A chromosome-level genome assembly of the beet armyworm Spodoptera exigua.

BACKGROUND: The beet armyworm Spodoptera exigua is a polyphagous caterpillar that causes serious damage to many species of crops and vegetables. To gain insight into how this polyphagous insect differs from less harmful oligophagous species, we generated a chromosome-level assembly and compared it to closely related species with the same or different feeding habits. RESULTS: Based on Illumina and Pacific Biosciences data and Hi-C technology, 425.6 Mb of genome sequences were anchored and oriented into 31 linkage groups, with an N50 length of 14.8 Mb. A total of 24,649 gene models were predicted, of which 97.4% were identified in the genome assembly. Chemosensory genes are vital for locating food: of the four main families, odorant-binding proteins, chemosensory proteins and olfactory receptors showed little difference, whereas gustatory receptors are greatly expanded in S. exigua. Examination of other polyphagous insects confirmed this difference from oligophagous congeners and further identified the bitter receptor subfamily as being particularly affected. CONCLUSION: Our high-quality genome sequence for beet armyworm identified a key expansion of the bitter gustatory receptor subfamily in this and other pests that differs crucially from more benign relatives and offers insight into the biology and possible future means of control for these economically important insects.

An Amphiphilic Surface with Improved Thermal Radiation for Water Harvesting.

Water scarcity poses a significant challenge for people living in arid areas. Despite the effectiveness of many bioinspired surfaces in promoting vapor condensation, their water-harvesting efficiency is insufficient. This is often exacerbated by overheating, which decreases the performance in terms of the micro-droplet concentration and movement on surfaces. In this study, we used a spotted amphiphilic surface to enhance the surfaces' water-harvesting efficiency while maintaining their heat emissivity. Through hydrophilic particle screening and hydrophobic groove modifying, the coalescence and sliding characteristics of droplets on the amphiphilic surfaces were improved. The incorporation of boron nitride (BN) nanoparticles further enhanced the surfaces' ability to harvest energy from condensation. To evaluate the water-harvesting performance of these amphiphilic surfaces, we utilized a real-time recording water-harvesting platform to identify microscopic weight changes on the surfaces. Our findings indicated that the inclusion of glass particles in hydrophobic grooves, combined with 1.0 wt.% BN nanoparticles, enhanced the water-harvesting efficiency of the amphiphilic surfaces by more than 20%.

The Expression of P35 Plays a Key Role in the Difference in Apoptosis Induced by AcMNPV Infection in Different Spodoptera exigua Cell Lines.

Baculovirus infection induces apoptosis in host cells, and apoptosis significantly affects virus production. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can regulate apoptosis, but the regulatory mechanism is unclear. Here, we found that AcMNPV infection induced different apoptosis responses in different Spodoptera exigua cell lines. In the early stages of viral infection (1-6 h), Se-1 cells underwent severe apoptosis, while Se-3 cells underwent very slight apoptosis. In the late stages of viral infection (12-72 h), Se-1 cells continued to undergo apoptosis and formed a large number of apoptotic bodies, while the apoptosis of Se-3 cells was inhibited and no apoptotic bodies were formed. To determine the reasons for the apoptosis differences in the two cell lines, we measured the expression of the six S. exigua cysteine-dependent aspartate specific protease genes (SeCaspase-1 to -6) and the three AcMNPV antiapoptotic protein genes (iap1, iap2 and p35) during viral infection. We found that SeCaspase-1 to -6 were all activated in Se-1 cells and inhibited in Se-3 cells, whereas iap1, iap2 and p35 were all inhibited in Se-1 cells and normally expressed in Se-3 cells. And p35 was expressed earlier than iap1 and iap2 in Se-3 cells. Otherwise, Se-1 and Se-3 cells would all be apoptotic when infected with the recombinant p35 knockout AcMNPV, whereas only Se-1 cells were apoptotic, but Se-3 cells were not apoptotic when infected with the recombinant p35 repair AcMNPV. Combined with the fact that the expression of P35 protein is inhibited in Se-1 cells but normally expressed in Se-3 cells during the infection of recombinant p35 repair AcMNPV, we proposed that the different expression of P35 is an important reason for the apoptosis differences between the two cell lines. We also found that some genes associated with apoptosis can probably regulate the expression of P35. However, the major upstream regulators of P35 and their mechanisms are still unclear and will be studied in the future.

