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
Haemochromatosis is the most common genetic condition among people of European descent,resulting in iron overload and multi-organ dysfunction.Despite early detection and treatment advances,affected individuals experie...Haemochromatosis is the most common genetic condition among people of European descent,resulting in iron overload and multi-organ dysfunction.Despite early detection and treatment advances,affected individuals experience significant morbidity impacting their quality of life(QoL).To scope the literature for QoL issues and rank them in order of relevance by professional bodies.A literature search was conducted using PubMed,EMBASE,and MEDLINE in addition to a grey literature search against the eligibility criteria up to July 2023.Inclusion cri-teria included original articles with data concerning symptoms and QoL in patients with haemochromatosis.Nineteen issues were identified from 47 articles and scored by a haemochromatosis special interest group using a scale of 1 to 10(10=highest importance).Mean scores were then calculated for each issue.Fatigue,joint pain and sexual issues were key factors associated with impaired QoL.The least relevant were weight changes and abdominal pain.Other issues raised were anxiety,the development of diabetes,and concerns about genetics and family.This is the first scoping review examining common symptoms affecting QoL of patients with hereditary haemochromatosis.Further studies,including patient interviews and a randomised controlled trial,will inform a validated QoL questionnaire.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:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murin...Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by transapical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22 mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6%increase in LV diastolic diameter and a 55.1%decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5μL vs.41.8±3.4μL),reduced LV contractility(lower dP/dt max and Ees),and diminished LV compliance(smaller dP/dt min and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107%and a 122%increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.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
This study examined how exploitative leadership undermines employees’experience of flow with work role overload and traditionalist values.Data were collected from 361 staff members across diverse industries in China(...This study examined how exploitative leadership undermines employees’experience of flow with work role overload and traditionalist values.Data were collected from 361 staff members across diverse industries in China(females=58.17%,mean age=32.14,SD=5.83).Structural equation modeling results indicated that exploitative leadership reduces employees’work-related flow via increased role overload.Furthermore,employees’traditionality level moderates the exploitative leadership effects on role overload.Specifically,employees with higher traditionality reported lower role overload when experiencing exploitative leadership,suggesting that cultural values may buffer its negative impact.This study contributes to understanding the mechanism and contextual factors linking exploitative leadership to work-related flow,filling a gap in the literature.Organizations are encouraged to reduce exploitative leadership behaviors through leadership development programs and to consider employees’value orientations when designing work environments.展开更多
This paper introduces an innovative approach to the deployment of folding wings on cruise missiles,aiming to overcome the issues associated with explosive devices.The proposed solution involves employing NiTi shape me...This paper introduces an innovative approach to the deployment of folding wings on cruise missiles,aiming to overcome the issues associated with explosive devices.The proposed solution involves employing NiTi shape memory wires for a nonexplosive self-deploying wing mechanism.The fundamental concept of the design revolves around the utilization of NiTi wires,which contract upon electric heating.This contraction action severs the shear pin,consequently releasing the folded wings.The operational performance of the NiTi wire is thoroughly examined through a series of electro-thermo-mechanical tests,offering valuable insights for selecting the appropriate wire material.Moreover,the mechanical dynamics involved in the self-deploying process are elucidated through finite element simulations.The simulations highlight that the thermally-induced phase transformation within the NiTi wires generates substantial actuation forces,exceeding 700 N,and strokes of over 6 mm.These forces are deemed sufficient for breaking the aluminum shear pin and effecting wing deployment.The proposed mechanism’s practical viability is substantiated through prototype tests,which conclusively establish the superiority of the nonexplosive self-deploying wing mechanism when compared to conventional methods.The experimental outcomes underscore the mechanism’s capability to markedly reduce overload stress while remaining compliant with the designated requirements and constraints.展开更多
The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additio...The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.展开更多
