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
We present the first photometric and orbital period investigations for a neglected totally eclipsing contact binary IP Lyn.The photometric solutions derived from both ground-based and several surveys'observations ...We present the first photometric and orbital period investigations for a neglected totally eclipsing contact binary IP Lyn.The photometric solutions derived from both ground-based and several surveys'observations suggest that it is a shallow contact binary with an extremely low mass ratio of 0.055.The weak asymmetry observed in our multiple band light curves can be interpreted as a result of an active cool spot on the primary.The absolute physical parameters were determined with the Gaia-distance-based method and checked by an empirical relation.Combining the eclipse timings collected from the literature and those derived from our and variable surveys'observations,we find that IP Lyn has been undergoing a secular orbital period increase for the past two decades,implying a mass transfer from the less massive secondary to the primary.By comparing the current parameters with the critical instability ones,we infer that IP Lyn is currently stable in spite of its relatively low mass ratio and orbital angular momentum.Finally,from a catalog of 117 extremely low mass ratio contact binaries,we find that their orbital angular momenta are significantly lower than those of the contact binaries with a relatively high mass ratio,suggesting they should be at the late evolutionary stage of a contact binary.展开更多
We present 145 times of light maximum for high amplitude δ Scuti star BO Lyn based on several sky surveys（CRTS,DASCH,NSVS,OMC and Super WASP）and our photometric observations.Combining with the data in literature,a ...We present 145 times of light maximum for high amplitude δ Scuti star BO Lyn based on several sky surveys（CRTS,DASCH,NSVS,OMC and Super WASP）and our photometric observations.Combining with the data in literature,a total of 179 times of light maximum are used to analyze the O-C diagram of BO Lyn.We find that it can be described by an upward parabolic component and a periodic variation with a period of 34.5±0.1 yr.The latter could be caused by the light travel time effect as a result of an additional companion orbiting in a highly elliptical orbit（e=0.64±0.03）.Our study indicates that the companion’s luminosity cannot be ignored,and it should be a late A-type main-sequence star.The long-term period change of BO Lyn is also detected,and its value,1.52±0.26×10^（-3）d Myr^（-1）,is consistent with evolutionary models.We suggest that more spectroscopic and photometric observations are needed in the future to confirm the nature of the BO Lyn system.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 the Joint Research Funds in Astronomy under a cooperative agreement between the National Natural Science Foundation of China(NSFC)and the Chinese Academy of Sciences(Nos.U1931115 and U2031114)Scientific Research Fund of Hunan Provincial Education Department grant No.22A0099+1 种基金the support of the staff of the Xinglong 85 cm telescopepartially supported by the Open Project Program of the Key Laboratory of Optical Astronomy,National Astronomical Observatories,Chinese Academy of Sciences。
文摘We present the first photometric and orbital period investigations for a neglected totally eclipsing contact binary IP Lyn.The photometric solutions derived from both ground-based and several surveys'observations suggest that it is a shallow contact binary with an extremely low mass ratio of 0.055.The weak asymmetry observed in our multiple band light curves can be interpreted as a result of an active cool spot on the primary.The absolute physical parameters were determined with the Gaia-distance-based method and checked by an empirical relation.Combining the eclipse timings collected from the literature and those derived from our and variable surveys'observations,we find that IP Lyn has been undergoing a secular orbital period increase for the past two decades,implying a mass transfer from the less massive secondary to the primary.By comparing the current parameters with the critical instability ones,we infer that IP Lyn is currently stable in spite of its relatively low mass ratio and orbital angular momentum.Finally,from a catalog of 117 extremely low mass ratio contact binaries,we find that their orbital angular momenta are significantly lower than those of the contact binaries with a relatively high mass ratio,suggesting they should be at the late evolutionary stage of a contact binary.
基金The DASCH project at Harvard is grateful for partial support from NSF grants AST-0407380,AST0909073 and AST-1313370partly supported by the West Light Foundation of Chinese Academy of Sciences+2 种基金the National Natural Science Foundation of China(Nos.11325315 and 11573063)the Yunnan Natural Science Foundation(Nos.2013FB084,2014FB187 and 2017FA001)the Strategic Priority Research Program “The Emergence of Cosmological Structures” of the Chinese Academy of Sciences(Grant No.XDB09010202)
文摘We present 145 times of light maximum for high amplitude δ Scuti star BO Lyn based on several sky surveys（CRTS,DASCH,NSVS,OMC and Super WASP）and our photometric observations.Combining with the data in literature,a total of 179 times of light maximum are used to analyze the O-C diagram of BO Lyn.We find that it can be described by an upward parabolic component and a periodic variation with a period of 34.5±0.1 yr.The latter could be caused by the light travel time effect as a result of an additional companion orbiting in a highly elliptical orbit（e=0.64±0.03）.Our study indicates that the companion’s luminosity cannot be ignored,and it should be a late A-type main-sequence star.The long-term period change of BO Lyn is also detected,and its value,1.52±0.26×10^（-3）d Myr^（-1）,is consistent with evolutionary models.We suggest that more spectroscopic and photometric observations are needed in the future to confirm the nature of the BO Lyn system.
