Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Photoacoustic microscopy based on transparent piezoelectric ultrasound transducers

Photoacoustic microscopy(PAM),due to its deep penetration depth and high contrast,is playing an increasingly important role in biomedical imaging.PAM imaging systems equipped with conventional ultrasound transducers have demonstrated excellent imaging performance.However,these opaque ultrasonic transducers bring some constraints to the further development and application of PAM,such as complex optical path,bulky size,and difficult to integrate with other modalities.To overcome these problems,ultrasonic transducers with high optical transparency have appeared.At present,transparent ultrasonic transducers are divided into optical-based and acoustic-based sensors.In this paper,we mainly describe the acoustic-based piezoelectric transparent transducers in detail,of which the research advances in PAM applications are reviewed.In addition,the potential challenges and developments of transparent transducers in PAM are also demonstrated.

传感器在生物医学领域研究的前沿进展--TRANSDUCERS 2023国际会议综述

2023年6月25日至6月29日,第22届国际固态传感器、执行器和微系统会议(TRANSDUCERS 2023)在日本京都召开,来自世界各地的专家学者济济一堂,分享在传感器与执行器等领域的最新研究成果。本文从可穿戴生物传感器、生物传感器后端电路和传感器在生物医学领域的应用等3个角度,详细介绍并阐述本次会议上的前沿研究成果,并对相关研究成果的研究意义与未来展望给出了总结。

Helical particle manipulation based on power-exponent-phase acoustic vortices generated by a sector transducer array

The characteristics of traditional acoustic vortices(AVs) were verified by the cross-sectional axisymmetric pressure distributions with perfect phase spirals around the center pressure null. In order to generate a non-axisymmetric pressure distribution, the concept of power-exponent-phase was first introduced into the formation of AV beams, named “powerexponent-phase acoustic vortices(PAVs)” in this paper. Based on a ring-array of sector transducers, the helical distribution of the low-pressure valley in cross-sections of PAVs, which enables particles to move from a distant position to the center low-potential well along a certain spiral passageway, was proved theoretically. The particle manipulation behavior for PAVs with a power order of 2 is numerically modeled and experimentally confirmed. The results show that PAVs with a nonaxisymmetric spiral pressure distribution can be used to realize the directional transport of particles in an enlarged scope,suggesting prospective application potential in biomedical engineering.

Inverse design and realization of an optical cavity-based displacement transducer with arbitrary responses

Optical cavity has long been critical for a variety of applications ranging from precise measurement to spectral analysis.A number of theories and methods have been successful in describing the optical response of a stratified optical cavity,while the inverse problem,especially the inverse design of a displacement sensitive cavity,remains a significant challenge due to the cost of computation and comprehensive performance requirements.This paper reports a novel inverse design methodology combining the characteristic matrix method,mixed-discrete variables optimization algorithm,and Monte Carlo method-based tolerance analysis.The material characteristics are indexed to enable the mixed-discrete variables optimization,which yields considerable speed and efficiency improvements.This method allows arbitrary response adjustment with technical feasibility and gives a glimpse into the analytical characterization of the optical response.Two entirely different light-displacement responses,including an asymmetric sawtooth-like response and a highly symmetric response,are dug out and experimentally achieved,which fully confirms the validity of the method.The compact Fabry-Perot cavities have a good balance between performance and feasibility,making them promising candidates for displacement transducers.More importantly,the proposed inverse design paves the way for a universal design of optical cavities,or even nanophotonic devices.

Design and analysis of longitudinal–flexural hybrid transducer for ultrasonic peen forming