Objective:To analyze the risk factors influencing volume overload in patients during the pre-dialysis and early post-dialysis period(peri-dialysis period)by investigating the current situation of volume management of ...Objective:To analyze the risk factors influencing volume overload in patients during the pre-dialysis and early post-dialysis period(peri-dialysis period)by investigating the current situation of volume management of such patients in our hospital,to reduce the incidence of volume overload during this period.Methods:A total of 86 patients in the peri-dialysis period(glomerular filtration rate eGFR less than 15 mL/(min·1.73 m')to three months after dialysis)who received outpatient treatment,inpatient treatment,and hemodialysis in the hospital from June 2022 to December 2023 were selected as the research objects.General information,clinical symptoms,and laboratory data of the patients were collected.According to the disease evolution process of the patients,they were divided into the non-dialysis stage and the initial dialysis stage.The volume load index of the patients,namely the overhydration(OH)value,was measured by the multi-frequency bioelectrical impedance method.The relevant factors affecting the volume load of patients in the peri-dialysis period were compared and analyzed.Results:In the non-dialysis stage,68 patients(86%)had volume overload,and 21 patients(21%)had normal volume load.In the initial dialysis stage,53 patients(61%)had volume overload,and 33 patients(38%)had normal volume load.Among the patients with volume overload in the two stages combined,the primary diseases were diabetic nephropathy at 29%,hypertensive nephropathy at 29%,primary nephropathy at 34%,and other renal damage at 8%.Complications included heart failure at 29%,respiratory tract infection at 32%,coronary heart disease at 9%,and anemia at 21%.Among the patients with volume overload,69%were male,52%were over 60 years old,53%had no family member accompaniment,57%had insomnia,and 55%had an educational level of junior high school or below.Conclusion:More than half of the patients in the peri-dialysis period in the hospital are in a state of volume overload,which should arouse the attention of the department.For male patients,those with hypertension,diabetes,insomnia,respiratory tract infection,anemia,and without family member accompaniment,corresponding intervention measures should be taken to reduce the incidence of volume overload during the peri-dialysis period.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
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
Concerning the capture problem against arbitrary maneuvering targets,whose overload is high maneuvering but upper bounded and velocity has advantages,this paper elucidates a three-dimensional multi-constraint analytic...Concerning the capture problem against arbitrary maneuvering targets,whose overload is high maneuvering but upper bounded and velocity has advantages,this paper elucidates a three-dimensional multi-constraint analytical capture zone,exhibiting prominent guiding significance to the initial states of the terminal guidance.Unlike most existing capture zone studies,which are represented by initial relative velocity,the proposed capture zone investigates the initial velocity heading angle and side-window angle.First,the asymptotic fast convergence anti-interference guidance law is presented via motion camouflage theory,and it meets the Field of View(FOV)constraint by theoretical analysis.On this basis,the capture zone is derived with overload limits based on the Lyapunov-based function.Then,it is converted to the form defined by the velocity heading and side-window angles,considering the FOV constraint.Finally,the sensitivity of the capture zone to the designed guidance algorithm’s different influencing factors and the gain boundary are deduced and analyzed to provide a theoretical basis for augmenting the analytical capture zone during a practical engagement.The findings reveal the capture zone correlation mechanism of terminal guidance law and give academic support to the subsequent acquisition of arbitrary maneuvering targets,which has potential application value.展开更多
Sparse code multiple access(SCMA)is a non-orthogonal multiple access(NOMA)scheme based on joint modulation and spread spectrum coding.It is ideal for future communication networks with a massive number of nodes due to...Sparse code multiple access(SCMA)is a non-orthogonal multiple access(NOMA)scheme based on joint modulation and spread spectrum coding.It is ideal for future communication networks with a massive number of nodes due to its ability to handle user overload.Introducing SCMA into visible light communication(VLC)systems can improve the data transmission capability of the system.However,designing a suitable codebook becomes a challenging problem when addressing the demands of massive connectivity scenarios.Therefore,this paper proposes a low-complexity design method for high-overload codebooks based on the minimum bit error rate(BER)criterion.Firstly,this paper constructs a new codebook with parameters based on the symmetric mother codebook structure by allocating the codeword power so that the power of each user codebook is unbalanced;then,the BER performance in the visible light communication system is optimized to obtain specific parameters;finally,the successive interference cancellation(SIC)detection algorithm is used at the receiver side.Simulation results show that the method proposed in this paper can converge quickly by utilizing a relatively small number of detection iterations.This can simultaneously reduce the complexity of design and detection,outperforming existing design methods for massive SCMA codebooks.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
Imperfections in the wheel-rail contact are one of the main sources of generation of railway vibrations. Consequently, it is essential to take expensive corrective maintenance measures, the results of which may be unk...Imperfections in the wheel-rail contact are one of the main sources of generation of railway vibrations. Consequently, it is essential to take expensive corrective maintenance measures, the results of which may be unknown. In order to assess the effectiveness of these measures, this paper develops a vehicle-track interaction model in the time domain of a curved track with presence of rail corrugation on the inner rail. To characterize the behavior of the track, a numerical finite element model is developed using ANSYS software, while the behavior of the vehicle is characterized by a unidirectional model of two masses developed with VAMPIRE PRO software. The overloads obtained with the dynamic model are applied to the numerical model and then, the vibrational response of the track is obtained. Results are validated with real data and used to assess the effectiveness of rail grinding in the reduction of wheel-rail forces and the vibration generation phenomenon.展开更多
