An acoustic bellows-type round window transducer for middle-ear implants.

BACKGROUND: This study describes the development of output devices for round window middle-ear. To overcome the problems of output devices that apply sound pressure directly to the round window, an acoustic bellows-type round window transducer was implemented by combining a small bellows, acoustic tube, and balanced armature driver. METHODS: The output characteristics of the proposed acoustic bellows-type round window transducer were confirmed through bench tests and distortion measurements. To compare the vibration transmission characteristics of the proposed transducer with those of sound pressure stimulation devices, an experiment was performed using four human temporal bones. FINDINGS: The average output magnitude of the acoustic bellows-type round window transducer was equivalent to sound pressure levels of 92, 96, and 108 dB for frequency ranges of <1, 1-2, and > 2 kHz, respectively. The results showed that the proposed transducer delivered vibration consistently without reducing the sound pressure level due to leakage, unlike the sound pressure stimulation device. INTERPRETATION: Therefore, the acoustic bellows-type round window transducer is a more stable and suitable output device for round window middle-ear implants than a sound pressure stimulation device. It is expected to overcome the limitations of sound pressure stimulation devices and to contribute to new technical solutions in the field of round window middle-ear implants development.

CMTM4 inhibits gastric tumorigenesis and metastasis.

Background: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC. Methods: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene CMTM4 was knocked down and overexpressed in human gastric adenocarcinoma cell line AGS. The gene CMTM4 was overexpressed in AGS cells and human gastric cell line SGC7901. Cell Counting Kit 8 (CCK-8) and cell clonogenic assays were used to analyze the proliferation of the GC cells. Flow cytometry was used to analyze the effects of CMTM4 on apoptosis and the cell cycle. Wound healing and transwell assays were used to analyze the migration and invasion of the gastric cells, respectively. The mechanism of CMTM4 in GC cells was explored using the tandem mass tags (TMTs) proteome and verified by western blot analysis. Results: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown enhanced gastric cell proliferation (P>0.05), migration (P>0.05), and invasion (P>0.05). Flow cytometry showed that CMTM4 promoted apoptosis and resulted in G1/S arrest in the GC cells. In addition, the proteome and western blot results showed that STAT1 was significantly upregulated, and the STAT1 signaling pathways were enriched in the GC cells overexpressing CMTM4. Conclusions: Our results suggest that CMTM4 plays a tumor-suppressive role in GC and may affect the growth, migration, and invasion of GC cells through the STAT1 signaling pathway. CMTM4 might have potential value as a prognosis marker and potential therapeutic target for GC therapy.

Quantification of the Uncertainty in Ultrasonic Wave Speed in Concrete: Application to Temperature Monitoring with Embedded Transducers.

This article presents an overall examination of how small temperature fluctuations affect P-wave velocity (Vp) measurements and their uncertainties in concrete using embedded piezoelectric transducers. This study highlights the fabrication of custom transducers tailored for long-term concrete monitoring. Accurate and reliable estimation of ultrasonic wave velocities is challenging, since they can be impacted by multiple experimental and environmental factors. In this work, a reliable methodology incorporating correction models is introduced for the quantification of uncertainties in ultrasonic absolute and relative velocity measurements. The study identifies significant influence quantities and suggests uncertainty estimation laws, enhancing measurement accuracy. Determining the onset time of the signal is very time-consuming if the onset is picked manually. After testing various methods to pinpoint the onset time, we selected the Akaike Information Criterion (AIC) due to its ability to produce sufficiently reliable results. Then, signal correlation was used to determine the influence of temperature (20 °C to 40 °C) on Vp in different concrete samples. This technique proved effective in evaluating velocity changes, revealing a persistent velocity decrease with temperature increases for various concrete compositions. The study demonstrated the capability of ultrasonic measurements to detect small variations in the state of concrete under the influence of environmental variables like temperature, underlining the importance of incorporating all influencing factors.

A Unique Time-Reversal Algorithm-Enabled Flexible Ultrasound Transducer with a Controllable Acoustic Field.

Flexible ultrasonic devices represent a feasible technology for providing timely signal detection and even a non-invasive disease treatment for the human brain. However, the deformation of the devices is always accompanied by a change in the acoustic field, making it hard for accurate focusing. Herein, we report a stable and flexible transducer. This device can generate a high-intensity acoustic signal with a controllable acoustic field even when the device is bent. The key is to use a low-impedance piezoelectric material and an island-bridge device structure, as well as to design a unique time-reversal algorithm to correct the deviation of signals after transcranial propagation. To provide an in-depth study of the acoustic field of flexible devices, we also analyze the effects of mechanical deformation and structural parameters on the corresponding acoustic response.

