Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low...Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.展开更多
Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obes...Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.展开更多
BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulatio...BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs,especially when iron enters the cells via specific calcium channels.AIM To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.METHODS Five databases,including PubMed,Cochrane Library,Embase,ScienceDirect,and ClinicalTrials.gov,were systematically searched,and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria.The quality of the included studies was assessed based on the Cochrane collab-oration tool for bias assessment.The primary outcome assessed was myocardial-T2 and myocardial iron concentration,while the secondary results showed serum ferritin level,liver iron concentration,and treatment adverse outcomes.Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.RESULTS During the follow-up period,Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group[95%confidence interval(CI):0.34-5.24,P=0.03,I2=0%].Additionally,a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group[95%CI:-0.38-(-0.25),P<0.00001,I2=0%].Liver iron concentration was slightly lower in the amlodipine group by-0.04 mg/g,but this difference was not statistically significant(95%CI:-0.33-0.24,P=0.77,I2=0%).Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels(-328.86 ng/mL,95%CI:-1212.34-554.62,P=0.47,I2=90%).Regarding safety,there were no significant differences between the groups in the incidence of gastrointestinal upset,hypotension,or lower limb edema.CONCLUSION Amlodipine with iron chelation therapy significantly improved cardiac parameters,including cardiac-T2 and myocardial iron,in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.展开更多
When only a portion of the shield lining structures in a full-line tunnel are overloaded,their bearing and failure characteristics are significantly different from those in the full-line overloaded case.In existing st...When only a portion of the shield lining structures in a full-line tunnel are overloaded,their bearing and failure characteristics are significantly different from those in the full-line overloaded case.In existing studies,one or several segmental lining rings have been studied,with overload applied to selected lining rings to analyze the performance evolution of the lining structures;however,this approach fails to reveal the bearing and failure characteristics of shield lining rings under localized overload.To address this research gap,we employ 3D finite element modeling to investigate the mechanical performance and failure mechanisms of shield segmental linings under localized overload conditions,and compare the results with full-line overload scenarios.Additionally,the impact of reinforcing shield segmental linings with steel rings is studied to address issues arising from localized overloads.The results indicate that localized overloads lead to significant ring joint dislocation and higher stress on longitudinal bolts,potentially causing longitudinal bolt failure.Furthermore,the overall deformation of lining rings,segmental joint opening,and stress in circumferential bolts and steel bars is lower compared to full-line overloads.For the same overload level,the convergence deformation of the lining under full-line overload is 1.5 to 2.0 times higher than that under localized overload.For localized overload situations,a reinforcement scheme with steel rings spanning across two adjacent lining rings is more effective than installing steel rings within individual lining rings.This spanning ring reinforcement strategy not only enhances the structural rigidity of each ring,but also limits joint dislocation and reduces stress on longitudinal bolts,with the reduction in maximum ring joint dislocation ranging from 70%to 82%and the reduction in maximum longitudinal bolt stress ranging from 19%to 57%compared to reinforcement within rings.展开更多
In air combat,one effective way to counter an incoming missile attacking an aircraft is to launch a defense missile compared with traditional passive defense strategies such as decoy and electronic countermeasures.To ...In air combat,one effective way to counter an incoming missile attacking an aircraft is to launch a defense missile compared with traditional passive defense strategies such as decoy and electronic countermeasures.To address this issue,this paper proposes a three-body cooperative active defense guidance law with overload constraints from the perspective of a small speed ratio.First,a cooperative guidance-oriented model for active defense is established and linearized to provide a foundation for the design of the guidance law.Then,the essential quantity known as Zero-Effort-Miss(ZEM)is analyzed during the engagement process.In order to minimize the influence of inaccurate estimates of remaining flight time in the ZEM,the concept of Zero-Effort-Velocity(ZEV)is introduced.Subsequently,utilizing the sliding mode control method,the guidance law is designed by selecting the ZEM and ZEV as sliding mode surfaces,combined with the fast power reaching law,and its finite-time stability is analyzed using the Lyapunov method.Furthermore,to quantitatively evaluate the performance of the proposed active defense guidance law,the interception rendezvous angle index is introduced.The proposed active defense guidance law considers integrating information from the incoming missile,aircraft,and defense missile with fewer simplifications and assumptions,and ensures that the aircraft is effectively protected with less overload required for the defense missile.Finally,simulation experiments demonstrate the effectiveness and adaptability of the proposed active defense guidance law.展开更多