A comparative study is performed between a crack closure model and the Willenborg model, which can calculate the fatigue crack growth rate under the overload effects. The modified virtual crack annealing(VCA) model is...A comparative study is performed between a crack closure model and the Willenborg model, which can calculate the fatigue crack growth rate under the overload effects. The modified virtual crack annealing(VCA) model is briefly reviewed, which is based on the equivalent plastic zone concept. In this method, the retardation phenomenon is explained by the crack closure level variation, which is derived from the interactions between forward and reverse plastic zones ahead of the crack tip. As a comparison, the Forman equation in conjunction with the Willenborg model is also reviewed. The retardation phenomenon is described by directly modifying the stress intensity factor. It is known that the large plastic zone created by the overload can decelerate the fatigue crack growth rate until the crack grows beyond this region. A relationship between the plastic zone and the modified stress intensity factor is developed, which is a mathematical fitting equation instead of physical-based formulation. The experimental data in aluminum alloys are used to validate these two models. Overall, good agreement is observed between the model predictions and the testing data. It is noted that the approach based on modified VCA model can give more accurate prediction curves than the Willenborg model.展开更多
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile ca...Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca<sup>2+</sup> overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca<sup>2+</sup> signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca<sup>2+</sup> elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca<sup>2+</sup> from stores in the intracellular endoplasmic reticulum and/or increased Ca<sup>2+</sup> entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca<sup>2+</sup> by the sarco/endoplasmic reticulum Ca<sup>2+</sup>-activated ATPase and plasma membrane Ca<sup>2+</sup>-ATPase pumps, which contribute to Ca<sup>2+</sup> overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca<sup>2+</sup> signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca<sup>2+</sup> signals in the pathogenesis of pancreatitis.展开更多
Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial in...Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.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.
文摘Haemochromatosis is the most common genetic condition among people of European descent,resulting in iron overload and multi-organ dysfunction.Despite early detection and treatment advances,affected individuals experience significant morbidity impacting their quality of life(QoL).To scope the literature for QoL issues and rank them in order of relevance by professional bodies.A literature search was conducted using PubMed,EMBASE,and MEDLINE in addition to a grey literature search against the eligibility criteria up to July 2023.Inclusion cri-teria included original articles with data concerning symptoms and QoL in patients with haemochromatosis.Nineteen issues were identified from 47 articles and scored by a haemochromatosis special interest group using a scale of 1 to 10(10=highest importance).Mean scores were then calculated for each issue.Fatigue,joint pain and sexual issues were key factors associated with impaired QoL.The least relevant were weight changes and abdominal pain.Other issues raised were anxiety,the development of diabetes,and concerns about genetics and family.This is the first scoping review examining common symptoms affecting QoL of patients with hereditary haemochromatosis.Further studies,including patient interviews and a randomised controlled trial,will inform a validated QoL questionnaire.
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.
基金Natural Science Foundation of Guangdong Province,Grant/Award Number:2023A1515110032 and 2022A1515220152Guangzhou Key Research and Development Program Foundation,Grant/Award Number:202206010199National Natural Science Foundation of China,Grant/Award Number:82100407,82272602 and 82370242。
文摘Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by transapical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22 mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6%increase in LV diastolic diameter and a 55.1%decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5μL vs.41.8±3.4μL),reduced LV contractility(lower dP/dt max and Ees),and diminished LV compliance(smaller dP/dt min and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107%and a 122%increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.
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.
文摘This study examined how exploitative leadership undermines employees’experience of flow with work role overload and traditionalist values.Data were collected from 361 staff members across diverse industries in China(females=58.17%,mean age=32.14,SD=5.83).Structural equation modeling results indicated that exploitative leadership reduces employees’work-related flow via increased role overload.Furthermore,employees’traditionality level moderates the exploitative leadership effects on role overload.Specifically,employees with higher traditionality reported lower role overload when experiencing exploitative leadership,suggesting that cultural values may buffer its negative impact.This study contributes to understanding the mechanism and contextual factors linking exploitative leadership to work-related flow,filling a gap in the literature.Organizations are encouraged to reduce exploitative leadership behaviors through leadership development programs and to consider employees’value orientations when designing work environments.
