Realistic urban scene generation has been extensively studied for the sake of the development of autonomous vehicles. However, the research has primarily focused on the synthesis of vehicles and pedestrians, while the...Realistic urban scene generation has been extensively studied for the sake of the development of autonomous vehicles. However, the research has primarily focused on the synthesis of vehicles and pedestrians, while the generation of cyclists is rarely presented due to its complexity. This paper proposes a perspective-aware and realistic cyclist generation method via object retrieval. Images, semantic maps, and depth labels of objects are first collected from existing datasets, categorized by class and perspective, and calculated by an algorithm newly designed according to imaging principles. During scene generation, objects with the desired class and perspective are retrieved from the collection and inserted into the background, which is then sent to the modified 2D synthesis model to generate images. This pipeline introduces a perspective computing method, utilizes object retrieval to control the perspective accurately, and modifies a diffusion model to achieve high fidelity. Experiments show that our proposal gets a 2.36 Fréchet Inception Distance, which is lower than the competitive methods, indicating a superior realistic expression ability. When these images are used for augmentation in the semantic segmentation task, the performance of ResNet-50 on the target class can be improved by 4.47%. These results demonstrate that the proposed method can be used to generate cyclists in corner cases to augment model training data, further enhancing the perception capability of autonomous vehicles and improving the safety performance of autonomous driving technology.展开更多
To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Ca...To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.展开更多
To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the pre...To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the preventive and therapeutic effects of GCBD on myocardial injury following chemotherapy.Then network pharmacology was employed to predict the targets of GCBD.Subsequently,a DOX-induced apoptosis model of H9C2 cardiomyocytes was established and co-cultured with serum containing GCBD serum.The viability and myocardial enzyme levels were evaluated using CCK8 assay and ELISA assay,TUNEL was using for apoptosis test.The GCBD effect was confirmed by tests of ROS andα-actinin levels,evaluation of mitochondrial morphology,and BAX co-localization with mitochondria.Furthermore,the expression levels of apoptosis-related molecules were determined via Western blotting.Additionally,a mouse model exhibiting DOX-induced cardiac functional impairment was generated and subsequently treated with GCBD.Myocardial enzyme level was tested at first,then echocardiography was tested,myocardial apoptosis in mice was observed through HE staining while related proteins were detected using IHC.Network pharmacological analyses revealed that GCBD exerts its effects on BAX,Caspase7,and other related molecules.Initially,we demonstrated the effective amelioration of DIC in cardiomyocyte viability,LDH/CK levels,α-actinin and ROS levels,and apoptosis by GCBD through improvements in TUNEL test,mitochondrial morphology and WB.The efficacy of GCBD in enhancing cardiac function in DIC mice has been validated through animal experiments.Taken together,our study showed that GCBD could significantly alleviate DOX induced myocardial injury by regulating mitochondrial apoptosis.The utilization of GCBD can effectively contribute to the prevention and treatment of chemotherapy-induced myocardial injury when anthracycline chemotherapy is employed in clinical practice.展开更多
Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 ...Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 gene was identified first via sequencing in patients with Gilbert syndrome complicated by aplastic anemia.Before the treatment for aplastic anemia,bilirubin and phenobarbitone tests were conducted.Patients were then treated for their primary disease and given ursodeoxycholic acid(UDCA)either with or without phenobarbitone.Results:The clinical practice of UDCA,which can alleviate increased bilirubin levels,did not affect the key treatments for aplastic anemia.Conclusions:These results indicate that Gilbert syndrome should be addressed when treating aplastic anemia.Furthermore,abnormal bilirubin levels can be controlled effectively by the UDCA treatment.展开更多
Aplastic anemia is a kind of disease mainly manifested by bone marrow failure.Autophagy is very important for cells to adjust the changes and maintain the balance of themselves.Patients with AA suffer from defects in ...Aplastic anemia is a kind of disease mainly manifested by bone marrow failure.Autophagy is very important for cells to adjust the changes and maintain the balance of themselves.Patients with AA suffer from defects in autophagy function,and the level of autophagy is closely related to the pathogenesis of AA.Autophagy may influence the proliferation and differentiation of HSC and their functional,hematopoietic microenvironmental and immune response,thereby mediating the occurrence and development of AA.This review will summarize the role of HSC,hematopoietic microenvironment and immune response in the pathogenesis of AA,and further elaborated the application of autophagy in regulating T cell subsets and the autophagy function of Treg cells in the treatment of AA.展开更多