Dual-Wave ZnO Film Ultrasonic Transducers for Temperature and Stress Measurements.

ZnO film ultrasonic transducers for temperature and stress measurements with dual-mode wave excitation (longitudinal and shear) were deposited using the reactive RF magnetron sputtering technique on Si and stainless steel substrates and construction steel bolts. It was found that the position in the substrate plane had a significant effect on the structure and ultrasonic performance of the transducers. The transducers deposited at the center of the deposition zone demonstrated a straight columnar structure with a c-axis parallel to the substrate normal and the generation of longitudinal waves. The transducers deposited at the edge of the deposition zone demonstrated inclined columnar structures and the generation of dominant shear or longitudinal shear waves. Transducers deposited on the bolts with dual-wave excitation were used to study the effects of high temperatures in the range from 25 to 525 °C and tensile stress in the range from 0 to 268 MPa on ultrasonic response. Dependencies between changes in the relative time of flight and temperature or axial stress were obtained. The dependencies can be described by second-order functions of temperature and stress. An analysis of the contributions of thermal expansion, strain, and the speed of sound to changes in the time of flight was performed. At high temperatures, a decrease in the signal amplitude was observed due to the decreasing resistivity of the transducer. The ZnO ultrasonic transducers can be used up to temperatures of ~500 °C.

Enhancing Ultrasonic Echo Response of AlN Thin Film Transducer Deposited by RF Magnetron Sputtering.

Accurate measurement of the pretightening stress for bolts has great significance for improving the assembly quality and safety, especially in severe environments. In this study, AlN thin film transducers were deposited on GH4169 nickel base alloy bolts using the RF magnetron sputtering, enabling a systematic investigation into the correlation between structures and the intensity of ultrasonic echo signals. Employing the finite element method resulted in consistency with the experimental data, enabling further exploration of the enhancement mechanism. With the increasing thickness of both the piezoelectric layer and the electrode layer, the intensity of the ultrasonic echo signals saw a great enhancement. The maximum-intensity observed increase is 14.7 times greater than that of the thinnest layers. Specifically, the thicker piezoelectric layer improves its mechanical displacement, while the increased thickness of the electrode layer contributes to better densification. An electrode diameter of nearly 4 mm is optimal for an AlN thin film transducer of M8 bolts. For pretightening the stress measurement, the sample with a strong and stable echo signal shows a low measurement error of pretightening below ±2.50%.

Radiation Impedance of Rectangular CMUTs.

Recently, capacitive micromachined ultrasound transducers (CMUTs) with long rectangular membranes have demonstrated performance advantages over conventional piezoelectric transducers; however, modeling these CMUT geometries has been limited to computationally burdensome numerical methods. Improved fast modeling methods, such as equivalent circuit models, could help achieve designs with even better performance. The primary obstacle in developing such methods is the lack of tractable methods for computing the radiation impedance of clamped rectangular radiators. This paper presents a method that approximates the velocity profile using a polynomial shape model to rapidly and accurately estimate radiation impedance. The validity of the approximate velocity profile and corresponding radiation impedance calculation was assessed using finite element simulations for a variety of membrane aspect ratios and bias voltages. Our method was evaluated for rectangular radiators with width:length ratios from 1:1 up to 1:25. At all aspect ratios, the radiation resistance was closely modeled. However, when calculating the radiation reactance, our initial approach was only accurate for low aspect ratios. This motivated us to consider an alternative shape model for high aspect ratios, which was more accurate when compared with FEM. To facilitate the development of future rectangular CMUTs, we provide a MATLAB script that quickly calculates radiation impedance using both methods.

The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective.

