Single-sEV profiling identifies the TACSTD2 + sEV subpopulation as a factor of tumor susceptibility in the elderly.

BACKGROUND: Aging is a very complex physiological phenomenon, and sEVs are involved in the regulation of this mechanism. Serum samples from healthy individuals under 30 and over 60 years of age were collected to analyze differences in sEVs proteomics. RESULTS: Based on PBA analysis, we found that sEVs from the serum of elderly individuals highly express TACSTD2 and identified a subpopulation marked by TACSTD2. Using ELISA, we verified the upregulation of TACSTD2 in serum from elderly human and aged mouse. In addition, we discovered that TACSTD2 was significantly increased in samples from tumor patients and had better diagnostic value than CEA. Specifically, 9 of the 13 tumor groups exhibited elevated TACSTD2, particularly for cervical cancer, colon cancer, esophageal carcinoma, liver cancer and thyroid carcinoma. Moreover, we found that serum sEVs from the elderly (especially those with high TACSTD2 levels) promoted tumor cell (SW480, HuCCT1 and HeLa) proliferation and migration. CONCLUSION: TACSTD2 was upregulated in the serum of elderly individuals and patients with tumors, and could serve as a dual biomarker for aging and tumors.

A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling.

MP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-HJ-1b and colchicine increased reactive oxygen species and malondialdehyde levels and decreased reduced glutathione levels, suggesting that they promoted ferroptosis in HeLa cells. Specifically, MP-HJ-1b downregulated SLC7A11 and GPX4 to enhance the classical pathway of ferroptosis, while colchicine upregulated LC3A/B-II and enhanced autophagy. Clinically, the serum concentrations of ferrous ions, reduced glutathione, and Hcy were higher in cervical cancer patients than in healthy individuals. ALT, AST, Cho, HDL-C, and LDL-C levels were decreased in the serum of patients. Our study expands understanding of the way MP-HJ-1b promotes cell death and enriches research on microtubule inhibitors in the ferroptosis field.

Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes.

Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-ß1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-ß1/Smads axis to promote metastasis.

Dysregulation of TMEM16A impairs oviductal transport of embryos.

Ectopic pregnancy is an acute abdominalgia in obstetrics and gynecology, especially in fallopian tubal pregnancy. The ion channel protein transmembrane protein 16A (TMEM16A) is widely distributed in various tissues, even in the oviduct. In this study, we showed that TMEM16A was expressed in the human fallopian tube and was upregulated in patients with tubal pregnancy. By measuring isolated fallopian tube tissues, we found that TMEM16A was involved in regulating not only the contraction of muscle strips but also the beat frequency of cilia. In addition, pharmacological activation or inhibition of TMEM16A could lead to retention of embryos in oviducts. Moreover, the embryos in oviducts were delayed in development and some of them had malformations and deletions. The total number of embryos in the oviducts and uterus was significantly less than that of the control group. Furthermore, we detected changes in the level of m6A methylation, where the relevant writers and readers were reduced in tubal tissues from tubal pregnancies. In m6A mRNA methylation, writers catalyze the addition of methyl groups to cytosine residues and readers bind to the methyl groups and affect gene translation. In human fallopian tube epithelial cell line FTE187, we found that interference with methyltransferase 3 (METTL3) expression increased TMEM16A, suggesting that TMEM16A might be regulated by m6A methylation. In general, our study revealed a novel regulatory point for embryo transport and development, introducing a new role for the diagnosis and treatment of tubal pregnancy.NEW & NOTEWORTHY The ion channel protein TMEM16A is expressed in the epithelium and smooth muscle of the human fallopian tube and is upregulated in patients with tubal pregnancy. TMEM16A is involved in regulating the smooth muscle contraction and the cilia beating. Dysregulated TMEM16A may result in embryo retention in the oviduct and delayed early embryo development. Our study reveals a new regulatory point for embryo transport and development.

Sparse 2-D optical phased array with large grating-lobe-free steering range based on an aperiodic grid.

Two-dimensional (2-D) optical phased arrays (OPAs) usually suffer from limited scan ranges and small aperture sizes. To overcome these bottlenecks, we utilize an aperiodic 32 × 32 grid to increase the beam scanning range and furthermore distribute 128 grating antennas sparsely among 1024 grid points so as to reduce the array element number. The genetic algorithm is used to optimize the uneven grid spacings and the sparse distribution of grating antennas. With these measures, a 128-channel 2-D OPA operating at 1550 nm realizes a grating-lobe-free steering range of 53° × 16°, a field of view of 24° × 16°, a beam divergence of 0.31° × 0.49°, and a sidelobe suppression ratio of 9 dB.

