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 sign...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.展开更多
Inspection of a pipeline is essential for the safe use of such facilities. A trial sensor using an electromagnetic acoustic transducer (EMAT), which can generate the SH-mode plate wave propagating in the circumferenti...Inspection of a pipeline is essential for the safe use of such facilities. A trial sensor using an electromagnetic acoustic transducer (EMAT), which can generate the SH-mode plate wave propagating in the circumferential direction, has been developed to realize this objective. It consists of a circulating electromagnetic induction coil around the pipe and many permanent magnets arranged on the surface of the pipe in the circumferential direction. It is postulated that the intensity of the SH-mode plate wave propagating in the circumferential direction is dependent on any defects in the circumferential direction. A resonance method was then utilized to obtain a stronger received signal. As a result, it was confirmed that the resonance status can be detected. The relationship between the signal intensity and the pipe thickness was then evaluated. It was confirmed that the wall thickness of about 20% can be detected under a static condition. Finally, a moving test has been executed by using an axially traveling device manufactured by trial. The test pipes with different sizes of drilled holes were prepared. The change in the received signal intensity according to different sizes of the drilled holes was successfully detected.展开更多
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 h...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.展开更多
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...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.展开更多
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 s...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.展开更多
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 metho...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.展开更多
Pinhole corrosion is difficult to discover through conventional ultrasonic guided waves inspection,particularly for micro-sized pinholes less than 1 mm in diameter.This study proposes a new micro-sized pinhole inspect...Pinhole corrosion is difficult to discover through conventional ultrasonic guided waves inspection,particularly for micro-sized pinholes less than 1 mm in diameter.This study proposes a new micro-sized pinhole inspection method based on segmented time reversal(STR)and high-order modes cluster(HOMC)Lamb waves.First,the principle of defect echo enhancement using STR is introduced.Conventional and STR inspection experiments were conducted on aluminum plates with a thickness of 3 mm and defects with different diameters and depths.The parameters of the segment window are discussed in detail.The results indicate that the proposed method had an amplitude four times larger than of conventional ultrasonic guided waves inspection method for pinhole defect detection and could detect micro-sized pinhole defects as small as 0.5 mm in diameter and 0.5 mm in depth.Moreover,the segment window location and width(5-10 times width of the conventional excitation signal)did not affect the detection sensitivity.The combination of low-power and STR is more conducive to detection in different environments,indicating the robustness of the proposed method.Compared with conventional ultrasonic guided wave inspection methods,the proposed method can detect much smaller defect echoes usually obscured by noise that are difficult to detect with a lower excitation power and thus this study would be a good reference for pinhole defect detection.展开更多
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-GR...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.展开更多
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 m...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.展开更多
文摘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.
文摘Inspection of a pipeline is essential for the safe use of such facilities. A trial sensor using an electromagnetic acoustic transducer (EMAT), which can generate the SH-mode plate wave propagating in the circumferential direction, has been developed to realize this objective. It consists of a circulating electromagnetic induction coil around the pipe and many permanent magnets arranged on the surface of the pipe in the circumferential direction. It is postulated that the intensity of the SH-mode plate wave propagating in the circumferential direction is dependent on any defects in the circumferential direction. A resonance method was then utilized to obtain a stronger received signal. As a result, it was confirmed that the resonance status can be detected. The relationship between the signal intensity and the pipe thickness was then evaluated. It was confirmed that the wall thickness of about 20% can be detected under a static condition. Finally, a moving test has been executed by using an axially traveling device manufactured by trial. The test pipes with different sizes of drilled holes were prepared. The change in the received signal intensity according to different sizes of the drilled holes was successfully detected.
基金supported by Guangdong Province Introduction of Innovative R&D Team(2016ZT06G375)National Natural Science Foundation of China(11804059,62205070 and 11664011).
文摘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.
基金Project supported by the Natural Science Foundation of Shandong Province, China (Grant Nos. ZR2022MF336 and ZR2022MD036)。
文摘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.
基金We are grateful for financial supports from National Natural Science Foundation of China(62004166)Natural Science Foundation of Ningbo(202003N4062)+2 种基金National Postdoctoral Program for Innovative Talents(BX20200279)Natural Science Basic Research Program of Shaanxi Province(2020JQ-199)Fundamental Research Funds for the Central Universities(31020190QD027).
文摘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.
基金supported by the National Natural Science Foundation of China(Grant Nos.51975278 and 52277055)the Qing Lan Project,the Research Fund of the State Key Laboratory of Mechanics and Control of Mechanical Structures(Nanjing University of Aeronautics and Astronautics)under Grant No.MCMS-I-0321G01+2 种基金the Biomedical Engineering Fusion Laboratory of the affiliated Jiangning Hospital of Nanjing Medical University(Grant No.JNYYZXKY202217)the Postgraduate Research&Practice Innovation Program of NUAA(Grant Nos.xcxjh20220114 and xcxjh20220111)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX23_0353).
文摘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.
基金National Natural Science Foundation of China(Grant No.62071433)National Key R&D Program of China(Grant No.2022YFC3005002)。
文摘Pinhole corrosion is difficult to discover through conventional ultrasonic guided waves inspection,particularly for micro-sized pinholes less than 1 mm in diameter.This study proposes a new micro-sized pinhole inspection method based on segmented time reversal(STR)and high-order modes cluster(HOMC)Lamb waves.First,the principle of defect echo enhancement using STR is introduced.Conventional and STR inspection experiments were conducted on aluminum plates with a thickness of 3 mm and defects with different diameters and depths.The parameters of the segment window are discussed in detail.The results indicate that the proposed method had an amplitude four times larger than of conventional ultrasonic guided waves inspection method for pinhole defect detection and could detect micro-sized pinhole defects as small as 0.5 mm in diameter and 0.5 mm in depth.Moreover,the segment window location and width(5-10 times width of the conventional excitation signal)did not affect the detection sensitivity.The combination of low-power and STR is more conducive to detection in different environments,indicating the robustness of the proposed method.Compared with conventional ultrasonic guided wave inspection methods,the proposed method can detect much smaller defect echoes usually obscured by noise that are difficult to detect with a lower excitation power and thus this study would be a good reference for pinhole defect detection.
基金Ningxia Medical University Project,No. XZ2021005Ningxia Natural Science Foundation,Nos. 2022AAC03144 and 2022AAC02039National Natural Science Foundation of China,No. 82260879
文摘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.
基金The study is financially supported by the National Major Research Instrument Development Project of the National Natural Science Foundation of China(Grant No.51627812)the National Natural Science Foundation of China(Grant No.52078181)the Natural Science Foundation of Hebei Province,China(Grant No.E2019202484)。
文摘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.