Stamped production of single-crystal hexagonal boron nitride monolayers on various insulating substrates.

Controllable growth of two-dimensional (2D) single crystals on insulating substrates is the ultimate pursuit for realizing high-end applications in electronics and optoelectronics. However, for the most typical 2D insulator, hexagonal boron nitride (hBN), the production of a single-crystal monolayer on insulating substrates remains challenging. Here, we propose a methodology to realize the facile production of inch-sized single-crystal hBN monolayers on various insulating substrates by an atomic-scale stamp-like technique. The single-crystal Cu foils grown with hBN films can stick tightly (within 0.35 nm) to the insulating substrate at sub-melting temperature of Cu and extrude the hBN grown on the metallic surface onto the insulating substrate. Single-crystal hBN films can then be obtained by removing the Cu foil similar to the stamp process, regardless of the type or crystallinity of the insulating substrates. Our work will likely promote the manufacturing process of fully single-crystal 2D material-based devices and their applications.

Sodium-Alginate-Functionalized Silver Nanoparticles for Colorimetric Detection of Dimethoate.

Sodium alginate (SA) was used to functionalize the surfaces of silver nanoparticles (AgNPs) to form SA-AgNPs for sensing dimethoate with a rapid and sensitive visual readout. UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and zeta potential measurements were used to characterize SA-AgNPs that were synthesized under the ideal conditions. SA-AgNPs were spherical with an average size of 14.6 nm. The stability of SA-AgNPs was investigated with changes in pH, salinity, and storage time. This colorimetric assay of dimethoate relied on the change in the absorption ratio (A475/A400) of SA-AgNPs, resulting in their aggregation caused by dimethoate, leading to a visual change for SA-AgNPs from yellow to pale yellow. As a result, the absorption ratio (A475/A400) of SA-AgNPs showed good linearity in the range of 0.05 to 2.0 ppm (R2 = 0.9986) with a limit of detection (LOD) of 30 ppb. Adding other pesticides did not significantly change the absorption ratio of SA-AgNPs, indicating its high selectivity as a colorimetric assay. The sensor was successfully used to detect dimethoate in actual water samples.

Designed growth of large bilayer graphene with arbitrary twist angles.

The production of large-area twisted bilayer graphene (TBG) with controllable angles is a prerequisite for proceeding with its massive applications. However, most of the prevailing strategies to fabricate twisted bilayers face great challenges, where the transfer methods are easily stuck by interfacial contamination, and direct growth methods lack the flexibility in twist-angle design. Here we develop an effective strategy to grow centimetre-scale TBG with arbitrary twist angles (accuracy, <1.0°). The success in accurate angle control is realized by an angle replication from two prerotated single-crystal Cu(111) foils to form a Cu/TBG/Cu sandwich structure, from which the TBG can be isolated by a custom-developed equipotential surface etching process. The accuracy and consistency of the twist angles are unambiguously illustrated by comprehensive characterization techniques, namely, optical spectroscopy, electron microscopy, photoemission spectroscopy and photocurrent spectroscopy. Our work opens an accessible avenue for the designed growth of large-scale two-dimensional twisted bilayers and thus lays the material foundation for the future applications of twistronics at the integration level.

Heterogeneous integration of InP and Si3N4 waveguides based on interlayer coupling for an integrated optical gyroscope.

In this study, we demonstrate a novel, to the best of our knowledge, integrated indium phosphide (InP) and silicon nitride (Si3N4) waveguide platform, which is based on interlayer coupling, to achieve heterogeneous integration of a photodetector and waveguide ring resonator firstly. In order to improve the gyro bias stability, the Si3N4 and InP waveguides were designed with a high polarization extinction ratio and ultra-low loss. Three-dimensional finite difference time domain methods are used to optimize the InP taper dimensions to provide efficient optical coupling between the Si3N4 and InP waveguides. The optical coupler with a length of 100 µm is designed to achieve optical coupling between the Si3N4 and InP waveguides while maintaining its state of polarization all the way from the taper waveguides. The coupling efficiency of the optimized interlayer coupler has been improved to about 99.5%.