Polarization-insensitive antisymmetric multimode waveguide Bragg grating filter based on an SiN-Si dual-layer stack.

A polarization-insensitive multimode antisymmetric waveguide Bragg grating (MASWBG) filter based on an SiN-Si dual-layer stack is demonstrated. Carefully optimized grating corrugations patterned on the sidewall of a silicon waveguide and SiN overlay are used to perturbate TE and TM modes, respectively. Furthermore, the lateral-shift apodization technique is utilized to improve the sidelobe suppression ratio (SLSR). A good overlap between the passbands measured in TE and TM polarization states is obtained. Insertion losses, SLSRs, and 3-dB bandwidths of measured passbands in TE/TM polarizations are 1/1.72 dB, 18.5/19.1 dB, and 5.1/3.5 nm, respectively.

Silicon-based high-power traveling wave photodetector with inductive gain peaking.

We demonstrate Ge/Si high-power and high-speed distributed traveling wave photodetectors (TWPD) by using the inductive gain peaking technique. Input terminals of TW electrodes are open to enhance RF output efficiencies to output loads. Furthermore, optimized on-chip spiral inductors are incorporated at output terminals of TW electrodes to alleviate bandwidth degradations caused by the absences of matching impedances. A comprehensive equivalent circuit model is developed to calculate the frequency response of this scheme. It is used to optimize the design, and then is validated by measurement results. After inducing on-chip inductors, the bandwidths of 4-stage and 8-stage TWPDs are improved from 32 to 44 GHz and 16 to 24 GHz, respectively. Maximum RF output powers of 4-stage and 8-stage TWPDs with on-chip inductors are measured to be 5.7 dBm and 9.4 dBm at 20 GHz, respectively.

High linearity silicon DC Kerr modulator enhanced by slow light for 112 Gbit/s PAM4 over 2 km single mode fiber transmission.

We demonstrate a high efficiency, high linearity and high-speed silicon Mach-Zehnder modulator based on the DC Kerr effect enhanced by slow light. The two modulation arms based on 500-µm-long grating waveguides are embedded with PN and PIN junctions, respectively. A comprehensive comparison between the two modulation arms reveals that insertion loss, bandwidth and modulation linearity are improved significantly after employing the DC Kerr effect. The complementary advantages of the slow light and the DC Kerr effect enable a modulation efficiency of 0.85 V·cm, a linearity of 115 dB·Hz2/3, and a bandwidth of 30 GHz when the group index of slow light is set to 10. Furthermore, 112 Gbit/s PAM4 transmission over 2 km standard single mode fiber (SSMF) with bit error ratio (BER) below the soft decision forward error correction (SD-FEC) threshold is also demonstrated.

Inhibition of GABAA receptors in intestinal stem cells prevents chemoradiotherapy-induced intestinal toxicity.

Lethal intestinal tissue toxicity is a common side effect and a dose-limiting factor in chemoradiotherapy. Chemoradiotherapy can trigger DNA damage and induce P53-dependent apoptosis in LGR5+ intestinal stem cells (ISCs). Gamma-aminobutyric acid (GABA) and its A receptors (GABAAR) are present in the gastrointestinal tract. However, the functioning of the GABAergic system in ISCs is poorly defined. We found that GABAAR α1 (GABRA1) levels increased in the murine intestine after chemoradiotherapy. GABRA1 depletion in LGR5+ ISCs protected the intestine from chemoradiotherapy-induced P53-dependent apoptosis and prolonged animal survival. The administration of bicuculline, a GABAAR antagonist, prevented chemoradiotherapy-induced ISC loss and intestinal damage without reducing the chemoradiosensitivity of tumors. Mechanistically, it was associated with the reduction of reactive oxygen species-induced DNA damage via the L-type voltage-dependent Ca2+ channels. Notably, flumazenil, a GABAAR antagonist approved by the U.S. Food and Drug Administration, rescued human colonic organoids from chemoradiotherapy-induced toxicity. Therefore, flumazenil may be a promising drug for reducing the gastrointestinal side effects of chemoradiotherapy.

Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis.

BACKGROUND: Tumor necrosis factor receptor-associated factor 6 (TRAF6) can regulate the activation of inflammatory signaling pathways by acting as an E3 ubiquitin ligase, which enhances B cell activation. This study aimed to evaluate the expression of TRAF6 in the peripheral blood B cells of myasthenia gravis (MG) patients and analyze the relationships between TRAF6 expression and clinical characteristics. METHOD: In our study, the expression level of TRAF6 in peripheral blood B cells of 89 patients was measured by flow cytometry compared with that of healthy subjects. The effects of disease severity, MG classification and immunotherapy on TRAF6 expression level were also analyzed. RESULTS: In our study, TRAF6 expression was elevated in CD19+ B cells and CD19+CD27+ memory B cells in generalized MG (GMG) patients compared with ocular MG (OMG) patients (p = 0.03 and p = 0.03, respectively). There was a significant positive correlation between the TRAF6 expression level and disease severity in both OMG patients and GMG patients (CD19+ B cells: OMG: p < 0.001, r = 0.89; GMG: p = 0.001, r = 0.59; CD29+CD27+ B cells: OMG: p = 0.001, r = 0.80; GMG: p = 0.048, r = 0.38). TRAF6 expression was significantly elevated in CD19+ B cells and CD19+CD27+ memory B cells in GMG with acute aggravation compared with GMG in MMS (p = 0.009 and p = 0.028, respectively). In the eleven MG patients who were followed, TRAF6 expression in B cells and memory B cells was significantly decreased after treatment (p = 0.03 and p < 0.01, respectively). CONCLUSION: TRAF6 is potentially a useful biomarker of inflammation in patients with MG, and might be used to evaluate the effectiveness of treatment.

Ultra-compact silicon mode (de)multiplexer based on directional couplers with subwavelength sidewall corrugations.

Asymmetrical directional couplers aided with subwavelength sidewall corrugations are used to realize ultra-compact silicon mode (de)multiplexers at C-band. Three mode (de)multiplexers with ultra-short coupling lengths of 5.6/6.5/7.7 µm are designed to enable low-loss mode conversions between TE0 and TE1/2/3 modes. They are then cascaded to build a four-channel mode-division-multiplexing (MDM) link. The four mode channels present minimal on-chip insertion losses of 0.2/0.7/0.7/0.9 dB at their peak wavelengths. Measured cross talk levels of the four mode channels are better than -18.0/-19.1/-16.0/-18.2 dB within the wavelength range from 1530 nm to 1580 nm.

GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner.

GNA13, encoding one of the G protein alpha subunits of heterotrimeric G proteins that transduce signals of G protein-coupled receptors (GPCR), is frequently mutated in germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) with poor prognostic outcomes. Due to the "undruggable" nature of GNA13, targeted therapy for these patients is not available. In this study, we found that palmitoylation of GNA13 not only regulates its plasma membrane localization, but also regulates GNA13's stability. It is essential for the tumor suppressor function of GNA13 in GCB-DLBCL cells. Interestingly, GNA13 negatively regulates BCL2 expression in GCB-DLBCL cells in a palmitoylation-dependent manner. Consistently, BCL2 inhibitors were found to be effective in killing GNA13-deficient GCB-DLBCL cells in a cell-based chemical screen. Furthermore, we demonstrate that inactivating GNA13 by targeting its palmitoylation enhanced the sensitivity of GCB-DLBCL to the BCL2 inhibitor. These studies indicate that the loss-of-function mutation of GNA13 is a biomarker for BCL2 inhibitor therapy of GCB-DLBCL and that GNA13 palmitoylation is a potential target for combination therapy with BCL2 inhibitors to treat GCB-DLBCL with wild-type GNA13.

Trophoblast H2S Maintains Early Pregnancy via Regulating Maternal-Fetal Interface Immune Hemostasis.

CONTEXT: Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive. OBJECTIVE: To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion. DESIGN: First trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo. RESULTS: CBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual T-helper 1/T-helper 2 imbalance in mice, which was partially rescued by H2S donors. CONCLUSION: CBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.

Compact general interference hybrid-plasmonic multimode interferometers used for optical hybrid.