基金Supported by National Natural Science Foundation of China(Grant No.12372156).
文摘This paper introduces an innovative approach to the deployment of folding wings on cruise missiles,aiming to overcome the issues associated with explosive devices.The proposed solution involves employing NiTi shape memory wires for a nonexplosive self-deploying wing mechanism.The fundamental concept of the design revolves around the utilization of NiTi wires,which contract upon electric heating.This contraction action severs the shear pin,consequently releasing the folded wings.The operational performance of the NiTi wire is thoroughly examined through a series of electro-thermo-mechanical tests,offering valuable insights for selecting the appropriate wire material.Moreover,the mechanical dynamics involved in the self-deploying process are elucidated through finite element simulations.The simulations highlight that the thermally-induced phase transformation within the NiTi wires generates substantial actuation forces,exceeding 700 N,and strokes of over 6 mm.These forces are deemed sufficient for breaking the aluminum shear pin and effecting wing deployment.The proposed mechanism’s practical viability is substantiated through prototype tests,which conclusively establish the superiority of the nonexplosive self-deploying wing mechanism when compared to conventional methods.The experimental outcomes underscore the mechanism’s capability to markedly reduce overload stress while remaining compliant with the designated requirements and constraints.
文摘The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.
文摘Objective:To analyze the risk factors influencing volume overload in patients during the pre-dialysis and early post-dialysis period(peri-dialysis period)by investigating the current situation of volume management of such patients in our hospital,to reduce the incidence of volume overload during this period.Methods:A total of 86 patients in the peri-dialysis period(glomerular filtration rate eGFR less than 15 mL/(min·1.73 m')to three months after dialysis)who received outpatient treatment,inpatient treatment,and hemodialysis in the hospital from June 2022 to December 2023 were selected as the research objects.General information,clinical symptoms,and laboratory data of the patients were collected.According to the disease evolution process of the patients,they were divided into the non-dialysis stage and the initial dialysis stage.The volume load index of the patients,namely the overhydration(OH)value,was measured by the multi-frequency bioelectrical impedance method.The relevant factors affecting the volume load of patients in the peri-dialysis period were compared and analyzed.Results:In the non-dialysis stage,68 patients(86%)had volume overload,and 21 patients(21%)had normal volume load.In the initial dialysis stage,53 patients(61%)had volume overload,and 33 patients(38%)had normal volume load.Among the patients with volume overload in the two stages combined,the primary diseases were diabetic nephropathy at 29%,hypertensive nephropathy at 29%,primary nephropathy at 34%,and other renal damage at 8%.Complications included heart failure at 29%,respiratory tract infection at 32%,coronary heart disease at 9%,and anemia at 21%.Among the patients with volume overload,69%were male,52%were over 60 years old,53%had no family member accompaniment,57%had insomnia,and 55%had an educational level of junior high school or below.Conclusion:More than half of the patients in the peri-dialysis period in the hospital are in a state of volume overload,which should arouse the attention of the department.For male patients,those with hypertension,diabetes,insomnia,respiratory tract infection,anemia,and without family member accompaniment,corresponding intervention measures should be taken to reduce the incidence of volume overload during the peri-dialysis period.
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 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.
文摘Concerning the capture problem against arbitrary maneuvering targets,whose overload is high maneuvering but upper bounded and velocity has advantages,this paper elucidates a three-dimensional multi-constraint analytical capture zone,exhibiting prominent guiding significance to the initial states of the terminal guidance.Unlike most existing capture zone studies,which are represented by initial relative velocity,the proposed capture zone investigates the initial velocity heading angle and side-window angle.First,the asymptotic fast convergence anti-interference guidance law is presented via motion camouflage theory,and it meets the Field of View(FOV)constraint by theoretical analysis.On this basis,the capture zone is derived with overload limits based on the Lyapunov-based function.Then,it is converted to the form defined by the velocity heading and side-window angles,considering the FOV constraint.Finally,the sensitivity of the capture zone to the designed guidance algorithm’s different influencing factors and the gain boundary are deduced and analyzed to provide a theoretical basis for augmenting the analytical capture zone during a practical engagement.The findings reveal the capture zone correlation mechanism of terminal guidance law and give academic support to the subsequent acquisition of arbitrary maneuvering targets,which has potential application value.