Leptin resistance is induced via leptin signaling blockade by chronic overstimulation of the leptin receptor and intracellular signaling defect or increased hypothalamic inflammation and suppressor of cytokine signaling (SOCS)-3 expression. High-fat diet triggers leptin resistance induced by at least two independent causes: first, the limited ability of peripheral leptin to activate hypothalamic signaling transducers and activators of transcription (STAT) signaling and secondly a signaling defect in leptin-responsive hypothalamic neurons. Central leptin resistance is dependent on decreased leptin transport efficiency across the blood brain barrier (BBB) rather than hypothalamic leptin insensitivity. Since the hypothalamic phosphorylated STAT3 (pSTAT3) represents a sensitive and specific readout of leptin receptor-B signaling, the assessment of pSTAT3 levels is the gold standard. Hypertriglyceridemia is one of important factors to inhibit the transport of leptin across BBB in obesity. Mismatch between high leptin and the amount of leptin receptor expression in obesity triggers brain leptin resistance via increasing hypothalamic inflammation and SOCS-3 expression. Therapeutic strategies that regulate the passage of leptin to the brain include the development of modifications in the structure of leptin analogues as well as the synthesis of new leptin receptor agonists with increased BBB permeability. In the hyperleptinemic state, polyethylene glycol (PEG)-modified leptin is unable to pass through the BBB. Peripheral histone deacetylase (HDAC) 6 inhibitor, tubastatin, and metformin increase central leptin sensitization. While add-on therapy with anagliptin, metformin and miglitol reduce leptin concentrations, the use of long-acting leptin analogs, and exendin-4 lead to the recovery of leptin sensitivity. Contouring surgery with fat removal, and bariatric surgery independently of the type of surgery performed provide significant improvement in leptin concentrations. Although approaches to correcting leptin resistance have shown some success, no clinically effective application has been developed to date. Due to the impairment of central and peripheral leptin signaling, as well as the extensive integration of leptin-sensitive metabolic pathways with other neurons, the effectiveness of methods used to eliminate leptin resistance is extremely limited.

IGFBP2 Functions as an Endogenous Protector against Hepatic Steatosis via Suppression of the EGFR-STAT3 Pathway.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. APPROACH & RESULTS: By using Robust rank aggregation method to integrate all public datasets of human NAFLD transcriptome, the present study identified IGFBP2 (Insulin-like growth factor binding protein 2) being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. CONCLUSIONS: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

Effect of electromagnetic middle-ear implant simulating sites on the stapes spatial motion: A finite element analysis.

The electromagnetic middle-ear implant (MEI) is a new type of hearing device for addressing sensorineural and mixed hearing loss. The hearing compensation effect of the MEI varies depending on the transducer stimulation sites. This paper investigates the impact of transducer stimulation sites on MEI performance by analyzing stapes spatial motion. Firstly, we constructed a human-ear finite element model based on micro-CT scanning and inverse molding techniques. This model was validated by comparing its predictions of stapes spatial motion and cochlear response with experimental data. Then, stimulation force was applied at four common sites: umbo, incus body, incus long process and stapes to simulate the electromagnetic transducer. Results show that at low and middle frequencies, stapes-stimulating and incus-long-process-stimulating produce similar spatial motion to normal hearing; at high frequencies, incus-body-stimulating produces similar results to normal hearing. The equivalent sound pressure level generated by the stapes piston motion is less sensitive to the stimulation direction than that deduced by the stapes rocking motion.

Zinc finger protein 263 promotes colorectal cancer cell progression by activating STAT3 and enhancing chemoradiotherapy resistance.

Zinc finger protein 263 (ZNF263) is frequently upregulated in various tumor types; however, its function and regulatory mechanism in colorectal cancer (CRC) have not yet been elucidated. In this study, the expression of ZNF263 was systematically examined using data from The Cancer Genome Atlas database and samples from patients with CRC. The results indicated that high expression of ZNF263 in CRC tissues is significantly associated with tumor grade, lymph node metastasis and disant metastasis. Additionally, overexpression of ZNF263 significantly promoted the proliferation, invasion, migration, and epithelial-mesenchymal transition of CRC cells, while also increasing signal transducer and activator of transcription 3 (STAT3) expression and mRNA stability. Conversely, knockdown of ZNF263 inhibited the malignant behavior of CRC cells and decreased STAT3 expression and mRNA stability. Further mechanism studies using chromatin immunoprecipitation (CHIP) and luciferase assays verified that ZNF263 directly binds to the STAT3 promoter. Rescue experiments demonstrated that the knockdown or overexpression of STAT3 could significantly reverse the effects of ZNF263 on CRC cells. Additionally, our study found that overexpression of ZNF263 enhanced the resistance of CRC cells to the chemoradiotherapy. In summary, this study not only elucidated the significant role of ZNF263 in CRC but also proposed novel approaches and methodologies for the diagnosis and treatment of this malignancy.

Acoustic Transmission Measurements for Extracting the Mechanical Properties of Complex 3D MEMS Transducers.

