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
New light curves and photometric solutions of FP Lyn,FV CVn and V354 UMa are presented.We found that these three systems are W-subtype shallow contact binaries.In addition,it is obvious that the light curves of FP Lyn...New light curves and photometric solutions of FP Lyn,FV CVn and V354 UMa are presented.We found that these three systems are W-subtype shallow contact binaries.In addition,it is obvious that the light curves of FP Lyn and V354 UMa are asymmetric.Therefore,a hot spot was added on the primary star of FP Lyn and a dark spot was added on the secondary star of V354 UMa.At the same time,we added a third light to the photometric solution of FP Lyn for the final result.The obtained mass ratios and fill-out factors are q = 1.153 and f = 13.4% for FP Lyn,q = 1.075 and f = 4.6% for FV CVn,and q = 3.623 and f = 10.7% for V354 UMa respectively.The investigations of orbital period for these three systems indicate that the periods are variable.FP Lyn and V354 UMa were discovered to have secularly increasing components with rates of dp/dt = 4.19 ×10^-7 dyr^-1 and dp/dt = 7.70 ×10^-7 dyr^-1 respectively,which are feasibly caused by conservative mass transfer from the less massive component to the more massive component.In addition,some variable components were discovered for FV CVn,including a rate of dp/dt =-1.13 ×10^-6 dyr^-1 accompanied by a cyclic oscillation with amplitude and period of 0.0069 d and 10.65 yr respectively.The most likely explanation for the long-term decrease is angular momentum loss.The existence of an additional star is the most plausible explanation for the periodic variation.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financial support from the Universidad Nacional Aut ónoma de México (UNAM) and DGAPA (PAPIIT IN 100918)supported by the National Natural Science Foundation of China (NSFC) (No. 11703016)+3 种基金by the Joint Research Fund in Astronomy (No. U1431105)by the Natural Science Foundation of Shandong Province (No. ZR2014AQ019)by the Young Scholars Program of Shandong University, Weihai (No. 20820171006)by the Open Research Program of Key Laboratory for the Structure and Evolution of Celestial Objects (No. OP201704)
文摘New light curves and photometric solutions of FP Lyn,FV CVn and V354 UMa are presented.We found that these three systems are W-subtype shallow contact binaries.In addition,it is obvious that the light curves of FP Lyn and V354 UMa are asymmetric.Therefore,a hot spot was added on the primary star of FP Lyn and a dark spot was added on the secondary star of V354 UMa.At the same time,we added a third light to the photometric solution of FP Lyn for the final result.The obtained mass ratios and fill-out factors are q = 1.153 and f = 13.4% for FP Lyn,q = 1.075 and f = 4.6% for FV CVn,and q = 3.623 and f = 10.7% for V354 UMa respectively.The investigations of orbital period for these three systems indicate that the periods are variable.FP Lyn and V354 UMa were discovered to have secularly increasing components with rates of dp/dt = 4.19 ×10^-7 dyr^-1 and dp/dt = 7.70 ×10^-7 dyr^-1 respectively,which are feasibly caused by conservative mass transfer from the less massive component to the more massive component.In addition,some variable components were discovered for FV CVn,including a rate of dp/dt =-1.13 ×10^-6 dyr^-1 accompanied by a cyclic oscillation with amplitude and period of 0.0069 d and 10.65 yr respectively.The most likely explanation for the long-term decrease is angular momentum loss.The existence of an additional star is the most plausible explanation for the periodic variation.
