Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and ...Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and spectral information from PAN and LRMS images. Following the principle of gradual advance, this paper designs a novel network that contains two main logical functions, i.e., detail enhancement and progressive fusion, to solve the problem. More specifically, the detail enhancement module attempts to produce enhanced MS results with the same spatial sizes as corresponding PAN images, which are of higher quality than directly up-sampling LRMS images.Having a better MS base(enhanced MS) and its PAN, we progressively extract information from the PAN and enhanced MS images, expecting to capture pivotal and complementary information of the two modalities for the purpose of constructing the desired HRMS. Extensive experiments together with ablation studies on widely-used datasets are provided to verify the efficacy of our design, and demonstrate its superiority over other state-of-the-art methods both quantitatively and qualitatively. Our code has been released at https://github.com/JiaYN1/PAPS.展开更多
Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapie...Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)展开更多
Objective:Bevacizumab is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor(VEGF)with clear clinical benefits.However,overall survival of some cancer types remains low owing to ...Objective:Bevacizumab is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor(VEGF)with clear clinical benefits.However,overall survival of some cancer types remains low owing to resistance to bevacizumab therapy.While resistance is commonly ascribed to tumor cell invasion induced by hypoxia-inducible factor(HIF),less attention has been paid to the potential involvement of endothelial cells(ECs)in vasculature activated by anti-angiogenic drugs.Methods:Human umbilical vein ECs(HUVECs),bEnd.3 cells,and mouse retinal microvascular ECs(MRMECs)were treated with bevacizumab under conditions of hypoxia and effects on biological behaviors,such as migration and tube formation,examined.Regulatory effects on TGFpi and CD 105(endoglin)were established via determination o f protein and mRNA levels.We further investigated whether the effects of bevacizumab could be reversed using the receptor tyrosine kinase inhibitor anlotinib.Results:Bevacizumab upregulated TGFpi as well as CD 105,a component o f the TGFP receptor complex and an angiogenesis promoter.Elevated CD 105 induced activation of Sm adl/5,the inflammatory pathway and endothelial-mesenchymal transition.The migration ability of HUVECs was enhanced by bevacizumab under hypoxia.Upregulation o f CD 105 was abrogated by anlotinib,which targets multiple receptor tyrosine kinases including VEGFR2/3,FGFR1-4,PD G FRα/β,C-Kit,and RET.Conclusions:Bevacizumab promotes migration and tube formation of HUVECs via activation of the TGFβi pathway and upregulation of CD105 expression.Anlotinib reverses the effects of bevacizumab by inhibiting the above signals.展开更多
Our study investigated effects of C-type natriuretic peptide (CNP) on atrial dynamics and hypoxia inducible factor 1 alpha (HIF-1α) activity in perfused beating rat atria, under hypoxic conditions. Hypoxia significan...Our study investigated effects of C-type natriuretic peptide (CNP) on atrial dynamics and hypoxia inducible factor 1 alpha (HIF-1α) activity in perfused beating rat atria, under hypoxic conditions. Hypoxia significantly increased the levels of HIF-1α, concomitant with decreased trial dynamics. CNP (0.1 μmol/L) further decreased atrial dynamics under hypoxia and suppressed hypoxia-induced stimulation of HIF-1α expression. An adenylylcyclase (AC) activator, forskolin (0.1 μmol/L), significantly up-regulated atrial phosphodiesterase subtype 3A (PDE 3A) protein without affecting hypoxia-induced dynamics. In the presence of forskolin, the inhibitory effects of CNP on hypoxia-induced atrial dynamics and HIF-1α levels were significantly attenuated. Forskolin also prevented hypoxia-induced downregulation of PDE3A protein. These findings suggested that CNP inhibited atrial dynamics and HIF-1α activity in the isolated perfused beating rat atria under hypoxic conditions. Furthermore, both effects were modulated by the AC activator forskolin, through activation of CNP-PDE 3A signaling.展开更多
[Objectives] To determine the nine phenolic components in the leaves of Crataegus pinnatifida Bge. [Methods] The reversedphase high-performance liquid chromatography( RP-HPLC) was applied. [Results] Nine phenolic comp...[Objectives] To determine the nine phenolic components in the leaves of Crataegus pinnatifida Bge. [Methods] The reversedphase high-performance liquid chromatography( RP-HPLC) was applied. [Results] Nine phenolic components showed a good linear relationship in the range of 2-500 μg/m L with r in the range of 0. 999 5-0. 999 9. The recovery rate of spiked samples ranged from 93. 7% to110. 2%,and the relative standard deviation was in the range of 0. 69%-4. 58%. The leaves of 29 cultivars of C. pinnatifida Bge. were measured,and the average content of the nine phenolic components was as follows: isoquercitrin,hyperoside,procyanidin C1,procyanidin D1,epicatechin,procyanidin B2,chlorogenic acid,eucomic acid,and vitexin 2 "-O-rhamnoside. The contents of flavonoids and phenolic acids were high,up to 15 mg/g D. W,and the content of procyanidins was up to 6 mg/g D. W. [Conclusions]This method is easy and accurate in determination of phenolic components in the leaves of C. pinnatifida Bge.展开更多
Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury,but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression i...Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury,but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes(CMs) for driving the differentiation of cardiac stem cells(CSCs).Forced hypoxia-inducible factor 1α(HIF-1α) expression and physical hypoxia(5% O_2) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1α by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor(PD98059), but not inhibitors of JNK(SP600125), Notch(DAPT), NF-κB(PTDC), JAK(AG490), or STAT3(Stattic) suppressed hypoxiainduced Jagged1 protein expression in CMs. c-Kit^+ CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed GATA4, SM22α or vWF, but not Nkx2.5 and cTnI.Moreover, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU^+/Nkx2.5^+ cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced differentiation.Our results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling,and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures via HIF-1α/Jagged1/Notch signaling.展开更多
Despite high initial response rates,acute myeloid leukemia(AML)treated with the BCL-2-selective inhibitor venetoclax(VEN)alone or in combinations commonly acquires resistance.We performed gene/protein expression,metab...Despite high initial response rates,acute myeloid leukemia(AML)treated with the BCL-2-selective inhibitor venetoclax(VEN)alone or in combinations commonly acquires resistance.We performed gene/protein expression,metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN,and identified the activation of RAS/MAPK pathway,leading to increased stability and higher levels of MCL-1 protein,as a major acquired mechanism of VEN resistance.展开更多
基金partially supported by the National Natural Science Foundation of China (62372251)。
文摘Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and spectral information from PAN and LRMS images. Following the principle of gradual advance, this paper designs a novel network that contains two main logical functions, i.e., detail enhancement and progressive fusion, to solve the problem. More specifically, the detail enhancement module attempts to produce enhanced MS results with the same spatial sizes as corresponding PAN images, which are of higher quality than directly up-sampling LRMS images.Having a better MS base(enhanced MS) and its PAN, we progressively extract information from the PAN and enhanced MS images, expecting to capture pivotal and complementary information of the two modalities for the purpose of constructing the desired HRMS. Extensive experiments together with ablation studies on widely-used datasets are provided to verify the efficacy of our design, and demonstrate its superiority over other state-of-the-art methods both quantitatively and qualitatively. Our code has been released at https://github.com/JiaYN1/PAPS.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81802296)Natural Science Foundation of Tianjin(Grant No.18JCQNJC82500)Tianjin Municipality Science and Technology Commission Projects(Grant No.12ZCDZSY15600).
文摘Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)
文摘Objective:Bevacizumab is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor(VEGF)with clear clinical benefits.However,overall survival of some cancer types remains low owing to resistance to bevacizumab therapy.While resistance is commonly ascribed to tumor cell invasion induced by hypoxia-inducible factor(HIF),less attention has been paid to the potential involvement of endothelial cells(ECs)in vasculature activated by anti-angiogenic drugs.Methods:Human umbilical vein ECs(HUVECs),bEnd.3 cells,and mouse retinal microvascular ECs(MRMECs)were treated with bevacizumab under conditions of hypoxia and effects on biological behaviors,such as migration and tube formation,examined.Regulatory effects on TGFpi and CD 105(endoglin)were established via determination o f protein and mRNA levels.We further investigated whether the effects of bevacizumab could be reversed using the receptor tyrosine kinase inhibitor anlotinib.Results:Bevacizumab upregulated TGFpi as well as CD 105,a component o f the TGFP receptor complex and an angiogenesis promoter.Elevated CD 105 induced activation of Sm adl/5,the inflammatory pathway and endothelial-mesenchymal transition.The migration ability of HUVECs was enhanced by bevacizumab under hypoxia.Upregulation o f CD 105 was abrogated by anlotinib,which targets multiple receptor tyrosine kinases including VEGFR2/3,FGFR1-4,PD G FRα/β,C-Kit,and RET.Conclusions:Bevacizumab promotes migration and tube formation of HUVECs via activation of the TGFβi pathway and upregulation of CD105 expression.Anlotinib reverses the effects of bevacizumab by inhibiting the above signals.