Extensive secretion of phenolic acids and fatty acids facilitates rhizosphere pH regulation in halophyte Puccinellia tenuiflora under alkali stress.

Puccinellia tenuiflora is a forage grass with high nutritional value that is an extreme alkali-tolerant halophyte: it can survive at pH 10-11. Root secretion is perceived as a major plant alkali tolerance mechanism. In the present study, we applied a widely targeted metabolomic approach to identify and quantify the root exudates of P. tenuiflora under alkali stress. We also surveyed the transcriptional and metabolic profiling of P. tenuiflora roots under salt (96-mM Na+ , pH 6.8) and alkali (96-mM Na+ , pH 9.6) stresses to reveal the biological processes mediating root secretion. In P. tenuiflora plants, 493 root exudates were detected under control conditions, 544 root exudates under salt stress conditions, and 607 root exudates under alkali stress conditions. Salt-stressed plants and alkali-stressed plants shared 64 root exudates, and 60 root exudates were unique to alkali-stressed plants. The secretion rate of 56 phenolic acids, 43 fatty acids, and 9 organic acids was faster in alkali-stressed roots than in control and salt-stressed roots. In P. tenuiflora roots, alkali stress enhanced the accumulation of 23 phenolic acids, five organic acids, and only one fatty acid. In addition, transcriptomic analysis revealed that alkali stress upregulated glycolysis and phenylpropanoid biosynthesis pathways in P. tenuiflora roots. Taken together, extensive secretion of phenolic acids and fatty acids promotes rhizosphere pH regulation of P. tenuiflora under alkali stress, which contributes to its strong alkali tolerance. The root secretion of P. tenuiflora upon alkali stress is highly organized. Enhanced glycolysis, phenylpropanoid biosynthesis, and organic acid synthesis in the roots provide more reducing power and carbon source for the root secretion process of alkali-stressed P. tenuiflora.

Dendritic Cells Therapy with Cytokine-Induced Killer Cells and Activated Cytotoxic T Cells Attenuated Th2 Bias Immune Response.

THE AIM OF THIS STUDY: The purpose of this study is to investigate whether the DC cells combined with CIK cells (DC/CIK) and DC activated cytotoxic T cells (DC-ACT) treatment can promote antitumor response and change the immune indicators by targeting the heterogeneous tumor cell populations at a system level. METHODS: In this study, 112 patients with cancer were assigned to the DC/CIK treatment and 116 patients received the DC-ACT therapy. We detected the lymphocyte subsets and other immune indicators pre- and post-treatment to evaluate the changes of patient's immunity and compare the differences in immune status between two adoptive cellular immunotherapies. RESULTS: DC/CIK therapy elevated the percentage of CD3+ HLA-DR+ T cells, NK cells and several serological cytokines such as IL-2, IL-6 after cell infusion (p < .05). DC-ACT therapy could increase the total CD3 + T cells, CD8 + T cells, CD3+ HLA-DR+ cells and IL-12 cytokines after cell infusion (p < .05). The levels of IL-4/IFN-γ, IL-4/IL-12 and IL-6/IL-12 were reduced significantly in the DC-ACT group compared with DC/CIK group. These observations suggested that DC-ACT therapy has more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile based on the immunomodulatory properties. CONCLUSIONS: These results indicated that DC, CIK, and DC-ACT cells exert anti-tumor activity through the different pathways. Thus, this work may provide valuable insights into the clinical curative effect evaluation of immunocyte therapy and the design of combined immunotherapeutic strategies for malignant tumors.

Toxicity and effects of four insecticides on Na+, K+-ATPase of western flower thrips, Frankliniella occidentalis.