Ultrasonic peen forming(UPF)is an emerging technology that exhibits great superiority in both its flexible operating modes and the deep residual stress that it produces compared with conventional plastic forming methods.Although ultrasonic transducers with longitudinal vibration have been widely studied,they have seldom been incorporated into UPF devices for machining in confined spaces.To meet the requirements of this type of machining,a sandwich-type piezoelectric transducer with coupled longitudinal-flexural vibrational modes is proposed.The basic structure of the transducer is designed to obtain large vibrational amplitudes in both modes.Experimental results obtained with a prototype device demonstrate the feasibility of the proposed transducer.The measured vibrational amplitude for the working face in the longitudinal vibrational mode is 1.0μm,and electrical matching increases this amplitude by 40%.The flexural vibration characteristics of the same prototype transducer are also tested and are found to be slightly smaller than those of longitudinal mode.The resultant working strokes of the UPF impact pins reach 1.7 mm and 1.2 mm in the longitudinal and flexural modes,respectively.The forming capability of the prototype has been evaluated via 15-min machining on standard 2024-T351 aluminum plates.After UPF,an improved surface morphology with lower surface roughness is obtained.The aluminum plate test piece has an apparent upper deformation with an arc height of 0.64 mm.The measured peak value of the compressive residual stress is around 250 MPa,appearing at a depth of 100μm.The proposed longitudinal-flexural hybrid transducer thus provides a high-performance tool for plate peen forming in confined spaces.

18β-glycyrrhetinic acid promotes gastric cancer cell autophagy and inhibits proliferation by regulating miR-328-3p/signal transducer and activator of transcription 3

BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.

Inner damage identification and residual strength assessment of a 3D printed tunnel with marble-like cementitious materials using piezoelectric transducers

Quantitative damage identification of surrounding rock is important to assess the current condition and residual strength of underground tunnels.In this work,an underground tunnel model with marble-like cementitious materials was first fabricated using the three-dimensional(3D)printing technique and then loaded to simulate its failure mode in the laboratory.Lead zirconate titanate piezoelectric(PZT)transducers were embedded in the surrounding rock around the tunnel in the process of 3D printing.A 3D monitoring network was formed to locate damage areas and evaluate damage extent during loading.Results show that as the load increased,main cracks firstly appeared above the tunnel roof and below the floor,and then they coalesced into the tunnel boundary.Finally,the tunnel model was broken into several parts.The resonant frequency and the peak of the conductance signature firstly shifted rightwards with loading due to the sealing of microcracks,and then shifted backwards after new cracks appeared.An overall increase in the root-mean-square deviation(RMSD)calculated from conductance signatures of all the PZT transducers was observed as the load(damage)increased.Damage-dependent equivalent stiffness parameters(ESPs)were calculated from the real and imaginary signatures of each PZT at different damage states.Satisfactory agreement between equivalent and experimental ESP values was achieved.Also,the relationship between the change of the ESP and the residual strength was obtained.The method paves the way for damage identification and residual strength estimation of other 3D printed structures in civil engineering.

Combined Digital Electronic Current and Voltage Transducer

A high performance current and voltage measurement system has been developed in power system. The system is composed of two parts: one current measurement element and one voltage measurement element. A Rogowski coil and a capacitive voltage divider are used respectively for the line current and voltage measurements. Active electronic components are used to modulate signal, and power supply for these components is drawn from power line via an auxiliary current transformer. Measurement signal is transmitted by optical fibers, which is resistant to electromagnetic induction and noise. With careful design and the use of digital signal processing technology, the whole system can meet 0.5% accuracy for metering and provides large dynamic range coupled with good accuracy for protective relaying use.

Diffusion-weighted magnetic resonance imaging reflects activation of signal transducer and activator of transcription 3 during focal cerebral ischemia/reperfusion

Signal transducer and activator of transcription（STAT）is a unique protein family that binds to DNA,coupled with tyrosine phosphorylation signaling pathways,acting as a transcriptional regulator to mediate a variety of biological effects.Cerebral ischemia and reperfusion can activate STATs signaling pathway,but no studies have confirmed whether STAT activation can be verified by diffusion-weighted magnetic resonance imaging（DWI）in rats after cerebral ischemia/reperfusion.Here,we established a rat model of focal cerebral ischemia injury using the modified Longa method.DWI revealed hyperintensity in parts of the left hemisphere before reperfusion and a low apparent diffusion coefficient.STAT3 protein expression showed no significant change after reperfusion,but phosphorylated STAT3 expression began to increase after 30 minutes of reperfusion and peaked at 24 hours.Pearson correlation analysis showed that STAT3 activation was correlated positively with the relative apparent diffusion coefficient and negatively with the DWI abnormal signal area.These results indicate that DWI is a reliable representation of the infarct area and reflects STAT phosphorylation in rat brain following focal cerebral ischemia/reperfusion.

