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
Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte ...Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology,but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated.展开更多
Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrha...Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measuremen...In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measurement system were performed.Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g.The onboard-measured time-resolved axial displacement,contact stress and overload values were successfully obtained and analysed.Uniaxial compression tests of the dummy HTPB propellant used in the gunlaunched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties.A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process.During the launch process,the dummy propellant grain exhibited large deformation due to the high acceleration overload,possibly leading to friction between the motor case and propellant grain.The calculated contact stress showed good agreement with the experimental results,though discrepancies in the overall displacement of the dummy propellant grain were observed.The dynamic mechanical response process of the dummy propellant grain was analysed in detail.The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.展开更多
Segmentally assembled bridges are increasinglyfinding engineering applications in recent years due to their unique advantages,especially as urban viaducts.Vehicle loads are one of the most important variable loads acti...Segmentally assembled bridges are increasinglyfinding engineering applications in recent years due to their unique advantages,especially as urban viaducts.Vehicle loads are one of the most important variable loads acting on bridge structures.Accordingly,the influence of overloaded vehicles on existing assembled bridge structures is an urgent concern at present.This paper establishes thefinite element model of the segmentally assembled bridge based on ABAQUS software and analyzes the influence of vehicle overload on an assembled girder bridge struc-ture.First,afinite element model corresponding to the target bridge is established based on ABAQUS software,and the load is controlled to simulate vehicle movement in each area of the traveling zone at different times.Sec-ond,the key cross-sections of segmental girder bridges are monitored in real time based on the force character-istics of continuous girder bridges,and they are compared with the simulation results.Finally,a material damage ontology model is introduced,and the structural damage caused by different overloading rates is compared and analyzed.Results show that thefinite element modeling method is accurate by comparing with on-site measured data,and it is suitable for the numerical simulation of segmental girder bridges;Dynamic sensors installed at 1/4L,1/2L,and 3/4L of the segmental girder main beams could be used to identify the dynamic response of segmental girder bridges;The bottom plate of the segmental girder bridge is mostly damaged at the position where the length of the precast beam section changes and the midspan position.With the increase in load,damage in the direction of the bridge develops faster than that in the direction of the transverse bridge.Thefindings of this study can guide maintenance departments in the management and maintenance of bridges and vehicles.展开更多
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to creat...Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.展开更多
Mitochondria play an important role in pressure overload-induced cardiac hypertrophy.The present study aimed to investigate the role of mitochondrial transient receptor potential vanilloid 3(TRPV3)in myocardial hypert...Mitochondria play an important role in pressure overload-induced cardiac hypertrophy.The present study aimed to investigate the role of mitochondrial transient receptor potential vanilloid 3(TRPV3)in myocardial hypertrophy.A 0.7 mm diameter U-shaped silver clip was used to clamp the abdominal aorta of Sprague Dawley(SD)rats and establish an animal model of abdominal aortic constriction(AAC).Rat H9C2 myocardial cells were treated with angiotensin II(Ang II)to establish a hypertrophic myocardial cell model,and TRPV3 expression was knocked down using TRPV3 small interfering RNA(siRNA).JC-1 probe was used to detect mitochondrial membrane potential(MMP).DHE probe was used to detect ROS generation.Enzyme activities of mitochondrial respiratory chain complex I and III and ATP production were detected by assay kits.Immunofluorescence staining was used to detect TRPV3 expression in H9C2 cells.Western blot was used to detect the protein expression levels ofβ-myosin heavy chain(β-MHC),mitochondrial TRPV3 and mitochondrial NOX4.The results showed that,in the rat AAC model heart tissue and H9C2 cells treated with Ang II,the protein expression levels ofβ-MHC,mitochondrial TRPV3 and mitochondrial NOX4 were up-regulated,MMP was decreased,ROS generation was increased,mitochondrial respiratory chain complex I and III enzyme activities were decreased,and ATP production was reduced.After knocking down mitochondrial TRPV3 in H9C2 cells,the protein expression levels ofβ-MHC and mitochondrial NOX4 were down-regulated,MMP was increased,ROS generation was decreased,mitochondrial respiratory chain complex I and III enzyme activities were increased,and ATP production was increased.These results suggest that mitochondrial TRPV3 in cardiomyocytes exacerbates mitochondrial dysfunction by up-regulating NOX4,thereby participating in the process of pressure overload-induced myocardial hypertrophy.展开更多
Cervical cancer stands is a formidablemalignancy that poses a significant threat towomen’s health.Calcium overload,a minimally invasive tumor treatment,aims to accumulate an excessive concentration of Ca^(2+)within m...Cervical cancer stands is a formidablemalignancy that poses a significant threat towomen’s health.Calcium overload,a minimally invasive tumor treatment,aims to accumulate an excessive concentration of Ca^(2+)within mitochondria,triggering apoptosis.Copper sulfide(CuS)represents a photothermal mediator for tumor hyperthermia.However,relying solely on thermotherapy often proves insufficient in controlling tumor growth.Curcumin(CUR),an herbal compound with anti-cancer properties,inhibits the efflux of exogenous Ca^(2+)while promoting its excretion from the endoplasmic reticulum into the cytoplasm.To harness these therapeutic modalities,we have developed a nanoplatform that incorporates hollow CuS nanoparticles(NPs)adorned with multiple CaCO_(3) particles and internally loaded with CUR.This nanocomposite exhibits high uptake and easy escape from lysosomes,along with the degradation of surrounding CaCO3,provoking the generation of abundant exogenous Ca^(2+)in situ,ultimately damaging the mitochondria of diseased cells.Impressively,under laser excitation,the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO_(3),synergistically enhancing the antitumor effect through photothermal therapy.Additionally,fluorescence imaging reveals the distribution of these nanovehicles in vivo,indicating their effective accumulation at the tumor site.This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer,achieved through cascade enhancement of calcium overload-based dual therapy.展开更多