Western flower thrips (WFT), Frankliniella occidentalis, has become an important pest of vegetables worldwide, due to its economic damage to crop production. In order to control WFT, chemical insecticides are widely used. However, WFT has developed a high resistance against many kinds of insecticides. Na+, K+-ATPase, playing an important role in the ionic transmission across the membrane, is commonly considered to be the target of several xenobiotic compounds. However, whether the Na+, K+-ATPase can be used as one of the target sites for controlling WFT is still unknown. In this study, resistance levels of WFT to four insecticides (chlorpyrifos, beta cypermethrin, abamectin, and thiamethoxam) were measured. It was found that all four insecticides exhibited significant inhibitory effects on WFT, especially on nymphs. The activity of Na+, K+-ATPase was estimated after the treatment of four insecticides. Additionally, mRNA expression levels of three Na+, K+-ATPase α-subunit isoforms (X1, X2 and X3) were detected using RT-qPCR. The transcription profile of three Na+, K+-ATPase α-subunit isoforms were diverse after treatment by these four insecticides, which indicated that these isoforms might play different roles in the tolerance to insecticides. The results suggested that Na+, K+-ATPase can obviously be inhibited by these four classes of insecticide, and may serve as the new target for controlling WFT.

Developing an Online Measurement Device Based on Resistance Sensor for Measurement of Single Grain Moisture Content in Drying Process.

The online measurement of moisture content for grains is an essential technology to realize real-time tracking and control, improve drying quality and reduce energy consumption of the drying process. To improve the measurement accuracy and reliability of the dynamic measurement process as well as expand the application scope of the device, the present work constructed an experimental equipment for determining dynamic resistance characteristics of a single grain. The relations between moisture content and real-time resistance waveform were revealed, and an analytical calculation method of peak value and peak area of waveform was proposed, which correctly revealed the electrical measurement properties of grain. The results demonstrated that the gap width between the electrodes had large influence on the sensor's performance. Moreover, an online measuring device was developed based on the experimental analysis and calculation method, and the test results in both lab and field for different grains showed that online real-time absolute measurement error are within ±0.5% in the varied moisture content (10-35%w.b.) and the temperature (-20-50 °C). The main results and the developed device might provide technical support for developing intelligent grain drying equipment.

Exergoeconomic Analysis of Corn Drying in a Novel Industrial Drying System.

The improvement of the design and operation of energy conversion systems is a theme of global concern. As an energy intensive operation, industrial agricultural product drying has also attracted significant attention in recent years. Taking a novel industrial corn drying system with drying capacity of 5.5 t/h as a study case, based on existing exergoeconomic and exergetic analysis methodology, the present work investigated the exergetic and economic performance of the drying system and identified its energy use deficiencies. The results showed that the average drying rate for corn drying in the system is 1.98 gwater/gdry matter h. The average exergy rate for dehydrating the moisture from the corn kernel is 345.22 kW and the exergy efficiency of the drying chamber ranges from 14.81% to 40.10%. The average cost of producing 1 GJ exergy for removing water from wet corn kernels is USD 25.971, while the average cost of removing 1 kg water is USD 0.159. These results might help to further understand the drying process from the exergoeconomic perspective and aid formulation of a scientific index for agricultural product industrial drying. Additionally, the results also indicated that, from an energy perspective, the combustion chamber should be firstly optimized, while the drying chamber should be given priority from the exergoeconomics perspective. The main results would be helpful for further optimizing the drying process from both energetic and economic perspectives and provide new thinking about agricultural product industrial drying from the perspective of exergoeconomics.

Estimation of the Reliability of a Stress-Strength System from Poisson Half Logistic Distribution.

This paper discussed the estimation of stress-strength reliability parameter R=P(Y

Identification and genomic sequence analysis of a new Spodoptera exigua multiple nucleopolyhedrovirus, SeMNPV-QD, isolated from Qingdao, China.