Genetic Algorithm-Based Estimation of Nonlinear Transducer

This paper describes an innovative, genetic algorithm based inverse model of nonlinear transducer. In the inverse modeling, using a genetic algorithm, the unknown coefficients of the model are estimated accurately. The simulation results indicate that this technique provides greater flexibility and suitability than the existing methods. It is very easy to modify the nonlinear transducer on line. Thus the method improves the transducer's accuracy. With the help of genetic algorithm (GA), the model coefficients' training are less likely to be trapped in local minima than traditional gradient based search algorithms.

Regulation and function of signal transducer and activator of transcription 3

Signal transducer and activator of transcription 3(STAT3), a member of the STAT family, is a key regulator of many physiological and pathological processes. Significant progress has been made in understanding the transcriptional control, posttranslational modification, cellular localization and functional regulation of STAT3. STAT3 can translocate into the nucleus and bind to specific promoter sequences, thereby exerting transcriptional regulation. Recent studies have shown that STAT3 can also translocate into mitochondria, participating in aerobic respiration and apoptosis. In addition, STAT3 plays an important role in inflammation and tumorigenesis by regulating cell proliferation, differentiation and metabolism. Conditional knockout mouse models make it possible to study the physiological function of STAT3 in specific tissues and organs. This review summarizes the latest advances in the understanding of the expression, regulation and function of STAT3 in physiological and tumorigenic processes.

Modeling and finite element analysis of transduction process of electromagnetic acoustic transducers for nonferromagnetic metal material testing

Facing the problems lack of considering the non-uniform distribution of the static bias magnetic field and computing the panicle displacements in the simulation model of electromagnetic acoustic transducer （EMAT）, a multi-field coupled model was established and the finite element method （FEM） was presented to calculate the entire transduction process. The multi-field coupled model included the static magnetic field, pulsed eddy current field and mechanical field. The FEM equations of the three fields were derived by Garlerkin FEM method. Thus, the entire transduction process of the EMAT was calculated through sequentially coupling the three fields. The transduction process of a Lamb wave EMAT was calculated according to the present model and method. The results show that, by the present method, it is valid to calculate the particle displacement under the given excitation signal and non-uniformly distributed static magnetic field. Calculation error will be brought about if the non-uniform distribution of the static bias magnetic field is neglected.

Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions

BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.

OPTIMAL DESIGN OF A 6-AXIS FORCE TRANSDUCER BASED ON STEWART PLATFORM RELATED TO SENSITIVITY ISOTROPY

The design method of a 6-axis force robot's transducer based on the Stewartplatform is detailed. For this purpose, the sensitivity isotropy evaluation criteria of thetransducer are defined, and by the aid of computer, the relationships between the criteria and theparameters of all the transducers based on the Stewart platform are investigated within thegeometric model of the solution space, which can provide the theoretical background for the optimalconstruction design of the 6-axis force transducer related to the sensitivity isotropy.

Downregulation of signal transducer and activator of transcription 3 by sorafenib:A novel mechanism for hepatocellular carcinoma therapy

Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search for and identify novel and potent therapeutic targets to improve patient outcomes.Sorafenib is the first and only approved targeted therapy for the treatment of hepatocellular carcinoma.Besides functioning as a multiple tyrosine kinase,sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3(STAT3) signaling in hepatocellular carcinoma cells.STAT3 is a key regulator of inflammation,cell survival,and tumorigenesis of liver cells,and the high percentage of hepatocellular carcinoma cells with constitutively active STAT3 justifies targeting it for the development of novel therapeutics.Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a conformational change in and releasing the autoinhibition of Src homology region 2 domaincontaining phosphatase-1.This phosphatase negatively regulates STAT3 activity,which leads to the subsequent apoptosis of cancer cells.The novel anti-cancer property of sorafenib will be discussed in this review,not only adding information regarding its mechanism of action but also providing an innovative approach for the development of cancer therapeutics in the future.