In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated gr...In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells (BMNC)was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P<0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.展开更多
Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis...Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.展开更多
Objective:To investigate the changes in telomere length and the level of burst-forming units-erythrocyte(BFU-Es)and colony-forming unit-erythrocytes(CFU-Es)in mice with benzene-induced aplastic anemia(AA),and follow-u...Objective:To investigate the changes in telomere length and the level of burst-forming units-erythrocyte(BFU-Es)and colony-forming unit-erythrocytes(CFU-Es)in mice with benzene-induced aplastic anemia(AA),and follow-up the therapeutic effects of Angelica Polysaccharide(AP).Methods:Male BALB/c mice(n=120)were randomly divided into three groups(1,2,3):normal control(n=24),AA control(n=48),and treated AA(n=48),respectively.Mice in Group 2 received benzene inhalation for 2.5 months and 1 ml distilled water p.o.per day for 2 weeks after the establishment of AA models.Similar procedure was applied to the mice in Group 3 and AP was given for 2 weeks after the establishment of AA models.Real-time polymerase chain reaction was used to survey relative telomere length measurement of the bone marrow cells.A BFU-Es and CFU-Es survey was done to follow-up the therapeutic effects of AP.Results:Compared with normal control,significant reductions of RBC,WBC,and platelet counts were found in peripheral blood of AA mice.After treatment with AP,counts of BFU-Es and CFU-Es were restored up to 66.8%and 77.25%,respectively,and length of telomere was restored up to 76.34%,of the normal levels.The telomere length in treated AA group was higher than the control AA group.Conclusion:The AP can protect the telomere length and differentiation of hemopoietic stem/progenitor cells,accelerate the recovery of BFU-Es and CFU-Es of AA mice,and then improve the bone marrow failure.展开更多
Henoch-Schonlein purpura （HSP） is an IgA-mediated vasculitis which is easy to relapse. A lot of patients have to useglucocorticoids, immunosuppressive drugs and other drugs which will bring sorts of serious side eff...Henoch-Schonlein purpura （HSP） is an IgA-mediated vasculitis which is easy to relapse. A lot of patients have to useglucocorticoids, immunosuppressive drugs and other drugs which will bring sorts of serious side effects. Unfortunately,most of patients have to face the hurt of abdominal pain, arthritis, purpuric rash and renal involvement again after relapse.We have used Xiaochaihu decoration which is a famous formula in Shanghanlun to cure most of patients, especially whowith abdominal pain and purpuric rash. Due to the fact that this formula belongs to the Shaoyang Channels, interestingly,we find that these symptoms are located in regions close to the Shaoyang Channels. So that is the reason why Xiaochaihu decoration could work.展开更多
Multiple myeloma(MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10(NAT10) is the first reported regulator of mRNA acet...Multiple myeloma(MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10(NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing(ac RIP-seq) and ribosome profiling sequencing(Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170(CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover,CEP170 overexpression promoted cellular proliferation and chromosomal instability(CIN) in MM.Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP170 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.展开更多
Leaf senescence is the final stage of leaf development and appropriate onset and progression of leaf senescence are critical for reproductive success and fitness.Although great progress has been made in identifying ke...Leaf senescence is the final stage of leaf development and appropriate onset and progression of leaf senescence are critical for reproductive success and fitness.Although great progress has been made in identifying key genes regulating leaf senescence and elucidating the underlining mechanisms in the model plant Arabidopsis,there is still a gap to understanding the complex regulatory network.In this study,we discovered that Arabidopsis ANAC087 transcription factor(TF)positively modulated leaf senescence.Expression of ANAC087 was induced in senescing leaves and the encoded protein acted as a transcriptional activator.Both constitutive and inducible overexpression lines of ANAC087 showed earlier senescence than control plants,whereas T-DNA insertion mutation and dominant repression of the ANAC087 delayed senescence rate.A quantitative reverse transcription-polymerase chain reaction(qRT-PCR)profiling showed that the expression of an array of senescence-associated genes was upregulated in inducible ANAC087 overexpression plants including BFN1,NYE1,CEP1,RbohD,SAG13,SAG15,and VPEs,which are involved in programmed cell death(PCD),chlorophyll degradation and reactive oxygen species(ROS)accumulation.In addition,electrophoretic mobility shift assay(EMSA)and chromatin immunoprecipitation-quantitative polymerase chain reaction(ChIP-qPCR)assays demonstrated that ANAC087 directly bound to the canonical NAC recognition sequence(NACRS)motif in promoters of its target genes.Moreover,mutation of two representative target genes,BFN1 or NYE1 alleviated the senescence rate of ANAC087-overexpression plants,suggesting their genetic regulatory relationship.Taken together,this study indicates that ANAC087serves as an important regulator linking PCD,ROS,and chlorophyll degradation to leaf senescence.展开更多
基金supported by the Cultivation Program for Major Scientific Research Projects of Harbin Institute of Technology(ZDXMPY20180109).