A new beet armyworm (Spodoptera exigua) multiple nucleopolyhedrovirus SeMNPV-QD was isolated from dead larvae in the field in Qingdao, Shandong, China. The virus has a polyhedron size of 1.39 ±â€¯0.28 µm, and typical virions contain one to seven nucleocapsids per envelope. SeMNPV-QD only infects the larvae of S. exigua; it does not infect larvae of S. litura, Agrotis ipsilon, A. segetum, Bombyx mori, Hyphantria cunea, or Stilpnotia salicis, and thus, has higher host specificity. SeMNPV-QD has a circular double-stranded DNA genome of 128,525 bp with a GC content of 37.41% and 127 putative open reading frames (ORF), each of which encodes more than 50 amino acids. These were identified and annotated in the SeMNPV-QD genome, accounting for 87.53% of the whole genome. Phylogenetic analysis of 38 core genes of the baculovirus confirmed that SeMNPV-QD is a Group II Alphabaculovirus and is most closely related to SeMNPV American isolate (SeMNPV-US1), S. litura nucleopolyhedrovirus II (SpliNPV-II), S. frugiperda multiple nucleopolyhedrovirus (SfMNPV), A. segetum nucleopolyhedrovirus (AgseNPV), A. segetum nucleopolyhedrovirus B (AgseNPV-B) and A. ipsilon multiple nucleopolyhedrovirus (AgipNPV). The pairwise distance of the nucleotide sequences of lef-8, lef-9, polh and concatenated lef-8/lef-9/polh fragments between SeMNPV-QD and several sister viruses mentioned above were all above 0.05 substitutions/site. SeMNPV-QD has 123 ORFs similar to those of SeMNPV-US1, and the genomic similarity was 45.8%. Compared to SeMNPV-US1, SeMNPV-QD has four additional ORFs such as two baculovirus repeat ORF (bro) genes, bro-1, bro-2, orf39 and orf95, but lacks 17 ORFs that have no effect on viral transcription and replication. The above results indicate that SeMNPV-QD is a new species of S. exigua multiple nucleopolyhedrovirus.

Efficient killing of radioresistant breast cancer cells by cytokine-induced killer cells.

Recurrence of breast cancer after radiotherapy may be partly explained by the presence of radioresistant cells. Thus, it would be desirable to develop an effective therapy against radioresistant cells. In this study, we demonstrated the intense antitumor activity of cytokine-induced killer cells against MCF-7 and radioresistant MCF-7 cells, as revealed by cytokine-induced killer-mediated cytotoxicity, tumor cell proliferation, and tumor invasion. Radioresistant MCF-7 cells were more susceptible to cytokine-induced killer cell killing. The stronger cytotoxicity of cytokine-induced killer cells against radioresistant MCF-7 cells was dependent on the expression of major histocompatibility complex class I polypeptide-related sequence A/B on radioresistant MCF-7 cells after exposure of cytokine-induced killer cells to sensitized targets. In addition, we demonstrated that cytokine-induced killer cell treatment sensitized breast cancer cells to chemotherapy via the downregulation of TK1, TYMS, and MDR1. These results indicate that cytokine-induced killer cell treatment in combination with radiotherapy and/or chemotherapy may induce synergistic antitumor activities and represent a novel strategy for breast cancer.

Kinetic effect of oestrogen on secretion of prostaglandins E2 and F2α in bovine oviduct epithelial cells.

This study aimed to investigate the effect of oestrogen on prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) secretion in bovine oviduct epithelial cells. Bovine oviduct epithelial cells were obtained from the lumen of fresh bovine oviducts. Quantitative real-time polymerase chain reaction and in-cell western assays were used to measure PGE2 and PGF2α synthase activity and enzyme-linked immunosorbent assays were used to detect the concentrations of the two prostaglandins in extracellular fluid. We observed that oestradiol caused a short-term increase in cyclo-oxygenase-2 (COX-2), which stimulated PGE2 and PGF2α secretion, and that a subsequent decrease in COX-2 and an increase in cyclo-oxygenase-1 (COX-1) produced a high PGE2:PGF2α ratio. These findings reflect the dynamic change in PGE2 and PGF2α levels under the influence of oestrogen, which may be essential for fertilisation.

Indirect interactions between arbuscular mycorrhizal fungi and Spodoptera exigua alter photosynthesis and plant endogenous hormones.

