The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplieative Gaussian coloured noise and additive Gaussian white noise is investigated. Firstly, ...The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplieative Gaussian coloured noise and additive Gaussian white noise is investigated. Firstly, the analytic expression of the quasi-steady distribution function Ps （x, t） is derived by applying the unified coloured noise approximation and the Novikov Theorem; Secondly, the expression of the signal-to-noise ratio （SNR） is obtained in the adiabatic limit to quantify the stochastic resonance. Finally, tile effects of the linear coefficient a, the nonlinear coefficient b, the linear time-delayed feedback coefficient c and the delay time r on Ps（x,t） and SNR^± are discussed. It is found that the effects of the linear coefficient and the nonlinear coefficient, the positive linear time-delayed feedback coefficient and the negative linear time-delayed feedback coefficient, the positive delayed time and the negative delayed time on Ps（x,t） and SNR^± are different, respectively. This discussion would be helpful to the study of the system reliability and controlling stochastic resonance.展开更多
The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractiona...The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractional-order dynamical systems.This feedback loop model incorporates several crucial mechanisms like the buffering process,IP_(3)-receptor,ryanodine receptor,plasma membrane Ca^(2+)ATPase and sarcoplasmic/endoplasmic reticulum calcium ATPase(SERCA)pump,leak,sodium-calcium exchanger,voltage-gated Ca^(2+)channel,Orai channels,DA-dependent IP_(3)synthesis,and others.By incorporating these mechanisms,the model aims to provide a more comprehensive and realistic understanding of the system under investigation.The present model incorporates fractional-order dynamics along both spatial and temporal dimensions to examine the impacts of superdiffusion and memory showing Brownian motion of Ca^(2+),IP_(3),and DA signaling molecules.The bidirectional feedback between calcium and IP_(3)signaling systems,unidirectional feedback between calcium and dopamine signaling systems,and unidirectional feedback between IP_(3)and dopamine signaling systems have been incorporated into the present model.These feedback loops establish interactions among calcium,IP_(3),and dopamine signaling systems within neuronal cells.The numerical findings were obtained by using the Crank-Nicholson method with the Grunwald technique for fractional space derivatives and the L1method for fractional time derivatives in conjunction with the Gauss-Seidel Iterations.This research specifically investigates the implications of cell memory as well as superdiffusion on Ca^(2+),IP_(3),and DA dynamics in neuronal cells,which are interactive nonlinear systems.The superdiffusion process results in a reduction in Ca^(2+),IP_(3),and DA concentrations,while cellular memory leads to an increase in ion and molecule concentrations in neuronal cells during the initial time.The disruption of any given process can lead to imbalances in calcium,IP_(3),and DA systems,hence contributing to neurotoxicity and cellular demise.展开更多
Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biologic...Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.展开更多
Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the...Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.展开更多
Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the ci...Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.展开更多
Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipa...Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients.Aloperine(ALO)is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation,allergies and infection.However,its therapeutic efficacy and underlying mechanism in CC are still unclear.In the current study,MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC.Then,the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry,respectively,while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay.Moreover,nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo.The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis.This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest.Simultaneously,ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio.Additionally,the migration and invasion of HeLa cells were attenuated by ALO treatment,which was considered to result from inhibition of epithelial-to-mesenchymal transition.For molecular mechanisms,the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment.This study indicated that ALO markedly suppresses the proliferation,migration and invasion and enhances the apoptosis of HeLa cells.In addition,these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.展开更多
Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this...Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this basis, this paper proposes dual loop feedback pre-distortion, which uses two first-order Volterra filter models to reduce the computing complexity and a dynamic error adjustment model to construct a revised feedback to ensure a better pre-distortion performance. The computation complexity, iterative convergence speed and precision of the proposed method are theoretically analyzed. Simulation results show that this dual loop feedback pre-distortion can speed the updating of coefficients and ensure the linearity of the amplifier output.展开更多
