Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key mol...Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.展开更多
To study the characteristics of the 5-prismatic–spherical–spherical(PSS)/universal–prismatic–universal(UPU)parallel mechanism with elastically active branched chains,the dynamics modeling and solutions of the para...To study the characteristics of the 5-prismatic–spherical–spherical(PSS)/universal–prismatic–universal(UPU)parallel mechanism with elastically active branched chains,the dynamics modeling and solutions of the parallel mechanism were investigated.First,the active branched chains and screw sliders were considered as spatial beam elements and plane beam element models,respectively,and the dynamic equations of each element model were derived using the Lagrange method.Second,the equations of the 5-PSS/UPU parallel mechanism were obtained according to the kinematic coupling relationship between the active branched chains and moving platform.Finally,based on the parallel mechanism dynamic equations,the natural frequency distribution of the 5-PSS/UPU parallel mechanism in the working space and elastic displacement of the moving platform were obtained.The results show that the natural frequency of the 5-PSS/UPU parallel mechanism under a given motion situation is greater than its operating frequency.The maximum position error is -0.096 mm in direction Y,and the maximum orientation error is -0.29°around the X-axis.The study provides important information for analyzing the dynamic performance,dynamic optimization design,and dynamic control of the 5-PSS/UPU parallel mechanism with elastically active branched chains.展开更多
Cold-inducible RNA-binding protein （CIRP） is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purp...Cold-inducible RNA-binding protein （CIRP） is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purpose of this study was to investigate the functions of CIRP in the testes. We employed RNAi technique to knock down the expression of CIRP in the testes, and performed haematoxylin and eosin staining to evaluate morphological changes following knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal transferase-mediated dUTP nick end labelling （TUNEL） assay, and mitogen-activated protein kinase （MAPK） signalling pathways were investigated by Western blotting to determine the possible mechanism of apoptosis. We found that using siRNA is a feasible and reliable method for knocking down gene expression in the testes. Compared to controls, the mean seminiferous tubule diameter （MSTD） and the thickness of the germ cell layers decreased following siRNA treatment, whereas the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In conclusion, we discovered that downregulation of CIRP resulted in increased germ cell apoptosis, possibly viathe activation of the p44/p42, p38 and SAPK/JNK MAPK pathways.展开更多
Fe3O4@SiO2 core–shell composite nanoparticles were successfully prepared by a one-pot process. Tetraethyl-orthosilicate was used as a surfactant to synthesize Fe3O4@SiO2 core–shell structures from prepared Fe3O4 nan...Fe3O4@SiO2 core–shell composite nanoparticles were successfully prepared by a one-pot process. Tetraethyl-orthosilicate was used as a surfactant to synthesize Fe3O4@SiO2 core–shell structures from prepared Fe3O4 nanoparticles. The properties of the Fe3O4 and Fe3O4@SiO2 composite nanoparticles were studied by X-ray diffraction, transmission electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. The prepared Fe3O4 particles were approximately 12 nm in size, and the thickness of the SiO2 coating was approximately 4 nm. The magnetic properties were studied by vibrating sample magnetometry. The results show that the maximum saturation magnetization of the Fe3O4@SiO2 powder（34.85 A·m^2·kg^–1） was markedly lower than that of the Fe3O4 powder（79.55 A·m^2·kg^–1）, which demonstrates that Fe3O4 was successfully wrapped by SiO2. The Fe3O4@SiO2 composite nanoparticles have broad prospects in biomedical applications; thus, our next study will apply them in magnetic resonance imaging.展开更多
Levels in the neutron-rich ^(104)Mo nucleus have been investigated by observing promptγ-rays from the spontaneous fission of 252Cf with the Gammasphere detector array.The ground-state band,the one-phonon and the two-...Levels in the neutron-rich ^(104)Mo nucleus have been investigated by observing promptγ-rays from the spontaneous fission of 252Cf with the Gammasphere detector array.The ground-state band,the one-phonon and the two-phononγ-vibrational bands as well as a quasiparticle band have been confirmed and expanded with spin up to 14ħ.Other two side bands probably built on new quasiparticle states are identified.The possible configurations for the quasiparticle bands are discussed.Two of the quasiparticle bands show larger moments of inertia and may have pair-free characteristics.The levels of the ground-state band,the one-phononγ-band and the two-phononγ-band calculated from a general collective model are in close agreement with the experimental data.展开更多
Accurate prediction of protein-ligand complex structures is a crucial step in structure-based drug design.Traditional molecular docking methods exhibit limitations in terms of accuracy and sampling space,while relying...Accurate prediction of protein-ligand complex structures is a crucial step in structure-based drug design.Traditional molecular docking methods exhibit limitations in terms of accuracy and sampling space,while relying on machine-learning approaches may lead to invalid conformations.In this study,we propose a novel strategy that combines molecular docking and machine learning methods.Firstly,the protein-ligand binding poses are predicted using a deep learning model.Subsequently,position-restricted docking on predicted binding poses is performed using Uni-Dock,generating physically constrained and valid binding poses.Finally,the binding poses are re-scored and ranked using machine learning scoring functions.This strategy harnesses the predictive power of machine learning and the physical constraints advantage of molecular docking.Evaluation experiments on multiple datasets demonstrate that,compared to using molecular docking or machine learning methods alone,our proposed strategy can significantly improve the success rate and accuracy of protein-ligand complex structure predictions.展开更多
基金supported by the Science and Technology Department of Hubei Province Key Project(YYXKNL2022001)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT320-004)+2 种基金the Hubei Provincial Natural Science Foundation(2021CFB453)the Science,Technology and Innovation Seed Fund of Zhongnan Hospital of Wuhan University(CXPY2020031)the Climbing Program for Medical Talents of Zhongnan Hospital of Wuhan University(PDJH202206,PDJH202208)。
文摘Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.
