Anti-jamming solutions based on antenna arrays enhance the anti-jamming ability and the robustness of global navigation satellite system(GNSS)receiver remarkably.However,the performance of the receiver will deteriorat...Anti-jamming solutions based on antenna arrays enhance the anti-jamming ability and the robustness of global navigation satellite system(GNSS)receiver remarkably.However,the performance of the receiver will deteriorate significantly in the overloaded interferences scenario.We define the overloaded interferences scenario as where the number of interferences is more than or equal to the number of antenna arrays elements.In this paper,the effect mechanism of interferences with different incident directions is found by studying the anti-jamming performance of the adaptive space filter.The theoretical analysis and conclusions,which are first validated through numerical examples,reveal the relationships between the optimal weight vector and the eigenvectors of the input signal autocorrelation matrix,the relationships between the interference cancellation ratio(ICR),the signal to interference and noise power ratio(SINR)of the adaptive space filter output and the number of interferences,the eigenvalues of the input signal autocorrelation matrix.In addition,two simulation experiments are utilized to further corroborate the theoretical findings through soft anti-jamming receiver.The simulation results match well with the theoretical analysis results,thus validating the effect mechanism of overloaded interferences.The simulation results show that,for a four elements circular array,the performance difference is up to 19 dB with different incident directions of interferences.Anti-jamming performance evaluation and jamming deployment optimization can obtain more accurate and efficient results by using the conclusions.展开更多
To improve the diagnosis accuracy and self-adaptability of fatigue crack in ulterior place of the supporting shaft, time series and neural network are attempted to be applied in research on diag-nosing the fatigue cr...To improve the diagnosis accuracy and self-adaptability of fatigue crack in ulterior place of the supporting shaft, time series and neural network are attempted to be applied in research on diag-nosing the fatigue crack’s degree based on analyzing the vibration characteristics of the supporting shaft. By analyzing the characteristic parameter which is easy to be detected from the supporting shaft’s exterior, the time series model parameter which is hypersensitive to the situation of fatigue crack in ulterior place of the supporting shaft is the target input of neural network, and the fatigue crack’s degree value of supporting shaft is the output. The BP network model can be built and net-work can be trained after the structural parameters of network are selected. Furthermore, choosing the other two different group data can test the network. The test result will verify the validity of the BP network model. The result of experiment shows that the method of time series and neural network are effective to diagnose the occurrence and the development of the fatigue crack’s degree in ulterior place of the supporting shaft.展开更多
Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron...Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.展开更多
Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammo...Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.展开更多
The study is to assess the present serviceability rating of Nigerian highways and <span style="font-family:;" "=""><span style="font-family:Verdana;">the load damage effe...The study is to assess the present serviceability rating of Nigerian highways and <span style="font-family:;" "=""><span style="font-family:Verdana;">the load damage effects of overloaded trucks. The researchers used the American</span><span> </span><span style="font-family:Verdana;">Association of State Highway and Transportation Officials (AASHTO) methods. In this study, the highway section of Lokoja-Abuja, Ilorin-Jebba and Abakiliki-Ogoja via Mbok roads were selected, and data were collected through an axle-load survey, automatic traffic count and from secondary sources. The rate of gross vehicle weight violation was found, ranging from 20% to 94% of the axle load distribution across the studied network. Comparing the overloaded vehicle damage factor (V.D.F.) and standard V.D.F., the range was from 1.2 to 41.34 times across the road networks studied, and this explained why the pavement structures of Nigerian roads tend to deteri</span><span><span style="font-family:Verdana;">orate during its service life rapidly. Present serviceability rating was estimated at 3.45, 4.41 and 3.35 for Lokoja-Abuja, Ilorin-Jebba and Abakiliki-Ogoja roads respectively, showing depletion from their initial conditions. The damaging effects of the HGV are less severe at Lokoja-Abuja Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.30), followed by </span><span><span style="font-family:Verdana;">Ilorin-Jebba Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.35) and more in Abakiliki-Ogoja Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.43). The heaviest overload of 94% of the 6-axle vehicles plying at the Lokoja-Abuja road could explain this intense damaging effect on the road pavement</span></span></span></span>展开更多
Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obes...Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.展开更多
BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulatio...BACKGROUND Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients.Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs,especially when iron enters the cells via specific calcium channels.AIM To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.METHODS Five databases,including PubMed,Cochrane Library,Embase,ScienceDirect,and ClinicalTrials.gov,were systematically searched,and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria.The quality of the included studies was assessed based on the Cochrane collab-oration tool for bias assessment.The primary outcome assessed was myocardial-T2 and myocardial iron concentration,while the secondary results showed serum ferritin level,liver iron concentration,and treatment adverse outcomes.Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.RESULTS During the follow-up period,Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group[95%confidence interval(CI):0.34-5.24,P=0.03,I2=0%].Additionally,a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group[95%CI:-0.38-(-0.25),P<0.00001,I2=0%].Liver iron concentration was slightly lower in the amlodipine group by-0.04 mg/g,but this difference was not statistically significant(95%CI:-0.33-0.24,P=0.77,I2=0%).Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels(-328.86 ng/mL,95%CI:-1212.34-554.62,P=0.47,I2=90%).Regarding safety,there were no significant differences between the groups in the incidence of gastrointestinal upset,hypotension,or lower limb edema.CONCLUSION Amlodipine with iron chelation therapy significantly improved cardiac parameters,including cardiac-T2 and myocardial iron,in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.展开更多
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
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
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
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
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
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
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
To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanica...To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.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
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
Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bo...Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.展开更多
基金supported by the National Natural Science Foundation of China(62003354).
文摘Anti-jamming solutions based on antenna arrays enhance the anti-jamming ability and the robustness of global navigation satellite system(GNSS)receiver remarkably.However,the performance of the receiver will deteriorate significantly in the overloaded interferences scenario.We define the overloaded interferences scenario as where the number of interferences is more than or equal to the number of antenna arrays elements.In this paper,the effect mechanism of interferences with different incident directions is found by studying the anti-jamming performance of the adaptive space filter.The theoretical analysis and conclusions,which are first validated through numerical examples,reveal the relationships between the optimal weight vector and the eigenvectors of the input signal autocorrelation matrix,the relationships between the interference cancellation ratio(ICR),the signal to interference and noise power ratio(SINR)of the adaptive space filter output and the number of interferences,the eigenvalues of the input signal autocorrelation matrix.In addition,two simulation experiments are utilized to further corroborate the theoretical findings through soft anti-jamming receiver.The simulation results match well with the theoretical analysis results,thus validating the effect mechanism of overloaded interferences.The simulation results show that,for a four elements circular array,the performance difference is up to 19 dB with different incident directions of interferences.Anti-jamming performance evaluation and jamming deployment optimization can obtain more accurate and efficient results by using the conclusions.
基金This project is supported by National Natural Science Fundation of China (No. 50675066)Provincial Key Technologies R&D of Hunan, China (No. 05FJ2001)China Postdoctoral Science Foundation (No. 2005038006).
文摘To improve the diagnosis accuracy and self-adaptability of fatigue crack in ulterior place of the supporting shaft, time series and neural network are attempted to be applied in research on diag-nosing the fatigue crack’s degree based on analyzing the vibration characteristics of the supporting shaft. By analyzing the characteristic parameter which is easy to be detected from the supporting shaft’s exterior, the time series model parameter which is hypersensitive to the situation of fatigue crack in ulterior place of the supporting shaft is the target input of neural network, and the fatigue crack’s degree value of supporting shaft is the output. The BP network model can be built and net-work can be trained after the structural parameters of network are selected. Furthermore, choosing the other two different group data can test the network. The test result will verify the validity of the BP network model. The result of experiment shows that the method of time series and neural network are effective to diagnose the occurrence and the development of the fatigue crack’s degree in ulterior place of the supporting shaft.
基金Supported by Royal Golden Jubilee Ph D Program of Thailand Research Fund(Grant No.PHD/0345/2552)Faculty of Medicine Research Fund,Chiang Mai University,ThailandChair Professor Grant of National Science and Technology Development Agency through Professor Suthat Fucharoen,MD
文摘Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.
