Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed ...BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.展开更多
Radar interferograms are usually influenced by factors such as atmospheric artifacts,orbital errors,and terrain errors.It is difficult to reduce the influence by using the conventional small baseline subset(SBAS)metho...Radar interferograms are usually influenced by factors such as atmospheric artifacts,orbital errors,and terrain errors.It is difficult to reduce the influence by using the conventional small baseline subset(SBAS)method when determining the deformation rate.This study uses the adjustment model with systematic parameters to improve the conventional SBAS method and employs it to determine the interseismic deformation rate of the Haiyuan fault system,providing a data reference for exploring the locking depth,strain accumulation state,and potential seismic risk assessment of different segments of the Haiyuan fault system.The results are as follows:(1)the simulation experiment verifies the feasibility and robustness of the modified SBAS method.This method can effectively reduce the influence of residual signals such as atmospheric artifacts,orbital errors and terrain errors in the interferograms.The deformation rate map can be significantly improved;(2)the deformation rate field in the radar’s Line of Sight(LOS)direction shows that there are obvious differences between the north and south sides of Haiyuan fault system,which is consistent with the characteristics of the left-lateral strike-slip movement of the Haiyuan fault system.The deformation rate field and profiles reflect the complex trends among different segments of Haiyuan fault system in detail.(3)the deformation rate of the Jingtai pull-apart basin is higher than that of the surrounding areas,possibly indicating strong regional activity,which provides a reference for studying the seismic risk of the Jingtai pull-apart basin;and(4)the interseismic deformation rate and profiles across the fault show that the middle section of the Lao Hu Shan(LHS)segment and the western and middle sections of the Haiyuan segment are locked.展开更多
Dear Editor,Lung cancer is the predominant cause of cancer-related death worldwide[1].Non-small cell lung cancer accounts for 80%-85%and small cell lung cancer(SCLC)accounts for 15%-20%of all lung cancer cases[2].Pati...Dear Editor,Lung cancer is the predominant cause of cancer-related death worldwide[1].Non-small cell lung cancer accounts for 80%-85%and small cell lung cancer(SCLC)accounts for 15%-20%of all lung cancer cases[2].Patients with SCLC,a highly aggressive and poorly differentiated malignancy,have an alarming average 5-year overall sur-vival rate of less than 10%[3].Most patients with SCLC already show clinically detectable metastases at diag-nosis and have extremely poor prognoses,even when treated with multimodality therapy[4].Before the addi-tion of atezolizumab to chemotherapy became the first-line treatment of extensive-stage SCLC,chemotherapy is the primary treatment of SCLC[5].展开更多
The control of spin electromagnetic(EM)waves is of great significance in optical communications.Although geometric metasurfaces have shown unprecedented capability to manipulate the wavefronts of spin EM waves,it is s...The control of spin electromagnetic(EM)waves is of great significance in optical communications.Although geometric metasurfaces have shown unprecedented capability to manipulate the wavefronts of spin EM waves,it is still challenging to independently manipulate each spin state and intensity distribution,which inevitably degrades metasurface-based devices for further applications.Here we propose and experimentally demonstrate an approach to designing spin-decoupled metalenses based on pure geometric phase,i.e.,geometric metasurfaces with predesigned phase modulation possessing functionalities of both convex lenses and concave lenses.Under the illumination of left-/right-handed circularly polarized(LCP or RCP)terahertz(THz)waves,these metalenses can generate transversely/longitudinally distributed RCP/LCP multiple focal points.Since the helicity-dependent multiple focal points are locked to the polarization state of incident THz waves,the relative intensity between two orthogonal components can be controlled with different weights of LCP and RCP THz waves,leading to the intensity-tunable functionality.This robust approach for simultaneously manipulating orthogonal spin states and energy distributions of spin EM waves will open a new avenue for designing multifunctional devices and integrated communication systems.展开更多
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
文摘BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.
基金supported by the National Natural Science Foundation of China(41874011,41861134009)the National Key Research and Development Program of China(2018YFC1503603)
文摘Radar interferograms are usually influenced by factors such as atmospheric artifacts,orbital errors,and terrain errors.It is difficult to reduce the influence by using the conventional small baseline subset(SBAS)method when determining the deformation rate.This study uses the adjustment model with systematic parameters to improve the conventional SBAS method and employs it to determine the interseismic deformation rate of the Haiyuan fault system,providing a data reference for exploring the locking depth,strain accumulation state,and potential seismic risk assessment of different segments of the Haiyuan fault system.The results are as follows:(1)the simulation experiment verifies the feasibility and robustness of the modified SBAS method.This method can effectively reduce the influence of residual signals such as atmospheric artifacts,orbital errors and terrain errors in the interferograms.The deformation rate map can be significantly improved;(2)the deformation rate field in the radar’s Line of Sight(LOS)direction shows that there are obvious differences between the north and south sides of Haiyuan fault system,which is consistent with the characteristics of the left-lateral strike-slip movement of the Haiyuan fault system.The deformation rate field and profiles reflect the complex trends among different segments of Haiyuan fault system in detail.(3)the deformation rate of the Jingtai pull-apart basin is higher than that of the surrounding areas,possibly indicating strong regional activity,which provides a reference for studying the seismic risk of the Jingtai pull-apart basin;and(4)the interseismic deformation rate and profiles across the fault show that the middle section of the Lao Hu Shan(LHS)segment and the western and middle sections of the Haiyuan segment are locked.
基金This study was sponsored by the Beijing Genecast Biotechnology Co.,Beijing,China.
文摘Dear Editor,Lung cancer is the predominant cause of cancer-related death worldwide[1].Non-small cell lung cancer accounts for 80%-85%and small cell lung cancer(SCLC)accounts for 15%-20%of all lung cancer cases[2].Patients with SCLC,a highly aggressive and poorly differentiated malignancy,have an alarming average 5-year overall sur-vival rate of less than 10%[3].Most patients with SCLC already show clinically detectable metastases at diag-nosis and have extremely poor prognoses,even when treated with multimodality therapy[4].Before the addi-tion of atezolizumab to chemotherapy became the first-line treatment of extensive-stage SCLC,chemotherapy is the primary treatment of SCLC[5].
基金National Key Research and Development Program of China(2017YFA0701005)National Natural Science Foundation of China(61871268,61722111)+3 种基金Natural Science Foundation of Shanghai(18ZR1425600)“Shuguang”Program of Shanghai Education Commission(19SG44)Key Project Supported by Science and Technology Commission Shanghai Municipality(YDZX20193100004960)Higher Education Discipline Innovation Project(D18014).
文摘The control of spin electromagnetic(EM)waves is of great significance in optical communications.Although geometric metasurfaces have shown unprecedented capability to manipulate the wavefronts of spin EM waves,it is still challenging to independently manipulate each spin state and intensity distribution,which inevitably degrades metasurface-based devices for further applications.Here we propose and experimentally demonstrate an approach to designing spin-decoupled metalenses based on pure geometric phase,i.e.,geometric metasurfaces with predesigned phase modulation possessing functionalities of both convex lenses and concave lenses.Under the illumination of left-/right-handed circularly polarized(LCP or RCP)terahertz(THz)waves,these metalenses can generate transversely/longitudinally distributed RCP/LCP multiple focal points.Since the helicity-dependent multiple focal points are locked to the polarization state of incident THz waves,the relative intensity between two orthogonal components can be controlled with different weights of LCP and RCP THz waves,leading to the intensity-tunable functionality.This robust approach for simultaneously manipulating orthogonal spin states and energy distributions of spin EM waves will open a new avenue for designing multifunctional devices and integrated communication systems.