Along with the progress of sciences and technologies, a lot of explorations are taken in many countries or organizations in succession. Lunar, the natural satellite of the earth, become a focus of the space discovery ...Along with the progress of sciences and technologies, a lot of explorations are taken in many countries or organizations in succession. Lunar, the natural satellite of the earth, become a focus of the space discovery again recently because of its abundant resource and high value in use. Lunar exploration is also one of the most important projects in China. A primary objective of the probe in lunar is to soft-land a manned spacecraft on the lunar surface. The soft-landing system is the key composition of the lunar lander. In the overall design of lunar lander, the analysis of touchdown dynamics during landing stage is an important work. The rigid-flexible coupling dynamics of a system with flexible cantilevers attached to the main lander is analyzed. The equations are derived from the subsystem method. Results show that the deformations of cantilevers have considerable effect on the overloading of the lunar lander system.展开更多
BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an import...BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.展开更多
The discovery of the natriuretic peptide system in the early 1980s aroused great interest among clinical cardiologists. The heart was not a mechanical pump alone, but also an endocrine organ that had powerful effects ...The discovery of the natriuretic peptide system in the early 1980s aroused great interest among clinical cardiologists. The heart was not a mechanical pump alone, but also an endocrine organ that had powerful effects on blood circulation. Natriuretic peptides caused both natriuresis and diuresis, and they responded to a volume overload which caused either stretch or pressure on the heart. As a result, the findings led to the conclusion that the human body had a hormone with effects similar to those of a drug which treats high blood pressure. Later, it became evident that the volume contraction was fortified by extrarenal plasma shift. Here, a hypothesis is presented in which the role of natriuretic peptides is to regulate oxygen transport as the volume contraction leads to hemoconcentration with an increased oxygen-carrying capacity. Wall stress, either chemical or mechanical, changes the oxygen gradient of the myocardium and affects the diffusion of oxygen within a myocyte. In support of this hypothesis, hypoxia-response elements have been found in both the atrial natriuretic peptide and the brain natriuretic peptide genes.展开更多
Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in ...Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.展开更多
The analysis of slope earthquake stability is one of the most important research subjects in geotechnical engineering and earthquake engineering.Two different concepts of slope earthquake stability are put forward：st...The analysis of slope earthquake stability is one of the most important research subjects in geotechnical engineering and earthquake engineering.Two different concepts of slope earthquake stability are put forward：strength reserve stability and dynamic overloading stability.The first concept of slope earthquake stability has been widely accepted,and relative analysis methods are also well de-veloped;the second one,however,is seldom mentioned until now,and the failure criterion and the analysis method based on this concept are yet to be explored.What are researched are just the failure criterion and the analysis method of dynamic overloading earthquake stability.The criterion of critical earthquake peak acceleration for the dynamic overloading stability of a slope and its analysis method,the load increasing method（LIM）,are put forward.The dynamic overloading earthquake stability of a loess slope at Changshougou（长寿沟） in Baoji（宝鸡） City,Shaanxi（陕西） Province,China,is analyzed with LIM.The analysis result reveals that the dynamic overloading earthquake stability of the slope is quite high to the action of the earthquake ground motion,with exceeding probability of 10% in the next 50 years.展开更多
The effect of single overload on the fatigue crack growth in 2024-T3 and 7075-T6 Al alloys was analyzed.Fatigue tests under constantamplitude loading with overload peak were carried out on V-notched specimens.Fractogr...The effect of single overload on the fatigue crack growth in 2024-T3 and 7075-T6 Al alloys was analyzed.Fatigue tests under constantamplitude loading with overload peak were carried out on V-notched specimens.Fractographic analysis was used as a principal approach to explain the crack growth retardation due to the overload.Scanning electron microscopy(SEM)analyses were conducted on the fractured surface of failed specimens to study the retardation effect.The obtained results show that the overload application generates a plastic zone in both aluminum alloys.The generated plastic zone is three times larger in the case of 2024-T3 compared to 7075-T6,and thus,a significant crack retardation was induced for 2024-T3.The retardation effect due to the overload for 2024-T3 and 7075-T6 lasted for about 10 mm and 1 mm,respectively,from the point of overload application.展开更多
BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver ...BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non- alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serummarkers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.展开更多
基金supported by China International Medical Foundation(Z-2019-42-1908-4)Natural Science Basic Research Program of Shaanxi Province(2019JM-440).