基金Supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LR18E050003)National Natural Science Foundation of China (Grant Nos. 51975523,51905481)+1 种基金Postdoctoral Preferred Funding Project of Zhejiang Province (Grant No. zj2019019)Open Foundation of the Key Laboratory of E&M,Ministry of Education&Zhejiang Province (Grant No. EM2019120102)
文摘To study the characteristics of the 5-prismatic–spherical–spherical(PSS)/universal–prismatic–universal(UPU)parallel mechanism with elastically active branched chains,the dynamics modeling and solutions of the parallel mechanism were investigated.First,the active branched chains and screw sliders were considered as spatial beam elements and plane beam element models,respectively,and the dynamic equations of each element model were derived using the Lagrange method.Second,the equations of the 5-PSS/UPU parallel mechanism were obtained according to the kinematic coupling relationship between the active branched chains and moving platform.Finally,based on the parallel mechanism dynamic equations,the natural frequency distribution of the 5-PSS/UPU parallel mechanism in the working space and elastic displacement of the moving platform were obtained.The results show that the natural frequency of the 5-PSS/UPU parallel mechanism under a given motion situation is greater than its operating frequency.The maximum position error is -0.096 mm in direction Y,and the maximum orientation error is -0.29°around the X-axis.The study provides important information for analyzing the dynamic performance,dynamic optimization design,and dynamic control of the 5-PSS/UPU parallel mechanism with elastically active branched chains.
文摘Cold-inducible RNA-binding protein （CIRP） is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purpose of this study was to investigate the functions of CIRP in the testes. We employed RNAi technique to knock down the expression of CIRP in the testes, and performed haematoxylin and eosin staining to evaluate morphological changes following knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal transferase-mediated dUTP nick end labelling （TUNEL） assay, and mitogen-activated protein kinase （MAPK） signalling pathways were investigated by Western blotting to determine the possible mechanism of apoptosis. We found that using siRNA is a feasible and reliable method for knocking down gene expression in the testes. Compared to controls, the mean seminiferous tubule diameter （MSTD） and the thickness of the germ cell layers decreased following siRNA treatment, whereas the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In conclusion, we discovered that downregulation of CIRP resulted in increased germ cell apoptosis, possibly viathe activation of the p44/p42, p38 and SAPK/JNK MAPK pathways.
基金the National Natural Science Foundation of China (No.51274039)the State Key Lab of Advanced Metals and Materials (No.2013-ZD05)the Guangdong Foundation of Research (No.2014B090901003)
文摘Fe3O4@SiO2 core–shell composite nanoparticles were successfully prepared by a one-pot process. Tetraethyl-orthosilicate was used as a surfactant to synthesize Fe3O4@SiO2 core–shell structures from prepared Fe3O4 nanoparticles. The properties of the Fe3O4 and Fe3O4@SiO2 composite nanoparticles were studied by X-ray diffraction, transmission electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. The prepared Fe3O4 particles were approximately 12 nm in size, and the thickness of the SiO2 coating was approximately 4 nm. The magnetic properties were studied by vibrating sample magnetometry. The results show that the maximum saturation magnetization of the Fe3O4@SiO2 powder（34.85 A·m^2·kg^–1） was markedly lower than that of the Fe3O4 powder（79.55 A·m^2·kg^–1）, which demonstrates that Fe3O4 was successfully wrapped by SiO2. The Fe3O4@SiO2 composite nanoparticles have broad prospects in biomedical applications; thus, our next study will apply them in magnetic resonance imaging.
基金Supported by the National Natural Science Foundation of China under Grant No.19975028the Science Foundation of China for Nuclear Industry under Grant No.Y7197AY509+1 种基金the Major State Basic Research Development Program of China under Contract No.G2000077400the U.S.Department of Energy under Grant No.DE-FG05-88ER40407.
文摘Levels in the neutron-rich ^(104)Mo nucleus have been investigated by observing promptγ-rays from the spontaneous fission of 252Cf with the Gammasphere detector array.The ground-state band,the one-phonon and the two-phononγ-vibrational bands as well as a quasiparticle band have been confirmed and expanded with spin up to 14ħ.Other two side bands probably built on new quasiparticle states are identified.The possible configurations for the quasiparticle bands are discussed.Two of the quasiparticle bands show larger moments of inertia and may have pair-free characteristics.The levels of the ground-state band,the one-phononγ-band and the two-phononγ-band calculated from a general collective model are in close agreement with the experimental data.
基金supported by the National Key Research and Development Program of China(2022YFA1004302)
文摘Accurate prediction of protein-ligand complex structures is a crucial step in structure-based drug design.Traditional molecular docking methods exhibit limitations in terms of accuracy and sampling space,while relying on machine-learning approaches may lead to invalid conformations.In this study,we propose a novel strategy that combines molecular docking and machine learning methods.Firstly,the protein-ligand binding poses are predicted using a deep learning model.Subsequently,position-restricted docking on predicted binding poses is performed using Uni-Dock,generating physically constrained and valid binding poses.Finally,the binding poses are re-scored and ranked using machine learning scoring functions.This strategy harnesses the predictive power of machine learning and the physical constraints advantage of molecular docking.Evaluation experiments on multiple datasets demonstrate that,compared to using molecular docking or machine learning methods alone,our proposed strategy can significantly improve the success rate and accuracy of protein-ligand complex structure predictions.