文摘Realistic urban scene generation has been extensively studied for the sake of the development of autonomous vehicles. However, the research has primarily focused on the synthesis of vehicles and pedestrians, while the generation of cyclists is rarely presented due to its complexity. This paper proposes a perspective-aware and realistic cyclist generation method via object retrieval. Images, semantic maps, and depth labels of objects are first collected from existing datasets, categorized by class and perspective, and calculated by an algorithm newly designed according to imaging principles. During scene generation, objects with the desired class and perspective are retrieved from the collection and inserted into the background, which is then sent to the modified 2D synthesis model to generate images. This pipeline introduces a perspective computing method, utilizes object retrieval to control the perspective accurately, and modifies a diffusion model to achieve high fidelity. Experiments show that our proposal gets a 2.36 Fréchet Inception Distance, which is lower than the competitive methods, indicating a superior realistic expression ability. When these images are used for augmentation in the semantic segmentation task, the performance of ResNet-50 on the target class can be improved by 4.47%. These results demonstrate that the proposed method can be used to generate cyclists in corner cases to augment model training data, further enhancing the perception capability of autonomous vehicles and improving the safety performance of autonomous driving technology.
文摘To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.
基金supported by the National Natural Science Foundation of China(No.82074348,No.82274491)the innovation and development joint project of Shandong Province Natural Science Foundation(ZR2023LZL009)the Jinan clinical medical science and technology innovation plan(No.202225014,202328072).
文摘To observe the effects of GuiCaoBaiDu Decoction(GCBD)on chemotherapy especially doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC)and explore the mechanisms.The present study presents a case demonstrating the preventive and therapeutic effects of GCBD on myocardial injury following chemotherapy.Then network pharmacology was employed to predict the targets of GCBD.Subsequently,a DOX-induced apoptosis model of H9C2 cardiomyocytes was established and co-cultured with serum containing GCBD serum.The viability and myocardial enzyme levels were evaluated using CCK8 assay and ELISA assay,TUNEL was using for apoptosis test.The GCBD effect was confirmed by tests of ROS andα-actinin levels,evaluation of mitochondrial morphology,and BAX co-localization with mitochondria.Furthermore,the expression levels of apoptosis-related molecules were determined via Western blotting.Additionally,a mouse model exhibiting DOX-induced cardiac functional impairment was generated and subsequently treated with GCBD.Myocardial enzyme level was tested at first,then echocardiography was tested,myocardial apoptosis in mice was observed through HE staining while related proteins were detected using IHC.Network pharmacological analyses revealed that GCBD exerts its effects on BAX,Caspase7,and other related molecules.Initially,we demonstrated the effective amelioration of DIC in cardiomyocyte viability,LDH/CK levels,α-actinin and ROS levels,and apoptosis by GCBD through improvements in TUNEL test,mitochondrial morphology and WB.The efficacy of GCBD in enhancing cardiac function in DIC mice has been validated through animal experiments.Taken together,our study showed that GCBD could significantly alleviate DOX induced myocardial injury by regulating mitochondrial apoptosis.The utilization of GCBD can effectively contribute to the prevention and treatment of chemotherapy-induced myocardial injury when anthracycline chemotherapy is employed in clinical practice.