Objective:To explore an intervention strategy for patients with fluid overload undergoing maintenance hemodialysis and to evaluate the effects of the LEARNS model on improving self-care agency and patient compliance.M...Objective:To explore an intervention strategy for patients with fluid overload undergoing maintenance hemodialysis and to evaluate the effects of the LEARNS model on improving self-care agency and patient compliance.Methods:A total of 76 patients with fluid overload undergoing maintenance hemodialysis at our hospital from March 2023 to March 2024 were selected for the study.Patients were randomly divided into two groups,with 38 in each group.The control group received conventional interventions,while the observation group was treated using the LEARNS model.Self-care agency,compliance,and quality of life outcomes in both groups were analyzed and compared.Results:Before the intervention,no statistically significant differences were observed in the self-care agency scores between the two groups(P>0.05).After the intervention,patients’self-care agency improved significantly,with the observation group showing notably higher scores than the control group(P<0.05).Patient compliance in the observation group was also significantly higher than in the control group(P<0.05).Quality of life,assessed using the SF-36 scale,showed no significant differences between the two groups prior to intervention(P>0.05).After the intervention,quality of life scores improved significantly in both groups,with the observation group exhibiting significantly higher scores than the control group(P<0.05).Conclusion:The LEARNS model is effective in improving patient compliance,enhancing self-care agency,and improving quality of life in maintenance hemodialysis patients with fluid overload,making it a promising approach for broader application.展开更多
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supported by grants from Natural Science Foundation of China grant No 82172491 (CN)National Natural Science Funds for Excellent Young Scholar No 82322044 (CN)+2 种基金National Key Research and Development Program of China (2022YFC3601902)Youth Talent Support Programme of Guangdong Provincial Association for Science and Technology (SKXRC202308)State-funded postdoctoral researcher program No GZC20231062 (CN)。
文摘Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology,but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated.
基金supported by the National Natural Science Foundation of China,Nos.U2004106 (to WY),81971061 (to JC)the Key Scientific Research Project of Colleges and Universities in Henan Province,No.21A320039 (to WY)。
文摘Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
文摘In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measurement system were performed.Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g.The onboard-measured time-resolved axial displacement,contact stress and overload values were successfully obtained and analysed.Uniaxial compression tests of the dummy HTPB propellant used in the gunlaunched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties.A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process.During the launch process,the dummy propellant grain exhibited large deformation due to the high acceleration overload,possibly leading to friction between the motor case and propellant grain.The calculated contact stress showed good agreement with the experimental results,though discrepancies in the overall displacement of the dummy propellant grain were observed.The dynamic mechanical response process of the dummy propellant grain was analysed in detail.The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.
基金supported in part by the Key Research Projects of Higher Education Institutions in Henan Province(Grant No.24A560021)in part by the Henan Postdoctoral Foundation(Grant No.202102015).
文摘Segmentally assembled bridges are increasinglyfinding engineering applications in recent years due to their unique advantages,especially as urban viaducts.Vehicle loads are one of the most important variable loads acting on bridge structures.Accordingly,the influence of overloaded vehicles on existing assembled bridge structures is an urgent concern at present.This paper establishes thefinite element model of the segmentally assembled bridge based on ABAQUS software and analyzes the influence of vehicle overload on an assembled girder bridge struc-ture.First,afinite element model corresponding to the target bridge is established based on ABAQUS software,and the load is controlled to simulate vehicle movement in each area of the traveling zone at different times.Sec-ond,the key cross-sections of segmental girder bridges are monitored in real time based on the force character-istics of continuous girder bridges,and they are compared with the simulation results.Finally,a material damage ontology model is introduced,and the structural damage caused by different overloading rates is compared and analyzed.Results show that thefinite element modeling method is accurate by comparing with on-site measured data,and it is suitable for the numerical simulation of segmental girder bridges;Dynamic sensors installed at 1/4L,1/2L,and 3/4L of the segmental girder main beams could be used to identify the dynamic response of segmental girder bridges;The bottom plate of the segmental girder bridge is mostly damaged at the position where the length of the precast beam section changes and the midspan position.With the increase in load,damage in the direction of the bridge develops faster than that in the direction of the transverse bridge.Thefindings of this study can guide maintenance departments in the management and maintenance of bridges and vehicles.