Recent publications on acoustic MEMS transducers present a new three-dimensional folded diaphragm that utilizes buried in-plane vibrating structures to increase the active area from a small chip volume. Characterization of the mechanical properties plays a key role in the development of new MEMS transducers, whereby established measurement methods are usually tailored to structures close to the sample surface. In order to access the lateral vibrations, extensive and destructive sample preparation is required. This work presents a new passive measurement technique that combines acoustic transmission measurements and lumped-element modelling. For diaphragms of different lengths, compliances between 0.08 × 10-15 and 1.04 × 10-15 m3/Pa are determined without using destructive or complex preparations. In particular, for lengths above 1000 µm, the results differ from numerical simulations by only 4% or less.

Design, Fabrication, and Characterization of Capacitive Micromachined Ultrasonic Transducers for Transcranial, Multifocus Neurostimulation.

In a recent study using 3-D fullwave simulations, it was shown for a nonhuman primate model that a helmet-shaped 3D array of 128 transducer elements can be assembled for neurostimulation in an optimized configuration with the accommodation of an imaging aperture. Considering all acoustic losses, according to this study, for a nonhuman primate skull, the assembly of the proposed transducers was projected to produce sufficient focusing gain in two different focal positions at deep and shallow brain regions, thus providing sufficient acoustic intensity at these distinct focal points for neural stimulation. This array also has the ability to focus on multiple additional brain regions. In the work presented here, we designed and fabricated a single 15 mm diameter capacitive micromachined ultrasonic transducer (CMUT) element operating at 800 kHz central frequency with a 480 kHz 3 dB bandwidth, capable of producing a 190 kPa peak negative pressure (PNP) on the surface. The corresponding projected transcranial spatial peak pulse average intensity (ISPPA) was 28 Wcm-2, and the mechanical index (MI) value was 1.1 for an array of 128 of these elements.

Fine-Tuning of Optical Resonance Wavelength of Surface-Micromachined Optical Ultrasound Transducer Arrays for Single-Wavelength Light Source Readout.

This article reports the fine-tuning of the optical resonance wavelength (ORW) of surface-micromachined optical ultrasound transducer (SMOUT) arrays to enable ultrasound data readout with non-tunable interrogation light sources for photoacoustic computed tomography (PACT). Permanent ORW tuning is achieved by material deposition onto or subtraction from the top diaphragm of each element with sub-nanometer resolution. For demonstration, a SMOUT array is first fabricated, and its ORW is tuned for readout with an 808 nm laser diode (LD). Experiments are conducted to characterize the optical and acoustic performances of the elements within the center region of the SMOUT array. Two-dimensional and three-dimensional PACT (photoacoustic computed tomography) is also performed to evaluate the imaging performance of the ORW-tuned SMOUT array. The results show that the ORW tuning does not degrade the optical, acoustic, and overall imaging performances of the SMOUT elements. As a result, the fine-tuning method enables new SMOUT-based PACT systems that are low cost, compact, powerful, and even higher speed, with parallel readout capability.

A Proposed Non-Destructive Method Based on Sphere Launching and Piezoelectric Diaphragm.

This work presents the study of a reproducible acoustic emission method based on the launching of a metallic sphere and low-cost piezoelectric diaphragm. For this purpose, tests were first conducted on a carbon fiber-reinforced polymer structure, and then on an aluminum structure for comparative analysis. The pencil-lead break (PLB) tests were also conducted for comparisons with the proposed method. Different launching heights and elastic deformations of the structures were investigated. The results show higher repeatability for the sphere impact method, as the PLB is more affected by human inaccuracy, and it was also effective in damage detection.

Longitudinal-Torsional Frequency Coupling Design of Novel Ultrasonic Horns for Giant Magnetostrictive Transducers.

The use of advanced brittle composites in engineering systems has necessitated robotic rotary ultrasonic machining to attain high precision with minimal machining defects such as delamination, burrs, and cracks. Longitudinal-torsional coupled (LTC) vibrations are created by introducing helical slots to a horn's profile to enhance the quality of ultrasonic machining. In this investigative research, modified ultrasonic horns were designed for a giant magnetostrictive transducer by generating helical slots in catenoidal and cubic polynomial profiles to attain a high amplitude ratio (TA/LA) and low stress concentrations. Novel ultrasonic horns with a giant magnetostrictive transducer were modelled to compute impedances and harmonic excitation responses. A structural dynamic analysis was conducted to investigate the effect of the location, width, depth and angle of helical slots on the Eigenfrequencies, torsional vibration amplitude, longitudinal vibration amplitude, stresses and amplitude ratio in novel LTC ultrasonic horns for different materials using the finite element method (FEM) based on the block Lanczos and full-solution methods. The newly designed horns achieved a higher amplitude ratio and lower stresses in comparison to the Bezier and industrial stepped LTC horns with the same length, end diameters and operating conditions. The novel cubic polynomial LTC ultrasonic horn was found superior to its catenoidal counterpart as a result of an 8.45% higher amplitude ratio. However, the catenoidal LTC ultrasonic horn exhibited 1.87% lower stress levels. The position of the helical slots was found to have the most significant influence on the vibration characteristics of LTC ultrasonic horns followed by the width, depth and angle. This high amplitude ratio will contribute to the improved vibration characteristics that will help realize good surface morphology when machining advanced materials.