Identification of 24 Rana Species Including Rana dybowskii and Rana chensinensis Based on COⅠ Sequences / 中国实验方剂学杂志

Objective:To identify 24 <italic>Rana</italic> species such as <italic>Rana dybowskii</italic> by mitochondrial cytochrome C oxidase subunit I （<italic>CO</italic>Ⅰ） gene-based DNA barcoding and build the neighbour-joining （NJ） tree for hierarchical cluster analysis， so as to provide a basis for the identification and classification of <italic>Rana</italic> species as well as the discovery of new species. Method:<italic>R. dybowskii</italic>， <italic>R. chensinensis</italic>， <italic>R. amurensis</italic>， <italic>R. culaiensi</italic>s， and <italic>R. huanrenesis</italic>， ten for each species， were collected for DNA extraction and polymerase chain reaction （PCR） amplification<italic> </italic>and sequencing. A total of 50 <italic>CO</italic>Ⅰ gene sequences were obtained. Then 163 <italic>CO</italic>Ⅰ gene sequences for 24 species of <italic>Rana</italic> and one <italic>CO</italic>Ⅰ gene sequence for <italic>Pelophylax</italic>，<italic> Odorrana</italic>， <italic>Nidirana</italic>， <italic>Hylarana</italic>， and <italic>Amolops</italic> were harvested from GenBank. After sequence alignment by MEGA X， the parsimony-informative sites of <italic>CO</italic>Ⅰ gene sequences were analyzed and the intraspecific and interspecific genetic distances were calculated， followed by the built of NJ tree and hierarchical cluster analysis. Result:The <italic>CO</italic>Ⅰ gene sequences of 24<italic> Rana</italic> species including <italic>R. dybowskii</italic> were 554 bp in length and there were 210 parsimony-informative sites in total. The intraspecific genetic distance of each species was smaller than 2%. Except that the interspecific genetic distance between <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> was 0.004， the genetic distances between the other species ranged from 0.024 to 0.228. <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> were clustered into one branch and some <italic>R. dybowskii</italic> and <italic>R. uenoi</italic> into one branch. There were two separate branches for <italic>R. chensinensis</italic> and the other species were all clustered independently. Conclusion:<italic>CO</italic>Ⅰ-based DNA barcoding enabled the identification of 24 species of <italic>Rana</italic> including <italic>R.dybowskii</italic>. The findings supported that <italic>R. sangzhiensis</italic>， <italic>R. zhengi</italic>， <italic>R. coreana</italic>， and <italic>R. kunyuensis</italic> were the same species. One branch of <italic>R. chensinensis </italic>might be one of the four undownloaded species in Ranidae or a new species. The results have demonstrated that <italic>CO</italic>Ⅰ-based DNA barcoding allows not only the identification of 24 species of Rana including <italic>R. dybowskii </italic>but also the classification of ranidae species and the discovery of new species or subspecies.

Synthesis method optimization and biodistribution study of 18F-T807 on TRACERlab FXFN synthesizer / 药学实践杂志

Objective To optimize the synthesis method of 18F-T807 and study preliminary biodistribution. Methods 18F-T807 was synthesized using an optimized method in TRACERlab FXFN synthesizer with a t-BOC（t-Butyloxy carbonyl）-protected 18F-T807 precursor NPPI-9 as starting material, improving experimental conditions for synthesis, then QC and biodistribution study in Wistar rats conducted. Results The improved synthesis conditions increased the synthesis yield from 20.5%±6.1% to 25.7%±5.8%. QC met the standard. Wistar rats had higher intake in kidney, liver, blood and lowest intake in brain, heart, lung. Conclusion The optimized synthesis method to synthesize 18F-T807 is simple and easy, and high yield, which can meet the needs of scientific research and clinical practice.

Hepatocytes paradoxically affect intrahepatic IFN-γ production in autoimmune hepatitis due to Gal-9 expression and TLR2/4 ligand release.