文摘Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.
基金supported by the National Natural Science Foundation of China(No.22101086)Guangzhou Basic and Applied Basic Research Project(No.202201010052)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515140030).
文摘Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.
文摘BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs,especially when iron enters the cells via specific calcium channels.AIM To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.METHODS Five databases,including PubMed,Cochrane Library,Embase,ScienceDirect,and ClinicalTrials.gov,were systematically searched,and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria.The quality of the included studies was assessed based on the Cochrane collab-oration tool for bias assessment.The primary outcome assessed was myocardial-T2 and myocardial iron concentration,while the secondary results showed serum ferritin level,liver iron concentration,and treatment adverse outcomes.Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.RESULTS During the follow-up period,Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group[95%confidence interval(CI):0.34-5.24,P=0.03,I2=0%].Additionally,a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group[95%CI:-0.38-(-0.25),P<0.00001,I2=0%].Liver iron concentration was slightly lower in the amlodipine group by-0.04 mg/g,but this difference was not statistically significant(95%CI:-0.33-0.24,P=0.77,I2=0%).Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels(-328.86 ng/mL,95%CI:-1212.34-554.62,P=0.47,I2=90%).Regarding safety,there were no significant differences between the groups in the incidence of gastrointestinal upset,hypotension,or lower limb edema.CONCLUSION Amlodipine with iron chelation therapy significantly improved cardiac parameters,including cardiac-T2 and myocardial iron,in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.
基金supported by the National Natural Science Foundation of China(No.52008308).
文摘When only a portion of the shield lining structures in a full-line tunnel are overloaded,their bearing and failure characteristics are significantly different from those in the full-line overloaded case.In existing studies,one or several segmental lining rings have been studied,with overload applied to selected lining rings to analyze the performance evolution of the lining structures;however,this approach fails to reveal the bearing and failure characteristics of shield lining rings under localized overload.To address this research gap,we employ 3D finite element modeling to investigate the mechanical performance and failure mechanisms of shield segmental linings under localized overload conditions,and compare the results with full-line overload scenarios.Additionally,the impact of reinforcing shield segmental linings with steel rings is studied to address issues arising from localized overloads.The results indicate that localized overloads lead to significant ring joint dislocation and higher stress on longitudinal bolts,potentially causing longitudinal bolt failure.Furthermore,the overall deformation of lining rings,segmental joint opening,and stress in circumferential bolts and steel bars is lower compared to full-line overloads.For the same overload level,the convergence deformation of the lining under full-line overload is 1.5 to 2.0 times higher than that under localized overload.For localized overload situations,a reinforcement scheme with steel rings spanning across two adjacent lining rings is more effective than installing steel rings within individual lining rings.This spanning ring reinforcement strategy not only enhances the structural rigidity of each ring,but also limits joint dislocation and reduces stress on longitudinal bolts,with the reduction in maximum ring joint dislocation ranging from 70%to 82%and the reduction in maximum longitudinal bolt stress ranging from 19%to 57%compared to reinforcement within rings.
基金support provided by the National Natural Science Foundation of China(No.62173274)the National Key R&D Program of China(No.2019YFA0405300)+3 种基金the Natural Science Foundation of Hunan Province of China(No.2021JJ10045)Shanghai Aerospace Science and Technology Innovation Fund,China(No.SAST2020-004)Postdoctoral Fellowship Program of CPSF(No.GZB20240989)the Open Research Subject of State Key Laboratory of Intelligent Game,China(No.ZBKF-24-01).
文摘In air combat,one effective way to counter an incoming missile attacking an aircraft is to launch a defense missile compared with traditional passive defense strategies such as decoy and electronic countermeasures.To address this issue,this paper proposes a three-body cooperative active defense guidance law with overload constraints from the perspective of a small speed ratio.First,a cooperative guidance-oriented model for active defense is established and linearized to provide a foundation for the design of the guidance law.Then,the essential quantity known as Zero-Effort-Miss(ZEM)is analyzed during the engagement process.In order to minimize the influence of inaccurate estimates of remaining flight time in the ZEM,the concept of Zero-Effort-Velocity(ZEV)is introduced.Subsequently,utilizing the sliding mode control method,the guidance law is designed by selecting the ZEM and ZEV as sliding mode surfaces,combined with the fast power reaching law,and its finite-time stability is analyzed using the Lyapunov method.Furthermore,to quantitatively evaluate the performance of the proposed active defense guidance law,the interception rendezvous angle index is introduced.The proposed active defense guidance law considers integrating information from the incoming missile,aircraft,and defense missile with fewer simplifications and assumptions,and ensures that the aircraft is effectively protected with less overload required for the defense missile.Finally,simulation experiments demonstrate the effectiveness and adaptability of the proposed active defense guidance law.