文摘Background:It is known to all that iron overload is a fatal adverse effect on cells and tissue.Herein,our study aimed to investigate the effects of curcumin on iron-overloaded stress in macrophages.Methods:Ferric ammonium citrate was added to the macrophage cell line(RAW264.7)to establish an iron-overloaded macrophage model.Cell counting kit 8 assay was used to detect cell viability.Superoxide dismutase,reactive oxygen species,malondialdehyde,and apoptosis were performed to analyze the severity of cellular oxidative damage.In addition,quantitative real-time polymerase chain reaction and western blot were used to detect the expression of nuclear factor erythroid 2-related factor 2.Results:The result showed that iron overload of macrophage was visualized by incubating in 40μM ferric ammonium citrate for 24 h.The curcumin significantly reversed the iron overload-induced apoptotic cells at low(10μM)and middle(20μM)concentrations.Additionally,the levels of malondialdehyde and reactive oxygen species activity in the groups of curcumin at low(10μM)and middle(20μM)concentrations were significantly decreased,while superoxide dismutase activity was obviously increased compared with that of the ferric ammonium citrate group alone.Finally,we found that low(10μM)and middle(20μM)dose curcumin up-regulated nuclear factor erythroid 2-related factor 2 expression at mRNA and protein levels compared with the ferric ammonium citrate group alone.Conclusion:Curcumin reduces iron-overloaded stress in macrophages by activating nuclear factor erythroid 2-related factor 2 and enhancing the superoxide dismutase activity,thereby protecting cell apoptosis.
文摘The study is to assess the present serviceability rating of Nigerian highways and <span style="font-family:;" "=""><span style="font-family:Verdana;">the load damage effects of overloaded trucks. The researchers used the American</span><span> </span><span style="font-family:Verdana;">Association of State Highway and Transportation Officials (AASHTO) methods. In this study, the highway section of Lokoja-Abuja, Ilorin-Jebba and Abakiliki-Ogoja via Mbok roads were selected, and data were collected through an axle-load survey, automatic traffic count and from secondary sources. The rate of gross vehicle weight violation was found, ranging from 20% to 94% of the axle load distribution across the studied network. Comparing the overloaded vehicle damage factor (V.D.F.) and standard V.D.F., the range was from 1.2 to 41.34 times across the road networks studied, and this explained why the pavement structures of Nigerian roads tend to deteri</span><span><span style="font-family:Verdana;">orate during its service life rapidly. Present serviceability rating was estimated at 3.45, 4.41 and 3.35 for Lokoja-Abuja, Ilorin-Jebba and Abakiliki-Ogoja roads respectively, showing depletion from their initial conditions. The damaging effects of the HGV are less severe at Lokoja-Abuja Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.30), followed by </span><span><span style="font-family:Verdana;">Ilorin-Jebba Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.35) and more in Abakiliki-Ogoja Road (with </span><i><span style="font-family:Verdana;">g</span></i><span style="font-family:Verdana;"> = 0.43). The heaviest overload of 94% of the 6-axle vehicles plying at the Lokoja-Abuja road could explain this intense damaging effect on the road pavement</span></span></span></span>
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.
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.
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.
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.
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supported in part by the National Nature Science Foundation(81874022 and 82172483 to Xinyu Liu,82102522 to Lianlei Wang,82072478 to Yunpeng Zhao,82072435 to Qiang Yang,82073437 to Weiwei Li,81930070 to Shiqing Feng,82272548 to Lei Cheng)Key R&D Project of Shandong Province(2022CXGC010503 to Xinyu Liu)+1 种基金Shandong Natural Science Foundation(ZR202102210113 to Lianlei Wang,ZR2020YQ54 to Yunpeng Zhao)Shandong Province Taishan Scholar Project(tsqn202211317 to Lianlei Wang).The authors thank the Translational Medicine Core Facility of Shandong University for the consultation and instrument availability that supported this work.
文摘To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.
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.
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 in part by National Natural Science Foundation of China(32271364 & 31971240)Interdisciplinary innovation project from West China Hospital of Stomatology, Sichuan University(RD-03-202305)。
文摘Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