Peanut (Arachis hypogaea Linn. cv: Luhua 11) and tomato (Lycopersicon esculentum Mill. cv: Zhongshu 4) were inoculated with arbuscular mycorrhizal fungi (AMF) Funneliformis mosseae BEG167 (Fm), Rhizophagus intraradices BEG141 (Ri), and Glomus versiforme Berch (Gv), and/or Spodoptera exigua (S. exigua) under greenhouse conditions. Results indicated that feeding by S. exigua had little influence on colonization of peanut plants by AMF, but improved colonization of tomato by Fm and Gv. Feeding by S. exigua had little influence on leaf net photosynthetic rate, transpiration rate, and stomatal conductance of nonmycorrhizal peanut plants but significantly improved net photosynthetic rate and transpiration rate of mycorrhizal plants of both hosts. AMF with or without S. exigua inoculation improved host plant photosynthetic characteristics, growth, and hormone status. Fm showed maximum beneficial effects, followed by Gv. The concentrations and ratios of phytohormones abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellin (GA), zeatin riboside (ZR), and jasmonic acid (JA) in the leaves of the host plants were changed due to the interaction between AMF and S. exigua. Generally, AMF with or without S. exigua inoculation increased the concentrations of GA, ZR, and JA and the ratios of IAA/ABA, GA/ABA, ZR/ABA, and IAA + GA + ZR/ABA, while feeding by S. exigua on nonmycorrhizal plants showed the opposite effect. The concentration of JA in the leaves of peanut and tomato inoculated with Fm or Fm + S. exigua was 1.9 and 1.9 times and 2.5 and 2.7 times, respectively, greater than that of the controls inoculated with neither. There was a negative correlation between the JA concentration and the survival percentage of S. exigua larva. We conclude that indirect interactions between AMF and insect herbivores changed the photosynthetic and hormone characteristics, and ratios of phytohormones, thereby revealing mechanisms of belowground-aboveground interactions.

Diffusion flux of phosphorus nutrients at the sediment-water interface of the Ulansuhai Lake in northern China.

Overlying water and sediment samples were collected from 11 locations in Ulansuhai Lake in June of 2012 to determine the concentration of dissolved inorganic phosphorus (DIP) in the interstitial water, overlying water and sediment and to estimate the diffusion flux of DIP at the sediment-water interface. The DIP levels in overlying water were 0.004-0.185 mg/L (average = 0.062 mg/L), while they were 0.05-0.25 mg/L (average = 0.124 mg/L) in the interstitial water in the 0-2 cm surface sediment. Moreover, the annual mean exchange flux of DIP in the sediment was between -0.092 mg/m2·d and 0.053 mg/m2·d, and this occurred via internal source action in most areas. After area weighting, it is estimated that the exchange capacity of DIP at the sediment-water interface of the Ulansuhai Lake is 1.30 t/a. These findings indicate internal loading of phosphorus in sediment of the Ulansuhai Lake; thus, the diffusion of DIP in the interstitial water has effects on the lake, with a degree of influence of 2.7% to 81.5%.

Evaluation of the applicability of the SWAT model in an arid piedmont plain oasis.

Hetao Oasis is located in a typical piedmont alluvial plain bounded by the Langshan Mountain Range in the north, desert in the west, and the Yellow River in the south. Agricultural activities within the oasis significantly impact the hydrological cycle and water quality in downstream locations. The research uses the Soil and Water Assessment Tool (SWAT) for a piedmont plain by defining the watershed boundary as coinciding with the natural mountain ridge, the border between the oasis and the desert, and the Yellow River. The model simulates water discharge with coefficient of determination and a Nash-Sutcliffe model efficiency of 0.78 and 0.62 during model calibration, and 0.75 and 0.69 during model validation, suggesting that delineation of the watershed as carried out in this research is suitable for piedmont plain topography. From the results, the mountains contribute 28.4% to the water discharge at the outlet of the watershed, and water-use efficiency of irrigated water is about 40%, which is consistent with field-based measurements. Methodologies used in delineating watershed boundaries and parameterizing SWAT provide a solid foundation for water balance studies in other regions of the world with similar topography.

Prostanoid receptors EP2, EP4, and FP are regulated by estradiol in bovine oviductal smooth muscle.