基金HI-tech Research and Development Program of China
文摘Along with the progress of sciences and technologies, a lot of explorations are taken in many countries or organizations in succession. Lunar, the natural satellite of the earth, become a focus of the space discovery again recently because of its abundant resource and high value in use. Lunar exploration is also one of the most important projects in China. A primary objective of the probe in lunar is to soft-land a manned spacecraft on the lunar surface. The soft-landing system is the key composition of the lunar lander. In the overall design of lunar lander, the analysis of touchdown dynamics during landing stage is an important work. The rigid-flexible coupling dynamics of a system with flexible cantilevers attached to the main lander is analyzed. The equations are derived from the subsystem method. Results show that the deformations of cantilevers have considerable effect on the overloading of the lunar lander system.
基金supported by a grant from Polish National Science Centre(2011/01/B/NZ6/00320)
文摘BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.
文摘The discovery of the natriuretic peptide system in the early 1980s aroused great interest among clinical cardiologists. The heart was not a mechanical pump alone, but also an endocrine organ that had powerful effects on blood circulation. Natriuretic peptides caused both natriuresis and diuresis, and they responded to a volume overload which caused either stretch or pressure on the heart. As a result, the findings led to the conclusion that the human body had a hormone with effects similar to those of a drug which treats high blood pressure. Later, it became evident that the volume contraction was fortified by extrarenal plasma shift. Here, a hypothesis is presented in which the role of natriuretic peptides is to regulate oxygen transport as the volume contraction leads to hemoconcentration with an increased oxygen-carrying capacity. Wall stress, either chemical or mechanical, changes the oxygen gradient of the myocardium and affects the diffusion of oxygen within a myocyte. In support of this hypothesis, hypoxia-response elements have been found in both the atrial natriuretic peptide and the brain natriuretic peptide genes.
基金supported by the National Natural Science Foundation of China,No.81273983
文摘Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.
基金supported by the National Natural Science Foundation of China (No. 40902086)
文摘The analysis of slope earthquake stability is one of the most important research subjects in geotechnical engineering and earthquake engineering.Two different concepts of slope earthquake stability are put forward：strength reserve stability and dynamic overloading stability.The first concept of slope earthquake stability has been widely accepted,and relative analysis methods are also well de-veloped;the second one,however,is seldom mentioned until now,and the failure criterion and the analysis method based on this concept are yet to be explored.What are researched are just the failure criterion and the analysis method of dynamic overloading earthquake stability.The criterion of critical earthquake peak acceleration for the dynamic overloading stability of a slope and its analysis method,the load increasing method（LIM）,are put forward.The dynamic overloading earthquake stability of a loess slope at Changshougou（长寿沟） in Baoji（宝鸡） City,Shaanxi（陕西） Province,China,is analyzed with LIM.The analysis result reveals that the dynamic overloading earthquake stability of the slope is quite high to the action of the earthquake ground motion,with exceeding probability of 10% in the next 50 years.
基金the Deanship of Scientific Research at King Saud University for funding the work through the research group (No. RGP-VPP-035)
文摘The effect of single overload on the fatigue crack growth in 2024-T3 and 7075-T6 Al alloys was analyzed.Fatigue tests under constantamplitude loading with overload peak were carried out on V-notched specimens.Fractographic analysis was used as a principal approach to explain the crack growth retardation due to the overload.Scanning electron microscopy(SEM)analyses were conducted on the fractured surface of failed specimens to study the retardation effect.The obtained results show that the overload application generates a plastic zone in both aluminum alloys.The generated plastic zone is three times larger in the case of 2024-T3 compared to 7075-T6,and thus,a significant crack retardation was induced for 2024-T3.The retardation effect due to the overload for 2024-T3 and 7075-T6 lasted for about 10 mm and 1 mm,respectively,from the point of overload application.
基金supported by agrant from Medical University of Gdansk(W-175)
文摘BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non- alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serummarkers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.
