Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squ...Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.展开更多
Superconducting circuit quantum electrodynamics(QED)architecture composed of superconducting qubit and resonator is a powerful platform for exploring quantum physics and quantum information processing.By employing tec...Superconducting circuit quantum electrodynamics(QED)architecture composed of superconducting qubit and resonator is a powerful platform for exploring quantum physics and quantum information processing.By employing techniques developed for superconducting quantum computing,we experimentally investigate phase-sensitive Landau-Zener-Stückelberg(LZS)interference phenomena in a circuit QED.Our experiments cover an extensive range of LZS transition parameters and demonstrate the LZS induced Rabi-like oscillation as well as phase-dependent steady-state population.展开更多
This paper presents the development of lateral depletion-mode n-channel 4 H-SiC junction field-effect transistors(LJFETs)using double-mesa process toward high-temperature integrated circuit(IC)applications.At room tem...This paper presents the development of lateral depletion-mode n-channel 4 H-SiC junction field-effect transistors(LJFETs)using double-mesa process toward high-temperature integrated circuit(IC)applications.At room temperature,the fabricated LJFETs show a drain-to-source saturation current of 23.03μA/μm,which corresponds to a current density of 7678 A/cm^(2).The gate-to-source parasitic resistance of 17.56 kΩ·μm is reduced to contribute only 13.49%of the on-resistance of 130.15 kΩ·μm,which helps to improve the transconductance up to 8.61μS/μm.High temperature characteristics of LJFETs were performed from room temperature to 400℃.At temperatures up to 400℃in air,it is observed that the fabricated LJFETs still show normally-on operating characteristics.The drain-to-source saturation current,transconductance and intrinsic gain at 400℃are 7.47μA/μm,2.35μS/μm and 41.35,respectively.These results show significant improvement over state-of-the-art and make them attractive for high-temperature IC applications.展开更多
基金supported by the National Natural Science Foundation of China (82103508, 81871866, 82173252, 81672996)the Natural Science Foundation of Shaanxi Province (2022JQ?862)。
文摘Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
基金Project supported by the Key-Area Research and Development Program of Guangdong Province,China(Grant No.2018B030326001)the National Natural Science Foundation of China(Grant Nos.U1801661,11874065,and Youth Project No.11904158)+2 种基金the Guangdong Provincial Key Laboratory(Grant No.2019B121203002)the Natural Science Foundation of Hunan Province,China(Grant No.2018JJ1031)the Science,Technology and Innovation Commission of Shenzhen Municipality(Grant Nos.JCYJ20170412152620376 and YTDPT20181011104202253)。
文摘Superconducting circuit quantum electrodynamics(QED)architecture composed of superconducting qubit and resonator is a powerful platform for exploring quantum physics and quantum information processing.By employing techniques developed for superconducting quantum computing,we experimentally investigate phase-sensitive Landau-Zener-Stückelberg(LZS)interference phenomena in a circuit QED.Our experiments cover an extensive range of LZS transition parameters and demonstrate the LZS induced Rabi-like oscillation as well as phase-dependent steady-state population.
基金Project supported by the Key Research and Development Program of Shaanxi Province,China(Grant No.2020ZDLGY03-07)the National Science Foundation of China(Grant Nos.61774117 and 61774119)+4 种基金the Science Challenge Project(Grant No.TZ2018003)the National Key R&D Program of China(Grant No.2017YFB0102302)the Shaanxi Science&Technology Nova Program,China(Grant No.2019KJXX-029)the Key-Area Research and Development Program of Guang Dong Province,China(Grant No.2020B010170001)the Fundamental Research Funds for the Central Universities,China(Grant No.5012-20106205935)。
文摘This paper presents the development of lateral depletion-mode n-channel 4 H-SiC junction field-effect transistors(LJFETs)using double-mesa process toward high-temperature integrated circuit(IC)applications.At room temperature,the fabricated LJFETs show a drain-to-source saturation current of 23.03μA/μm,which corresponds to a current density of 7678 A/cm^(2).The gate-to-source parasitic resistance of 17.56 kΩ·μm is reduced to contribute only 13.49%of the on-resistance of 130.15 kΩ·μm,which helps to improve the transconductance up to 8.61μS/μm.High temperature characteristics of LJFETs were performed from room temperature to 400℃.At temperatures up to 400℃in air,it is observed that the fabricated LJFETs still show normally-on operating characteristics.The drain-to-source saturation current,transconductance and intrinsic gain at 400℃are 7.47μA/μm,2.35μS/μm and 41.35,respectively.These results show significant improvement over state-of-the-art and make them attractive for high-temperature IC applications.