Ultrasound Imaging of Pipeline Crack Based on Composite Transducer Array

Cracks, especially small cracks are di cult to be detected in oil and gas transportation pipelines buried underground or covered with layers of material by using the traditional ultrasonic inspection techniques. Therefore, a new com?posite ultrasonic transducer array with three acoustic beam incidence modes is developed. The space model of the array is also established to obtain the defect reflection point location. And the crack ultrasound image is thus formed through a series of small cubical elements expanded around the point locations by using the projection of binariza?tion values extracted from the received ultrasonic echo signals. Laboratory experiments are performed on a pipeline sample with di erent types of cracks to verify the e ectiveness and performance of the proposed technique. From the image, the presence of small cracks can be clearly observed, in addition to the sizes and orientations of the cracks. The proposed technique can not only inspect common flaws, but also detect cracks with various orientations, which is helpful for defect evaluation in pipeline testing.

Excitation and Detection of Shear Horizontal Waves with Electromagnetic Acoustic Transducers for Nondestructive Testing of Plates

The fundamental shear horizontal（SH0） wave has several unique features that are attractive for long-range nondestructive testing（NDT）. By a careful design of the geometric configuration, electromagnetic acoustic transducers（EMATs） have the capability to generate a wide range of guided wave modes, such as Lamb waves and shear-horizontal（SH） waves in plates. However, the performance of EMATs is influenced by their parameters. To evaluate the performance of periodic permanent magnet（PPM） EMATs, a distributed-line-source model is developed to calculate the angular acoustic field cross-section in the far-field. Numerical analysis is conducted to investigate the performance of such EMATs with different geometric parameters, such as period and number of magnet arrays, and inner and outer coil widths. Such parameters have a great influence on the directivity of the generated SH0 waves that arises mainly in the amplitude and width of both main and side lobes. According to the numerical analysis, these parameters are optimized to obtain better directivity. Optimized PPM EMATs are designed and used for NDT of strip plates. Experimental results show that the lateral boundary of the strip plate has no perceivable influence on SHO-wave propagation, thus validating their used in NDT. The proposed model predicts the radiation pattern ofPPM EMATs, and can be used for their parameter optimization.

Simulation of thermal field induced by concave spherical transducer in multi-layer media

High intensity focused ultrasound(HIFU)therapy is an effective method in clinical treatment of tumors,in order to explore the bio-heat conduction mechanism of in multi-layer media by concave spherical transducer,temperature field induced by this kind of transducer in multi-layer media will be simulated through solving Pennes equation with finite difference method,and the influence of initial sound pressure,absorption coefficient,and thickness of different layers of biological tissue as well as thermal conductivity parameter on sound focus and temperature distribution will be analyzed,respectively.The results show that the temperature in focus area increases faster while the initial sound pressure and thermal conductivity increase.The absorption coefficient is smaller,the ultrasound intensity in the focus area is bigger,and the size of the focus area is increasing.When the thicknesses of different layers of tissue change,the focus position changes slightly,but the sound intensity of the focus area will change obviously.The temperature in focus area will rise quickly before reaching a threshold,and then the temperature will keep in the threshold range.

Design of a hexagonal air-coupled capacitive micromachined ultrasonic transducer for air parametric array

An air parametric array can generate a highly directional beam of audible sound in air,which has a wide range of applications in targeted audio delivery.Capacitive micromachined ultrasonic transducer(CMUTs)have great potential for air-coupled applications,mainly because of their low acoustic impedance.In this study,an air-coupled CMUT array is designed as an air parametric array.A hexagonal array is proposed to improve the directivity of the sound generated.A finite element model of the CMUT is established in COMSOL software to facilitate the choice of appropriate structural parameters of the CMUT cell.The CMUT array is then fabricated by a wafer bonding process with high consistency.The performances of the CMUT are tested to verify the accuracy of the finite element analysis.By optimizing the component parameters of the bias-T circuit used for driving the CMUT,DC and AC voltages can be effectively applied to the top and bottom electrodes of the CMUT to provide efficient ultrasound transmission.Finally,the prepared hexagonal array is successfully used to conduct preliminary experiments on its application as an air parametric array.