We propose three general interference multimode interferometers (MMIs) based on hybrid plasmonic waveguides (HPWs). Among them, the general 2×2 and 4×4 MMIs are designed for a 90° optical hybrid, while the 3×3 MMI is for a 120° optical hybrid. First, by considering the mode interference characteristics inside the multimode HPWs, a compromise between the number of guided modes and the device length is obtained at a determined height of the SiO2 interlayer of the HPW. Also, by analyzing the characteristics of multimode propagation in the HPW-MMI, it is found that the optimal positions of self-images would shift from their theoretical ones. In addition, tapered HPW sections are implemented to improve the coupling efficiencies for lights coupled into/out of the multimode section. Therefore, by optimizing the width and length of the multimode section, and especially the position of the input and output single-mode waveguides, the appropriate structure parameters of three HPW-MMIs are obtained, where the footprints of the 2×2, 3×3, and 4×4 HPW-MMIs are only 1.96×5.4 µm2, 2.18×12.0 µm2, and 2.52×11.5 µm2, respectively. The simulation results show that, at the wavelength of 1550 nm, the 2×2 HPW-MMI exhibits a transmission of 75.6%, a maximum transmissions imbalance of 0.55 dB, and a phase error of 3.68°; the 3×3 HPW-MMI exhibits a transmission of 69.2%, a maximum transmissions imbalance of 0.43 dB, and a phase error of 4.66°; and the 4×4 HPW-MMI exhibits a transmission of 68.5%, a maximum transmissions imbalance of 0.91 dB, and a phase error of 4.81°. All these performances meet the standard industry requirements.

A Novel Microtubule Inhibitor Overcomes Multidrug Resistance in Tumors.

Microtubule inhibitors as chemotherapeutic drugs are widely used for cancer treatment. However, the development of multidrug resistance (MDR) in cancer is a major challenge for microtubule inhibitors in their clinical implementation. From a high-throughput drug screen using cells transformed by oncogenic RAS, we identify a lead heteroaryl amide compound that blocks cell proliferation. Analysis of the structure-activity relationship indicated that this series of scaffolds (exemplified by MP-HJ-1b) represents a potent inhibitor of tumor cell growth. MP-HJ-1b showed activities against a panel of more than 1,000 human cancer cell lines with a wide variety of tissue origins. This compound depolymerized microtubules and affected spindle formation. It also induced the spike-like conformation of microtubules in vitro and in vivo, which is different from typical microtubule modulators. Structural analysis revealed that this series of compounds bound the colchicine pocket at the intra-dimer interface, although mostly not overlapping with colchicine binding. MP-HJ-1b displayed favorable pharmacological properties for overcoming tumor MDR, both in vitro and in vivo Taken together, our data reveal a novel scaffold represented by MP-HJ-1b that can be developed as a cancer therapeutic against tumors with MDR.Significance: Paclitaxel is a widely used chemotherapeutic drug in patients with multiple types of cancer. However, resistance to paclitaxel is a challenge. This study describes a novel class of microtubule inhibitors with the ability to circumvent multidrug resistance across multiple tumor cell lines. Cancer Res; 78(20); 5949-57. ©2018 AACR.

Identification of a novel protein complex containing ASIC1a and GABAA receptors and their interregulation.

Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are widely distributed within both the central and peripheral nervous systems. ASICs were modified by the activation of γ-aminobutyric acid receptors (GABAA), a ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity of GABAA receptors were also modulated by extracellular pH. However so far, the mechanisms underlying this intermodulation remain obscure. We hypothesized that these two receptors-GABAA receptors and ASICs channels might form a novel protein complex and functionally interact with each other. In the study reported here, we found that ASICs were modified by the activation of GABAA receptors either in HEK293 cells following transient co-transfection of GABAA and ASIC1a or in primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of ASIC1a also modifies the GABAA receptor-channel kinetics. Immunoassays showed that both GABAA and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABAA and ASIC1a or in primary cultured DRG neurons. Our results indicate that putative GABAA and ASIC1a channels functionally interact with each other, possibly via an inter-molecular association by forming a novel protein complex.

Dysregulation of hydrogen sulphide metabolism impairs oviductal transport of embryos.