基金This study was supported by the National Natural Science Foundation of China(No.81202839)the National Natural Science Foundation of China(No.81774080)+1 种基金the“Taishan Scholar”Project Special Fund(tsqn201812145)the Study Abroad Funding by the People’s Government of Shandong Province and the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.
文摘Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 gene was identified first via sequencing in patients with Gilbert syndrome complicated by aplastic anemia.Before the treatment for aplastic anemia,bilirubin and phenobarbitone tests were conducted.Patients were then treated for their primary disease and given ursodeoxycholic acid(UDCA)either with or without phenobarbitone.Results:The clinical practice of UDCA,which can alleviate increased bilirubin levels,did not affect the key treatments for aplastic anemia.Conclusions:These results indicate that Gilbert syndrome should be addressed when treating aplastic anemia.Furthermore,abnormal bilirubin levels can be controlled effectively by the UDCA treatment.
基金National Natural Science Foundation of China(No.81774080)。
文摘Aplastic anemia is a kind of disease mainly manifested by bone marrow failure.Autophagy is very important for cells to adjust the changes and maintain the balance of themselves.Patients with AA suffer from defects in autophagy function,and the level of autophagy is closely related to the pathogenesis of AA.Autophagy may influence the proliferation and differentiation of HSC and their functional,hematopoietic microenvironmental and immune response,thereby mediating the occurrence and development of AA.This review will summarize the role of HSC,hematopoietic microenvironment and immune response in the pathogenesis of AA,and further elaborated the application of autophagy in regulating T cell subsets and the autophagy function of Treg cells in the treatment of AA.
基金the National Natural Science Foundation of China (No. 81202839)the National Natural Science Foundation of China (No. 81774080)+1 种基金the “Taishan Scholar” Project Special Fundthe Study Abroad Funding by the Shandong health science and technology association and the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.
文摘In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells (BMNC)was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P<0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.
基金This work was supported by the National Natural Science Foundation of China(No.82074348)the Taishan Scholar Project(tsqn201812145)the Key Technology Research and Development Program of Shandong(No.2019GSF108162).
文摘Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.
基金the National Natural Science Foundation of China(No.81202839/H2902)the China Postdoctoral Science Foundation funded project(No.2013T60680)+3 种基金the China Postdoctoral Science Foundation(No.2012M521356)the Natural Science Foundation of Shandong Province,China(No.ZR2012HQ023)the Jinan young star of science and technology plan(No.201406012)the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and Shandong University,China。
文摘Objective:To investigate the changes in telomere length and the level of burst-forming units-erythrocyte(BFU-Es)and colony-forming unit-erythrocytes(CFU-Es)in mice with benzene-induced aplastic anemia(AA),and follow-up the therapeutic effects of Angelica Polysaccharide(AP).Methods:Male BALB/c mice(n=120)were randomly divided into three groups(1,2,3):normal control(n=24),AA control(n=48),and treated AA(n=48),respectively.Mice in Group 2 received benzene inhalation for 2.5 months and 1 ml distilled water p.o.per day for 2 weeks after the establishment of AA models.Similar procedure was applied to the mice in Group 3 and AP was given for 2 weeks after the establishment of AA models.Real-time polymerase chain reaction was used to survey relative telomere length measurement of the bone marrow cells.A BFU-Es and CFU-Es survey was done to follow-up the therapeutic effects of AP.Results:Compared with normal control,significant reductions of RBC,WBC,and platelet counts were found in peripheral blood of AA mice.After treatment with AP,counts of BFU-Es and CFU-Es were restored up to 66.8%and 77.25%,respectively,and length of telomere was restored up to 76.34%,of the normal levels.The telomere length in treated AA group was higher than the control AA group.Conclusion:The AP can protect the telomere length and differentiation of hemopoietic stem/progenitor cells,accelerate the recovery of BFU-Es and CFU-Es of AA mice,and then improve the bone marrow failure.