Hepatocytes are the targets in autoimmune hepatitis (AIH) that results in T cell-dependent liver injury. However, hepatocytes may also affect the hepatic T cells in AIH, but the underlying mechanisms are not fully understood. Here we report that hepatocytes could secrete galectin-9 (Gal-9) to suppress the intrahepatic production of Th1 cytokine IFN-γ and restrict AIH development, but hepatocyte damage resulted in opposite effects due to release of TLR2/4 ligands that promoted the intrahepatic production of IL-1ß, IL-6, and IL-12. Through Tim-3, Gal-9 could efficiently suppress the intrahepatic T cell activation despite presence of TLR2/4 ligands, thus attenuating Th1 response in AIH. Intriguingly, intrahepatic IL-6/IL-12 suppressed the effect of TGF-ß on Treg cells. Therefore, in AIH, Gal-9 promoted Foxp3 expression and function of hepatic Treg cells through TL1A signaling, although Treg function was still impaired, compared with that in naive state. Due to its promoting effect on Treg function, together with its effect on T effector cells in a Tim-3-independent way, Gal-9 could attenuate intrahepatic IFN-γ production by hindering the increase of hepatic CD4+CD43+ T cells resulting from extrahepatic T cell activation. TLR2/4 ligands attenuated the effects of Gal-9 on Treg cells and CD4+CD43+ T cells by increasing intrahepatic IL-6 and IL-12. Blocking TLR2/4 ligands could efficiently suppress intrahepatic IFN-γ production, liver injury, and hepatic fibrosis. These findings suggest that hepatocytes paradoxically affect Th1 response in AIH due to Gal-9 expression and TLR2/4 ligands release, and that targeting TLR2/4 signaling may provide an important approach in the therapeutic strategy for AIH.

Chemical induced inflammation of the liver breaks tolerance and results in autoimmune hepatitis in Balb/c mice.

Autoimmune hepatitis (AIH) is a chronic liver disease mediated by immunity, and could lead to liver fibrosis and hepatocellular carcinoma. However, the mechanisms for breaking hepatic tolerance and driving AIH still remain elusive. We herein reported that the non-specific liver inflammation triggered by carbon tetrachloride (CCl4) recruited high numbers of CD4+T, CD8+T and B cells, and elevated the expression of proinflammaitory cytokines in Balb/c mice, further breaking liver tolerance and inducing autoimmune response, AIH inflammation and liver fibrosis in the presence of CYP2D6 antigen mimicry. In contrast, adenovirus infection could not break liver tolerance and induce AIH in Balb/c mice even in the presence of CYP2D6 antigen mimicry. These results suggested that genetic predisposition could determine liver tolerance in Balb/c mice. The chemical induced inflammation in the liver breaks tolerance and might be considered important for the initiation and development of AIH in Balb/c mice.

TGF-ß1 and TNF-α synergistically induce epithelial to mesenchymal transition of breast cancer cells by enhancing TAK1 activation.

TGF-ß1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-ß1 alone. So far, the mechanisms underlying the induction of TGF-ß1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-ß1. Intriguingly, TGF-ß1 could cooperate with TNF-α to promote the EMT and invasiveness of breast cancer cells. The prolonged co-stimulation with TGF-ß1 and TNF-α could enhance the sustained activation of Smad2/3, p38 MAPK, ERK, JNK and NF-κB pathways by enhancing the activation of TAK1, which was mediated by the gradually up-regulated TßRs. Except for JNK, all of these pathways were required for the effects of TGF-ß1 and TNF-α. Importantly, the activation of p38 MAPK and ERK pathways resulted in a positive feed-back effect on TAK1 activation by up-regulating the expression of TßRs, favoring the activation of multiple signaling pathways. Moreover, SLUG was up-regulated and required for the TGF-ß1/TNF-α-induced EMT and invasiveness. In addition, SLUG could also enhance the activation of signaling pathways by promoting TßRII expression. These findings suggest that the up-regulation of TßRs contributes to the sustained activation of TAK1 induced by TGF-ß1/TNF-α and the following activation of multiple signaling pathways, resulting in EMT and invasiveness of breast cancer cells.