Gamete and embryo transport is an important function of the oviduct. This transport involves both smooth muscle contraction and epithelial cell secretions, the former of which is mediated by prostaglandins (PGs) and their receptors. Our aim was to study the regulation of prostaglandin E2 and prostaglandin F2α receptors (EP2, EP4, and FP receptor) by estradiol in bovine oviduct smooth muscle. EP2, EP4, and FP receptor mRNA and protein expression was investigated using real-time RT-PCR and Western blot analyses, respectively. To evaluate the contraction or relaxation of cultured bovine oviductal smooth muscle tissue, peristalsis was used to assess contractile activity. EP2, EP4, and FP receptor mRNA and protein expression was increased in oviductal smooth muscle tissue after treatment with different concentrations of estradiol for various durations. The expression of all receptors peaked at an estradiol concentration of 10(-11)mol/L after 8h of treatment, whereas no increase in expression was observed after fulvestrant (a selective antagonist of E2 receptor) treatment, indicating that E2 interacts with specific E2 nuclear receptors to regulate EP2, EP4, and FP receptor expression. Although PGF2α and PGE2 induced both contraction and relaxation, no significant differences were found in contractility between the estradiol-treated and control groups, with both groups of cultured smooth muscle strips showing similar vitality. In conclusion, estradiol increases EP2, EP4, and FP receptor mRNA and protein expression in bovine oviductal smooth muscle when added for different periods of time and at different concentrations. Additionally, E2 is transported intracellularly and interacts with specific E2 nuclear receptors to regulate their expression.

Characteristics and indications of hydrogen and oxygen isotopes distribution in lake ice body.

Stable isotopes have been used to identify the characteristics of precipitation, evaporation, basin hydrology, and residence times. However, lakes in the cold regions are usually covered by ice for 5-6 months. To get a better understanding of stable isotopes characteristics and indications in lake ice bodies, ice and water were sampled during the icebound season in both the ice and water bodies in Dali Lake, and deuterium, oxygen-18 total nitrogen (TN), and the major ions were analyzed. The results showed that deuterium and oxygen-18 compositions (δD-δ¹8O) compositions in the ice body were greater than in the water body beneath, scattered on a straight line, and deviating downward from the global meteoric water line in the top right. The ice profile showed that the δD-δ¹8O compositions increased from the ice surface downward and decreased near to the bottom. In contrast, the TN and the major ions in the ice decreased from the ice surface downward and increased near to the bottom, meaning that the concentrations of δ¹8O had a negative correlation with the concentrations of TN and major ions. These indicated that stable isotopes can be used for tracing the nutriment and ion transport processes in the ice body.

[Heparin-treated dendritic cells promote Th0 to Th1 differentiation via the Toll-like receptor 3 in peripheral blood monocytes of patients with chronic hepatitis B].

OBJECTIVE: To investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB). METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis. RESULTS: TLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01). CONCLUSION: Heparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.

Systemic administration of a cyclic signal transducer and activator of transcription 3 (STAT3) decoy oligonucleotide inhibits tumor growth without inducing toxicological effects.

Hyperactivation of signal transducer and activator of transcription 3 (STAT3) has been linked to tumorigenesis in most malignancies, including head and neck squamous cell carcinoma. Intravenous delivery of a chemically modified cyclic STAT3 decoy oligonucleotide with improved serum and thermal stability demonstrated antitumor efficacy in conjunction with downmodulation of STAT3 target gene expression such as cyclin D1 and Bcl-X(L) in a mouse model of head and neck squamous cell carcinoma. The purpose of the present study was to determine the toxicity and dose-dependent antitumor efficacy of the cyclic STAT3 decoy after multiple intravenous doses in Foxn1 nu mice in anticipation of clinical translation. The two doses (5 and 10 mg/kg) of cyclic STAT3 decoy demonstrated a significant decrease in tumor volume compared with the control groups (mutant cyclic STAT3 decoy or saline) in conjunction with downmodulation of STAT3 target gene expression. There was no dose-dependent effect of cyclic STAT3 decoy on tumor volume or STAT3 target gene expression. There were no significant changes in body weights between the groups during the dosing period, after the dosing interval or on the day of euthanasia. No hematology or clinical chemistry parameters suggested toxicity of the cyclic STAT3 decoy compared with saline control. No gross or histological pathological abnormalities were noted at necropsy in any of the animals. These findings suggest a lack of toxicity of intravenous administration of a cyclic STAT3 decoy oligonucleotide. In addition, comparable antitumor effects indicate a lack of dose response at the two dose levels investigated.