Embryo retention in the fallopian tube is thought to lead to ectopic pregnancy, which is a significant cause of morbidity. Hydrogen sulphide (H2S) is a gaseotransmitter produced mainly by cystathionine-γ-lyase and cystathionine-ß-synthase. Here we show that cystathionine-γ-lyase and cystathionine -ß-synthase are ubiquitously distributed in human fallopian tube epithelium and that H2S signalling relaxes the spontaneous contraction of the human oviduct. Furthermore, an aberration in H2S signalling, either silenced or enhanced activity induced by pharmacologic or genetic methods, causes embryo retention and developmental delay in the mouse oviduct, which is partly reversed by administration of either GYY4137, a slow-releasing H2S donor, or NaHS. Our findings reveal a new regulatory mechanism for oviductal embryo transport.

GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation.

The present study aims to determine the role of γ-aminobutyric acid (GABA) signaling molecules in breast cancer metastasis. Our results reveal that GABAergic system exists in breast cancer cells. Both the GABA synthetic enzyme. (GAD65/67) and GABAB receptor are expressed in 4T1 mouse breast cancer cells, MCF-7 human breast cancer cells and human breast cancer tissue. Baclofen, a GABABR agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABABR antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway.

Chloroquine stimulates Cl- secretion by Ca2+ activated Cl- channels in rat ileum.

Chloroquine (CQ), a bitter tasting drug widely used in treatment of malaria, is associated gastrointestinal side effects including nausea or diarrhea. In the present study, we investigated the effect of CQ on electrolyte transport in rat ileum using the Ussing chamber technique. The results showed that CQ evoked an increase in short circuit current (ISC) in rat ileum at lower concentration (≤5×10(-4) M) but induced a decrease at higher concentrations (≥10(-3) M). These responses were not affected by tetrodotoxin (TTX). Other bitter compounds, such as denatoniumbenzoate and quinine, exhibited similar effects. CQ-evoked increase in ISC was partly reduced by amiloride(10(-4) M), a blocker of epithelial Na(+) channels. Furosemide (10(-4) M), an inhibitor of Na(+)-K(+)-2Cl(-) co-transporter, also inhibited the increased ISC response to CQ, whereas another Cl(-) channel inhibitor, CFTR(inh)-172(10(-5) M), had no effect. Intriguingly, CQ-evoked increases were almost completely abolished by niflumic acid (10(-4) M), a relatively specific Ca(2+)-activated Cl(-) channel (CaCC) inhibitor. Furthermore, other CaCC inhibitors, such as DIDS and NPPB, also exhibited similar effects. CQ-induced increases in ISC were also abolished by thapsigargin(10(-6) M), a Ca(2+) pump inhibitor and in the absence of either Cl(-) or Ca(2+) from bathing solutions. Further studies demonstrated that T2R and CaCC-TMEM16A were colocalized in small intestinal epithelial cells and the T2R agonist CQ evoked an increase of intracelluar Ca(2+) in small intestinal epithelial cells. Taken together, these results demonstrate that CQ induces Cl(-) secretion in rat ileum through CaCC at low concentrations, suggesting a novel explanation for CQ-associated gastrointestinal side-effects during the treatment of malaria.

Aberrant sphingolipid metabolism in the human fallopian tube with ectopic pregnancy.

Sphingosine 1-phosphate (S1P), a product of sphingomyelin metabolism, is generated via phosphorylation of sphingosine by sphingosine kinases (SphK). It acts via a family of G protein-coupled receptors or as an intracellular second messenger for agonists acting through the S1P receptors (S1P1-5). In our study, the expression of SphK1 and S1P1 was identified by immunohistochemistry and immunoblot. The concentration of S1P was measured using ELISA. The spontaneous contraction of isolated fallopian tube strips was determined by tension recording. Our results showed that SphK1 and S1P1 were localized in the fallopian tube epithelial cells. In addition, smooth muscle cells also contained S1P1. Compared with the intrauterine pregnancy group, SPHK1 and S1P1 were overexpressed in ectopic pregnancy. However, the S1P concentration within the human oviduct from ectopic pregnancy subjects was largely reduced than that from normal pregnancy subject. The results from tension recording indicated that exogenous and intracellularly generated S1P can regulate the spontaneous contraction of oviduct isolated from rats and human. In conclusion, the sphingolipid metabolism signal pathway functionally existed in the human fallopian tube. Aberrant sphingolipid metabolism in the human fallopian tube may be involved in ectopic pregnancy.