IL-37 suppresses the sustained hepatic IFN-γ/TNF-α production and T cell-dependent liver injury.

T cell-dependent liver injury is an important reason for the massive hepatic damage and cirrhosis. So far it is unclear whether the development of the disease could be efficiently suppressed by anti-inflammatory cytokine that modulates innate immune cells. Here we report that anti-inflammatory cytokine IL-37 could efficiently suppress the sustained hepatic expression of IFN-γ and TNF-α, two critical cytokines for inducing hepatocyte apoptosis and liver fibrosis in T cell-dependent liver injury. IL-37 could directly suppress IFN-γ/TLR4 ligand-induced M1 activation of macrophages, thus reducing the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-12. Moreover, IL-37 attenuated Th1 response in vivo and increased the expression of Th2 cytokines IL-4 and IL-13, which in turn promoted M2 activation of macrophages in the liver. The increase of M2 activation not only further reduced TNF-α, IL-1ß and IL-12 expression, but also increased IL-10 and IL-1Ra expression in macrophages, thus more efficiently suppressing the hepatic IFN-γ expression. By suppressing IFN-γ/TNF-α expression, IL-37 suppressed the up-regulation and activation of MLKL that drives hepatocellular necrosis in T cell-dependent liver damage. Accordingly, IL-37 efficiently reduced liver injury and hepatic inflammation after the repeated ConA challenge and the induction of autoimmune hepatitis, and also suppressed hepatic fibrosis resulting from the sustained liver damage. This study showed that the direct and indirect effect of IL-37 on macrophages could reduce the hepatic TNF-α expression, and also modulate IL-1ß/IL-12 and IL-10/IL-1Ra expression to suppress the hepatic IFN-γ expression, thus suppressing the development of T cell-dependent liver injury such as autoimmune hepatitis.

C/EBPß enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation.

Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPß, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPß, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPß can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPß may provide more precise therapeutic options in ovarian cancer.

TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression.

Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4+CD25+ Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl4/CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH.

IL-35 induces N2 phenotype of neutrophils to promote tumor growth.

IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1ß and IL-6. IL-1ß stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.

Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation.

Circulating tumor cells (CTCs) have been studied well in the prognosis for malignant diseases as liquid biopsy, but their contribution to tumor metastasis is not clearly defined. Here we report that CTCs could promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in vivo could effectively abrogate the promoting effect of CTCs on tumor cell metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was augmented, whereas the antitumor function of neutrophils was suppressed. Mechanically, CTC-derived ligands for TLR2 and TLR4 (TLR2/4) induced the systemic inflammation, thus increasing the production of proinflammatory cytokines such as G-CSF and IL-6 that could induce the conversion of neutrophil function from tumor-suppressing to tumor-promoting. Moreover, CTCs induced the production of endogenous TLR2/4 ligands such as S100A8, S100A9, and SAA3, which may amplify the stimulating effect that induces the expression of proinflammatory cytokines. The promoting effect of CTCs on tumor cell metastasis could be abrogated by suppressing inflammatory response with IL-37, an anti-inflammatory cytokine, or blocking CTC-derived ligands for TLR2/4. Identification of the metastatic axis of CTCs/systemic inflammation/neutrophils may provide potential targets for preventing tumor cell metastasis.

Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR.

[One-stage reconstruction of distal urethra with free graft of tublar oral mucosa ].

Objective To investigate the therapeuctic effect of one-stage reconstruction of distal urethra with free graft of tublar oral mucosa. . Methods: Two strips of oral mucosa graft(0.4-0.6 cm in width),were harvested and sutured around an oiled silk roll to form mucosa tube. The mucosa tube was used to reconstruct distal urethra. Postoperative pressure dressing and earlier urination were recommended Results: From May 2007 to October 2015,16 cases with distal urethra defect or stenosis were treated with this method. The urethra defect was 2-4 cm in length. Urethral fistula happened in 3 patients. All the other 13 cases healed primarily.10 cases were followed up for 1-5 years by telephone with normal function. Conclusions: One-stage reconstruction with free graft of bulbar oral mucosa is suitable and reliable for distal urethra defect less than 4 cm in length.