Highly selective detection of breast cancer cells mediated by multi-aptamer and dye-loaded mesoporous silica nanoparticles.

Multi-aptamer recognition of breast cancer cells (MCF-7) is utilized to achieve high specificity. The method comprises two parts, aptamer-functionalized mesoporous silica nanoparticles (MSNs) loaded with dissimilar dyes (thymolphthalein or curcumin) as signal transducers and aptamer-modified magnetic beads (MBs) as capture agents, which worked together to detect MCF-7 cells sensitively and accurately. The results indicated that the aptasensor has a linear detection range of 100 to 4000 cells and a detection threshold of 10 cells/mL. The method had been successfully employed to detect breast cancer cells in real blood samples to distinguish between breast cancer patients and healthy individuals. In conclusion, the development of the multi-aptamer-based colorimetric sensor offered a novel method for the highly selective detection of MCF-7 cells, contributing to the accurate identification of breast cancer.

Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway.

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

IL-21 drives skin and lung inflammation and fibrosis in a model for systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc. METHODS: We assessed the expression levels of fibrosis-related genes in human dermal fibroblasts exposed to IL-21 and TGF beta. We also induced SSc in wild-type C57BL/6 mice and IL-21 knockout (KO) mice with a C57BL/6 background using bleomycin (Bleomycin). Histological analyses were conducted on skin and lung tissues from these mice. The distribution and expression levels of fibrosis-related proteins in the tissues were examined via immunohistochemistry and quantitative real-time PCR. Furthermore, we measured the frequency of Th1, Th2, and Th17 cells among splenocytes through flow cytometry. RESULTS: IL-21 activation led to STAT3 phosphorylation more than TGF beta in dermal fibroblasts. In IL-21 KO mice with BLM-induced SSc, skin thickness and lung fibrosis were reduced. The absence of IL-21 in these mice resulted in suppressed expression of fibrosis-related genes, including Col1a1, Col1a2, Col3a1, CTGF, α-SMA, STAT3, and TGFß, in the skin and lungs. It also led to a decreased frequency of Th1, Th2, and Th17 cells, as well as a lower Th17/Treg ratio among splenocytes, factors known to contribute to the development of SSc. CONCLUSIONS: IL-21 contributes to the development of SSc by promoting the expression of fibrosis-related genes and modulating the levels of CD4+ T cells.

The Atypical Dual Specificity Phosphatase DUSP15 Regulates Jak1-Mediated STAT3 Activation.

The signal transducer and activator of transcription 3 (STAT3) protein is a key regulator of cell differentiation, proliferation, and survival in hematopoiesis, immune responses, and other biological systems. STAT3 transcriptional activity is strictly regulated through various mechanisms, such as phosphorylation and dephosphorylation. In this study, we attempted to identify novel phosphatases which regulate STAT3 activity in response to cytokine stimulations. To this end, leukemia inhibitory factor (LIF)/STAT3 dependent phosphatase induction was evaluated in the mouse hepatoma cell line Hepa1-6. After LIF stimulation, the expression of several atypical dual specific phosphatases (aDUSPs) was upregulated in Hepa1-6 cells. Among the LIF-induced aDUSPs, we focused on DUSP15 and clarified its functions in LIF/STAT3 signaling using RNA interference. DUSP15 knockdown decreased LIF-induced Socs3 mRNA expression and STAT3 translocation. Furthermore, loss of DUSP15 reduced the phosphorylation of STAT3 at Tyr705 and Janus family tyrosine kinase 1 (Jak1) at Tyr1034/1035 in response to LIF. The interaction between Jak1 and DUSP15 was observed in LIF-stimulated Hepa1-6 cells. We also demonstrated the suppression of granulocyte colony-stimulating factor (G-CSF)-mediated gp130/STAT3-dependent cell growth of Ba/F-G133 cells via DUSP15 knockdown. Therefore, DUSP15 functions as a positive feedback regulator in the Jak1/STAT3 signaling cascade.