基金supported in part by the National Science Foundation of China(NSFC)under Grant 62161024Jiangxi Provincial Natural Science Foundation under Grant 20224BAB212002+3 种基金Jiangxi Provincial Talent Project for Academic and Technical Leaders of Major Disciplines under Grant 20232BCJ23085,China Postdoctoral Science Foundation under Grant 2021TQ0136 and 2022M711463the State Key Laboratory of Computer Architecture(ICT,CAS)Open Project under Grant CARCHB202019supported in part by the National Natural Science Foundation of China(NSFC)under Grant 62061030supported in part by the National Natural Science Foundation of China(NSFC)under Grant 62161023。
文摘Sparse code multiple access(SCMA)is a non-orthogonal multiple access(NOMA)scheme based on joint modulation and spread spectrum coding.It is ideal for future communication networks with a massive number of nodes due to its ability to handle user overload.Introducing SCMA into visible light communication(VLC)systems can improve the data transmission capability of the system.However,designing a suitable codebook becomes a challenging problem when addressing the demands of massive connectivity scenarios.Therefore,this paper proposes a low-complexity design method for high-overload codebooks based on the minimum bit error rate(BER)criterion.Firstly,this paper constructs a new codebook with parameters based on the symmetric mother codebook structure by allocating the codeword power so that the power of each user codebook is unbalanced;then,the BER performance in the visible light communication system is optimized to obtain specific parameters;finally,the successive interference cancellation(SIC)detection algorithm is used at the receiver side.Simulation results show that the method proposed in this paper can converge quickly by utilizing a relatively small number of detection iterations.This can simultaneously reduce the complexity of design and detection,outperforming existing design methods for massive SCMA codebooks.
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.
文摘Imperfections in the wheel-rail contact are one of the main sources of generation of railway vibrations. Consequently, it is essential to take expensive corrective maintenance measures, the results of which may be unknown. In order to assess the effectiveness of these measures, this paper develops a vehicle-track interaction model in the time domain of a curved track with presence of rail corrugation on the inner rail. To characterize the behavior of the track, a numerical finite element model is developed using ANSYS software, while the behavior of the vehicle is characterized by a unidirectional model of two masses developed with VAMPIRE PRO software. The overloads obtained with the dynamic model are applied to the numerical model and then, the vibrational response of the track is obtained. Results are validated with real data and used to assess the effectiveness of rail grinding in the reduction of wheel-rail forces and the vibration generation phenomenon.
基金financially supported by the National Natural Science Foundation of China (No. 51405009)the Fundamental Research Funds for the Central Universities of China
文摘A comparative study is performed between a crack closure model and the Willenborg model, which can calculate the fatigue crack growth rate under the overload effects. The modified virtual crack annealing(VCA) model is briefly reviewed, which is based on the equivalent plastic zone concept. In this method, the retardation phenomenon is explained by the crack closure level variation, which is derived from the interactions between forward and reverse plastic zones ahead of the crack tip. As a comparison, the Forman equation in conjunction with the Willenborg model is also reviewed. The retardation phenomenon is described by directly modifying the stress intensity factor. It is known that the large plastic zone created by the overload can decelerate the fatigue crack growth rate until the crack grows beyond this region. A relationship between the plastic zone and the modified stress intensity factor is developed, which is a mathematical fitting equation instead of physical-based formulation. The experimental data in aluminum alloys are used to validate these two models. Overall, good agreement is observed between the model predictions and the testing data. It is noted that the approach based on modified VCA model can give more accurate prediction curves than the Willenborg model.
基金Supported by grants from the National Natural Science Foundation of China No.30171167,No.30901945the Specialized Research Fund for the Doctoral Program of Higher Education No.20130201130009
文摘Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca<sup>2+</sup> overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca<sup>2+</sup> signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca<sup>2+</sup> elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca<sup>2+</sup> from stores in the intracellular endoplasmic reticulum and/or increased Ca<sup>2+</sup> entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca<sup>2+</sup> by the sarco/endoplasmic reticulum Ca<sup>2+</sup>-activated ATPase and plasma membrane Ca<sup>2+</sup>-ATPase pumps, which contribute to Ca<sup>2+</sup> overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca<sup>2+</sup> signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca<sup>2+</sup> signals in the pathogenesis of pancreatitis.
文摘Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.