Biochemical changes in the serum and placenta of rats with gestational diabetes after transplantation of human placental mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Human placental mesenchymal stem cells can improve the blood glucose level of diabetes mellitus rats and gestational diabetes rats, but little is reported on its effect on glucagon, adiponectin, and tumor necrosis factor-α in the serum and placental tissues. OBJECTIVE: To investigate the effects of human placental mesenchymal stem cells on the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues in gestational diabetes rats. METHODS: A rat model of gestational diabetes was made by high-fat and high-sugar diet plus low-dose injection of streptozotocin. Passage 3 human placental mesenchymal stem cell suspension (1×1010 cells/L, 0.5 mL) was injected into gestational diabetes rats at gestational days 4 and 11 (4- and 11-day intervention groups). Meanwhile, control rats were given the same amount of normal saline. At 20 days of gestation, blood samples from the abdominal aorta were extracted, and then cesarean section was made to remove the placenta in the gestational diabetes rats. ELISA and real-time PCR were used to detect the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues, respectively. RESULTS AND CONCLUSION: (1) The serum and placental levels of glucagon, adiponectin and tumor necrosis factor-α showed no differences between the 4- and 11-day intervention groups (P > 0.05). (2) Compared with the control group, significantly increased serum adiponectin level and significantly decreased placental glucagon mRNA expression were found in the 4-day intervention group (P < 0.05). (3) Compared with the control group, the serum adiponectin level and the placental glucagon level both had a significant decrease in the 11-day intervention group (P < 0.01), while the serum level of tumor necrosis factor-α was significantly decreased (P < 0.01). To conclude, transplantation of human placental mesenchymal stem cells can vary the adiponectin and glucagon levels, which provides a new research idea and basis for the further study on the possible mechanism of placental mesenchymal stem cells to improve blood glucose level in gestational diabetes rats. Additionally, it is worthy while to notice that gestational diabetes rats given placental mesenchymal stem cells in the early or late pregnancy show no effects on the above indicators.

14,15-EET induces the infiltration and tumor-promoting function of neutrophils to trigger the growth of minimal dormant metastases.

Infiltrating neutrophils are known to promote in the development of tumor. However, it is unclear whether and how neutrophils are involved in triggering the growth of dormant metastases. Here we show that 14,15-epoxyeicosatrienoic acid (14,15-EET) can trigger the growth of dormant micrometastases by inducing neutrophilic infiltration and converting neutrophil function. 14,15-EET triggered neutrophil infiltration in metastatic lesions by activating STAT3 and JNK pathways to induce the expression of human IL-8 and murine CXCL15 in corresponding tumor cells. The continuous expression of hIL-8/mCXCL15 was maintained by the sustained and enhanced activation of JNK pathway. 14,15-EET up-regulated miR-155 expression by activating STAT3 and JNK pathways. miR-155 in turn down-regulated the expression of SHIP1 and DET1, thus augmenting the activation of JNK and c-Jun. Moreover, the function of neutrophils was converted from tumor-suppressing to tumor-promoting by 14,15-EET in vivo. By inducing the production of G-CSF/IL-6 in vivo, 14,15-EET induced the enhancement of STAT3 activation in neutrophils to increase MMP-9 expression and decrease TRAIL expression. Neutrophil-derived MMP-9 was required for 14,15-EET to induce angiogenesis during the growth of dormant micrometastases. Depleting neutrophils or inhibiting hIL-8/mCXCL15 up-regulation resulted in the failure of 14,15-EET to promote the development of micrometastases. These findings reveal a mechanism through which the infiltration and tumor-promoting function of neutrophils could be induced to trigger the growth of dormant metastases, which might be a driving force for the tumor recurrence based on dormant metastases.