基金This study was supported by the National Natural Science Foundation of China （No. 81202839）, the NationalNatural Science Foundation of China （No. 81774080）, the Natural Science Foundation of Shandong Province（ZR2012HQ023）,the Medical science and technology development Foundation of Shandong Province, China （No.2014WS0431）, the Jinan young star of science and technology plan （No. 201406012）, and the Affiliated Hospital ofShandong University of Traditional Chinese Medicine and Shandong University, China.
文摘Henoch-Schonlein purpura （HSP） is an IgA-mediated vasculitis which is easy to relapse. A lot of patients have to useglucocorticoids, immunosuppressive drugs and other drugs which will bring sorts of serious side effects. Unfortunately,most of patients have to face the hurt of abdominal pain, arthritis, purpuric rash and renal involvement again after relapse.We have used Xiaochaihu decoration which is a famous formula in Shanghanlun to cure most of patients, especially whowith abdominal pain and purpuric rash. Due to the fact that this formula belongs to the Shaoyang Channels, interestingly,we find that these symptoms are located in regions close to the Shaoyang Channels. So that is the reason why Xiaochaihu decoration could work.
基金supported by National Key R&D Program of China (2020YFA0509400) (to Ye Yang)National Natural Science Foundation of China 81970196 (to Chunyan Gu) and 82073885 (to Ye Yang)+4 种基金Natural Science Foundation of Jiangsu Province (China) BK20200097 (to Chunyan Gu)National Natural Science Foundation of China 82073888 (to Hongbo Wang)the Science and Technology Support Program for Youth Innovation in Universities of Shandong (China) (2019KJM009) (to Hongbo Wang)Bohai rim Advanced Research Institute for Drug Discovery (China) (LX211011) (to Hongbo Wang)Jiangsu Postgraduate Research and Practice Innovation Program (China) KYCX21_1769 (to Rongfang Wei)。
文摘Multiple myeloma(MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10(NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing(ac RIP-seq) and ribosome profiling sequencing(Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170(CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover,CEP170 overexpression promoted cellular proliferation and chromosomal instability(CIN) in MM.Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP170 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.
基金supported by the National Natural Science Foundation of China(32171953 to B.Y.and 32101782 to J.Y.)the Fundamental Research Funds for the Central Universities(2452017025 to Y.Q.J.)。
文摘Leaf senescence is the final stage of leaf development and appropriate onset and progression of leaf senescence are critical for reproductive success and fitness.Although great progress has been made in identifying key genes regulating leaf senescence and elucidating the underlining mechanisms in the model plant Arabidopsis,there is still a gap to understanding the complex regulatory network.In this study,we discovered that Arabidopsis ANAC087 transcription factor(TF)positively modulated leaf senescence.Expression of ANAC087 was induced in senescing leaves and the encoded protein acted as a transcriptional activator.Both constitutive and inducible overexpression lines of ANAC087 showed earlier senescence than control plants,whereas T-DNA insertion mutation and dominant repression of the ANAC087 delayed senescence rate.A quantitative reverse transcription-polymerase chain reaction(qRT-PCR)profiling showed that the expression of an array of senescence-associated genes was upregulated in inducible ANAC087 overexpression plants including BFN1,NYE1,CEP1,RbohD,SAG13,SAG15,and VPEs,which are involved in programmed cell death(PCD),chlorophyll degradation and reactive oxygen species(ROS)accumulation.In addition,electrophoretic mobility shift assay(EMSA)and chromatin immunoprecipitation-quantitative polymerase chain reaction(ChIP-qPCR)assays demonstrated that ANAC087 directly bound to the canonical NAC recognition sequence(NACRS)motif in promoters of its target genes.Moreover,mutation of two representative target genes,BFN1 or NYE1 alleviated the senescence rate of ANAC087-overexpression plants,suggesting their genetic regulatory relationship.Taken together,this study indicates that ANAC087serves as an important regulator linking PCD,ROS,and chlorophyll degradation to leaf senescence.