文摘Our study investigated effects of C-type natriuretic peptide (CNP) on atrial dynamics and hypoxia inducible factor 1 alpha (HIF-1α) activity in perfused beating rat atria, under hypoxic conditions. Hypoxia significantly increased the levels of HIF-1α, concomitant with decreased trial dynamics. CNP (0.1 μmol/L) further decreased atrial dynamics under hypoxia and suppressed hypoxia-induced stimulation of HIF-1α expression. An adenylylcyclase (AC) activator, forskolin (0.1 μmol/L), significantly up-regulated atrial phosphodiesterase subtype 3A (PDE 3A) protein without affecting hypoxia-induced dynamics. In the presence of forskolin, the inhibitory effects of CNP on hypoxia-induced atrial dynamics and HIF-1α levels were significantly attenuated. Forskolin also prevented hypoxia-induced downregulation of PDE3A protein. These findings suggested that CNP inhibited atrial dynamics and HIF-1α activity in the isolated perfused beating rat atria under hypoxic conditions. Furthermore, both effects were modulated by the AC activator forskolin, through activation of CNP-PDE 3A signaling.
基金Supported by Project of Natural Science Foundation of Hebei Province(C2015204187)
文摘[Objectives] To determine the nine phenolic components in the leaves of Crataegus pinnatifida Bge. [Methods] The reversedphase high-performance liquid chromatography( RP-HPLC) was applied. [Results] Nine phenolic components showed a good linear relationship in the range of 2-500 μg/m L with r in the range of 0. 999 5-0. 999 9. The recovery rate of spiked samples ranged from 93. 7% to110. 2%,and the relative standard deviation was in the range of 0. 69%-4. 58%. The leaves of 29 cultivars of C. pinnatifida Bge. were measured,and the average content of the nine phenolic components was as follows: isoquercitrin,hyperoside,procyanidin C1,procyanidin D1,epicatechin,procyanidin B2,chlorogenic acid,eucomic acid,and vitexin 2 "-O-rhamnoside. The contents of flavonoids and phenolic acids were high,up to 15 mg/g D. W,and the content of procyanidins was up to 6 mg/g D. W. [Conclusions]This method is easy and accurate in determination of phenolic components in the leaves of C. pinnatifida Bge.
基金supported by grants from the National Natural Science Foundation of China (Grant Nos.81170121,81460042,81541004 and 81670254)Science and Technology Project of Guangdong Province (2016A020214016)+1 种基金YangFan Plan of Guangdong Province (4YF16007G)Excellent Graduate Student Training Program of Guangdong Medical University (YS2014013)
文摘Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury,but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes(CMs) for driving the differentiation of cardiac stem cells(CSCs).Forced hypoxia-inducible factor 1α(HIF-1α) expression and physical hypoxia(5% O_2) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1α by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor(PD98059), but not inhibitors of JNK(SP600125), Notch(DAPT), NF-κB(PTDC), JAK(AG490), or STAT3(Stattic) suppressed hypoxiainduced Jagged1 protein expression in CMs. c-Kit^+ CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed GATA4, SM22α or vWF, but not Nkx2.5 and cTnI.Moreover, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU^+/Nkx2.5^+ cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced differentiation.Our results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling,and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures via HIF-1α/Jagged1/Notch signaling.
基金This study is partially supported by NIH R01CA235622(to MK).
文摘Despite high initial response rates,acute myeloid leukemia(AML)treated with the BCL-2-selective inhibitor venetoclax(VEN)alone or in combinations commonly acquires resistance.We performed gene/protein expression,metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN,and identified the activation of RAS/MAPK pathway,leading to increased stability and higher levels of MCL-1 protein,as a major acquired mechanism of VEN resistance.