基金supported by the National Natural Science Foundation of China[No.U21A20334,82373544]Hebei Provincial Department of Science and Technology Centrally Guided Local Development Fund Project[236Z7705G]Occupational health risk assessment and the formulation of national occupational health standards[102393220020090000020].
文摘Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.
基金supported by the National Natural Science Foundation of China (No. 30872716)the Natural Science Foundation of Hubei Province,China (No. 2015CFB288)Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and immunotherapy (No. 2023KZL06)。
文摘Mitochondria play an important role in pressure overload-induced cardiac hypertrophy.The present study aimed to investigate the role of mitochondrial transient receptor potential vanilloid 3(TRPV3)in myocardial hypertrophy.A 0.7 mm diameter U-shaped silver clip was used to clamp the abdominal aorta of Sprague Dawley(SD)rats and establish an animal model of abdominal aortic constriction(AAC).Rat H9C2 myocardial cells were treated with angiotensin II(Ang II)to establish a hypertrophic myocardial cell model,and TRPV3 expression was knocked down using TRPV3 small interfering RNA(siRNA).JC-1 probe was used to detect mitochondrial membrane potential(MMP).DHE probe was used to detect ROS generation.Enzyme activities of mitochondrial respiratory chain complex I and III and ATP production were detected by assay kits.Immunofluorescence staining was used to detect TRPV3 expression in H9C2 cells.Western blot was used to detect the protein expression levels ofβ-myosin heavy chain(β-MHC),mitochondrial TRPV3 and mitochondrial NOX4.The results showed that,in the rat AAC model heart tissue and H9C2 cells treated with Ang II,the protein expression levels ofβ-MHC,mitochondrial TRPV3 and mitochondrial NOX4 were up-regulated,MMP was decreased,ROS generation was increased,mitochondrial respiratory chain complex I and III enzyme activities were decreased,and ATP production was reduced.After knocking down mitochondrial TRPV3 in H9C2 cells,the protein expression levels ofβ-MHC and mitochondrial NOX4 were down-regulated,MMP was increased,ROS generation was decreased,mitochondrial respiratory chain complex I and III enzyme activities were increased,and ATP production was increased.These results suggest that mitochondrial TRPV3 in cardiomyocytes exacerbates mitochondrial dysfunction by up-regulating NOX4,thereby participating in the process of pressure overload-induced myocardial hypertrophy.
基金This research was sponsored by the key research program of Ningbo(No.2023Z210)funded by Ningbo Natural Science Foundation(No.202003N4006)the Joint Research Funds of Department of Science&Technology of Shaanxi Province,Northwestern Polytechnical University(No.2020GXLH-Z-017).
文摘Cervical cancer stands is a formidablemalignancy that poses a significant threat towomen’s health.Calcium overload,a minimally invasive tumor treatment,aims to accumulate an excessive concentration of Ca^(2+)within mitochondria,triggering apoptosis.Copper sulfide(CuS)represents a photothermal mediator for tumor hyperthermia.However,relying solely on thermotherapy often proves insufficient in controlling tumor growth.Curcumin(CUR),an herbal compound with anti-cancer properties,inhibits the efflux of exogenous Ca^(2+)while promoting its excretion from the endoplasmic reticulum into the cytoplasm.To harness these therapeutic modalities,we have developed a nanoplatform that incorporates hollow CuS nanoparticles(NPs)adorned with multiple CaCO_(3) particles and internally loaded with CUR.This nanocomposite exhibits high uptake and easy escape from lysosomes,along with the degradation of surrounding CaCO3,provoking the generation of abundant exogenous Ca^(2+)in situ,ultimately damaging the mitochondria of diseased cells.Impressively,under laser excitation,the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO_(3),synergistically enhancing the antitumor effect through photothermal therapy.Additionally,fluorescence imaging reveals the distribution of these nanovehicles in vivo,indicating their effective accumulation at the tumor site.This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer,achieved through cascade enhancement of calcium overload-based dual therapy.
文摘Objective:To explore an intervention strategy for patients with fluid overload undergoing maintenance hemodialysis and to evaluate the effects of the LEARNS model on improving self-care agency and patient compliance.Methods:A total of 76 patients with fluid overload undergoing maintenance hemodialysis at our hospital from March 2023 to March 2024 were selected for the study.Patients were randomly divided into two groups,with 38 in each group.The control group received conventional interventions,while the observation group was treated using the LEARNS model.Self-care agency,compliance,and quality of life outcomes in both groups were analyzed and compared.Results:Before the intervention,no statistically significant differences were observed in the self-care agency scores between the two groups(P>0.05).After the intervention,patients’self-care agency improved significantly,with the observation group showing notably higher scores than the control group(P<0.05).Patient compliance in the observation group was also significantly higher than in the control group(P<0.05).Quality of life,assessed using the SF-36 scale,showed no significant differences between the two groups prior to intervention(P>0.05).After the intervention,quality of life scores improved significantly in both groups,with the observation group exhibiting significantly higher scores than the control group(P<0.05).Conclusion:The LEARNS model is effective in improving patient compliance,enhancing self-care agency,and improving quality of life in maintenance hemodialysis patients with fluid overload,making it a promising approach for broader application.
