown under elevated CO2 relative to ambient CO2. In addition, the foliar contents of jasmonic acid (+98.6%) and salicylic acid (+155.6%) also increased for the tea seedlings grown under elevated CO2 in contrast to ambient CO2. Also, significant increases in the population abundance of T. aurantii (+4.24%-41.17%) were observed when they fed on tea seedlings grown under elevated CO2 compared to ambient CO2. It is presumed that the tea quality and taste will be improved owing to the enhanced foliar soluble nutrients and functional components of tea seedlings under the climate change scenario, especially on account of the rising atmospheric CO2 concentration, while the climate change may exacerbate the occurrence of tea aphid, T. aurantii, despite the enhanced secondary defensive chemicals manifested by the CO2 enrichment.

PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer.

PURPOSE: In this study, we addressed the underlying mechanisms for the association between enzalutamide (ENZ) treatment and neuroendocrine prostate cancer (NEPC), and the critical involvement of MYCN, and loss of RB1 function in neuroendocrine differentiation (NED) of prostatic epithelial cells, and the development of NEPC. We further sought to determine whether PARP inhibition could suppress NEPC, and to identify molecular determinants of this therapeutic activity. EXPERIMENTAL DESIGN: We used a novel prostate cancer patient-derived xenograft (PDX) treatment model, prostatic adenocarcinoma and NEPC cell lines, an NEPC organoid line, and NEPC xenograft models to address the mechanistic basis of ENZ-induced NED, and to analyze suppression of NED and NEPC growth by PARP inhibition. RESULTS: We identified an ENZ treatment-associated glucocorticoid receptor (GR)-MYCN-CDK5-RB1-E2F1 signaling pathway that drives NED in prostatic adenocarcinoma PDX and cell line models. Mechanistically, long-term ENZ treatment transcriptionally upregulates signaling of the GR-MYCN axis, leading to CDK5R1 and CDK5R2 upregulation, Rb1 phosphorylation, and N-Myc-mediated and E2F1-mediated NED gene expression. Importantly, olaparib (OLA) or talazoparib (TALA) suppressed these activities, and the combination of OLA and dinaciclib (DINA), an inhibitor of CDK2 and CDK5, which also inhibits Rb1 phosphorylation, suppressed NED and significantly improved therapeutic efficiency in NEPC cells in vitro and in NEPC tumors in vivo. CONCLUSIONS: The results of our study indicate an important role of GR-MYCN-CDK5R1/2-RB1-NED signaling in ENZ-induced and PARP inhibitor-suppressed NEPC. We also demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models.

Effects of seed mixture sowing with transgenic Bt rice and its parental line on the population dynamics of target stemborers and leafrollers, and non-target planthoppers.

The widespread planting of insect-resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impacts on both target and non-target pests. In this study, we examined the potential effects of intra-specific seed mixture sowing with transgenic Bt rice (Bt) and its parental non-transgenic line (Nt) (100% Bt rice [Bt100 ], 5% Nt+95% Bt [Nt05 Bt95 ], 10% Nt+90% Bt [Nt10 Bt90 ], 20% Nt+80% Bt [Nt20 Bt80 ], 40% Nt+60% Bt [Nt40 Bt60 ] and 100% Nt rice [Nt100 ]) on target and non-target pests in a 2-year field trial in southern China. The occurrence of target pests, Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis, decreased with the increased ratio of Bt rice, and the mixture ratios with more than 90% Bt rice (Bt100 and Nt05 Bt95 ) significantly increased the pest suppression efficiency, with the lowest occurrences of non-target planthoppers, Nilaparvata lugens and Sogatella furcifera in Nt100 and Nt05 Bt95 . Furthermore, there were no significant differences in 1000-grain dry weight and grain dry weight per 100 plants between Bt100 and Nt05 Bt95 . Seed mixture sowing of Bt rice with ≤10% (especially 5%) of its parent line was sufficient to overcome potential compliance issues that exist with the use of block or structured refuge to provide most effective control of both target and non-target pests without compromising the grain yield. It is also expected that the strategy of seed mixture sowing with transgenic Bt rice and the non-transgenic parental line would provide rice yield stability while decreasing the insecticide use frequency in rice production.

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration-resistant prostate cancer models.

Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4-2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub-G1) in VCaP and C4-2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p-EGFR (Y1068), p-AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133-4 patient-derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 µm2 ) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control-treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors.

Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer.

Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC).Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN-PARP-DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown in vitro and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models in vivoConclusions: Our results identify a novel MYCN-PARP-DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using in vitro and in vivo CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC-regulated DDR gene targets and the biological and clinical significance of MYCN-PARP-DDR signaling will more fully elucidate the importance of the MYCN-PARP-DDR signaling pathway in the development and maintenance of NEPC. Clin Cancer Res; 24(3); 696-707. ©2017 AACR.