The existing kinematic parameter calibration method cannot further improve the absolute positioning accuracy of the robot due to the uncertainty of positioning error caused by robot joint backlash.In view of this prob...The existing kinematic parameter calibration method cannot further improve the absolute positioning accuracy of the robot due to the uncertainty of positioning error caused by robot joint backlash.In view of this problem,a closed‑loop feedback accuracy compensation method for robot joints was proposed.Firstly,a Chebyshev polynomial error estimation model was established which took geometric error and non‑geometric error into account.In addition,the absolute linear grating scale was installed at each joint of the robot and the positioning error of the robot end was mapped to the joint angle.And the joint angle corrected value was obtained.Furthermore,the closed‑loop feedback of robot joints was established to realize the online correction of the positioning error.Finally,an experiment on the KUKA KR210 industrial robot was conducted to demonstrate the effectiveness of the method.The result shows that the maximum absolute positioning error of the robot is reduced by 75%from 0.76 mm to 0.19 mm.This method can compensate the robot joint backlash effectively and further improve the absolute positioning accuracy of the robot.展开更多
Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and...Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and S-function simulation block of asynchronous motor owing feedback function was built in Matlab/Simulink software, the simulation block indicates that motor rotation speed and its output moment vary with load and time, and the motor is a dynamic feedback system in working process. The state space block was adopted to express model of the belt. Thus it created simulation model of established dynamic model of overall belt conveyor system with Mat- lab/Simulink software, and simulates the course of starting by properly setting simulation parameters, and processes data for visualization.展开更多
In this paper, a scheme of close-loop feedback is proposed to induce transition of spiral pattern in the excitable media, which is described with the modified FitzHugh-Nagumo model. The numerical simulation results co...In this paper, a scheme of close-loop feedback is proposed to induce transition of spiral pattern in the excitable media, which is described with the modified FitzHugh-Nagumo model. The numerical simulation results confirm that the stable rotating spiral wave is removed and the whole media becomes homogeneous when appropriate intensity of feedback is used no matter whether the coupling feedback is imposed on the whole media or the sites in one line in the media.展开更多
Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaini...Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaining an acceptable image size. We have followed here a different path to accelerate data acquisition by improving the feedback loop to achieve the same SPM image quality in a shorter time. While the feedback loop in a scanning probe microscope typically starts to probe a new pixel starting from the previous position, we have reduced the total control time by using an improved starting point for the feedback loop at each pixel. By exploiting the information of the already scanned pixels a forecast for the new pixel is created. We have successfully used several simple methods for a prognosis in MATLAB simulations like one dimensional linear or cubic extrapolation and others. Only scanning tunnelling microscope data from real experiments were used to test the forecasts. A doubling of the speed was achieved in the most favourable cases.展开更多
In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in ...In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in patients with septic shock.Quantitative RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy controls.The investigation involved the comparison between the two groups and tracking changes in the patient group over time.The finding revealed that upon admission,the patient group exhibited markedly elevated relative expression levels of HMGB1,which subsequently decreased over time.Conversely,the patient group displayed significantly reduced relative expression levels of miR-146b upon admission,which subsequently increased over time compared to the control group.Receiver operating characteristic(ROC)curves showed good predictive value for HMGB1 and miR-146b.The experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting mortality.Additionally,it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1.展开更多
Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction...Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction.Circular RNAs(circRNAs)are emerging as important regulators of cardiac fibrosis.Here,we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism.Functionally,circ-CELF1 was involved in enhancing fibrosis-related markers'expression and promoting the proliferation of cardiac fibroblasts(CFs),thereby exacerbating cardiac fibrosis.Mechanistically,circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3,leading to an elevation of BRPF3 protein levels.Additionally,BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene.Thus,the transcription of Celf1 was dramatically activated,thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis.Moreover,Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing,thereby establishing a feedback loop for circ-CELF1 production.Consequently,a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established,suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.展开更多
The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]]....The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]].Genetic and physicochemical processes control exine formation and genic male sterility(GMS)genes constitute a significant proportion of identified genetic factors[[1],[2],[3],[4]].To date,more than 200 GMS genes have been identified in plants[4,5].The precise molecular mechanisms underlying exine formation rely on genetic networks established by these GMS genes.However,the specific genetic networks underlying the exine formation remain unclear.展开更多
Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for ...Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for cooking and heating worldwide, exposure to biomass smoke(BS) is recognized as a significant risk factor for COPD. Recent clinical data have shown that BS-COPD patients have a Th2-type inflammatory profile significantly different from that in COPD induced by cigarette smoke. As COPD is essentially proinflammatory,however, the mechanism underlying this Th2-type anti-inflammatory profile remains elusive.In this work, a network model is applied to study BS-induced inflammatory dynamics. The network model involves several positive feedback loops, activations of which are responsible for different mechanisms by which clinical phenotypes of COPD are produced. Our modeling study in this work has identified a subset of BS-COPD patients with a mixed M1-and Th2-type inflammatory profile. The model’s prediction is in good agreement with clinical experiments and our in silico knockout simulations have demonstrated several important network components that play an important role in the disease. Our modeling study provides novel insight into BS-COPD progression, offering a rationale for targeted therapy and personalized medicine for treatment of the disease in future.展开更多
The wheel brake system safety is a complex problem which refers to its technical state, operating environment, human factors, etc., in aircraft landing taxiing process. Usually, professors consider system safety with ...The wheel brake system safety is a complex problem which refers to its technical state, operating environment, human factors, etc., in aircraft landing taxiing process. Usually, professors consider system safety with traditional probability techniques based on the linear chain of events. However, it could not comprehensively analyze system safety problems, especially in operating environment, interaction of subsystems, and human factors. Thus,we consider system safety as a control problem based on the system-theoretic accident model, the processes(STAMP) model and the system theoretic process analysis(STPA) technique to compensate the deficiency of traditional techniques. Meanwhile,system safety simulation is considered as system control simulation, and Monte Carlo methods are used which consider the range of uncertain parameters and operation deviation to quantitatively study system safety influence factors in control simulation. Firstly,we construct the STAMP model and STPA feedback control loop of the wheel brake system based on the system functional requirement. Then four unsafe control actions are identified, and causes of them are analyzed. Finally, we construct the Monte Carlo simulation model to analyze different scenarios under disturbance. The results provide a basis for choosing corresponding process model variables in constructing the context table and show that appropriate brake strategies could prevent hazards in aircraft landing taxiing.展开更多
Bacterial quorum sensing （QS） has attracted much interests and it is an important process of cell communication. Recently, Bassler et al. studied the phenomena of QS regulated by small RNAs and the experimental data...Bacterial quorum sensing （QS） has attracted much interests and it is an important process of cell communication. Recently, Bassler et al. studied the phenomena of QS regulated by small RNAs and the experimental data showed that smafl RNAs played important role in the QS of Vibrio harveyi and it can permit the fine-tuning of gene regulation and mmntenance of homeostasis. According to Michaelis-Menten kinetics and mass action law in this paper, we construct a mathematical model to investigate the mechanism induced QS by coexist of small RNA and signal molecular （AI） and show that there are periodic oscillation when the time delay and Hill coefficient exceed a critical value and the periodic oscillation produces the change of concentration and induces QS. These results are fit to the experimental results. In the meanwhile, we also get some theoretical value of Hopf Bifurcation on time deday. In addition, we also find this network is robust against noise.展开更多
Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate osc...Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate oscillation with proper parameters, and what the key ingredients for the oscillation are. In this paper the ranges of some function-related parameters which are favorable to sustained oscillations are considered. In particular, some oscillatory motifs appearing with high-frequency in most of the oscillatory GRNs are observed. Moreover, there are some anti-oscillatory motifs which have a strong oscillation repressing effect. Some conclusions analyzing these motif effects and constructing oscillatory GRNs are provided.展开更多
In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops （TTFLs） and a cAMP-mediated feedback loop. The model shows t...In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops （TTFLs） and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erba^-/^- -mutant mice, and help us make an experimentally-testable prediction： oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erba^-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.展开更多
Magnetrons are widely used in microwave-based industrial applications, which are rapidly developing. However, the coupling between their output frequency and power as well as their wideband spectra restricts their fur...Magnetrons are widely used in microwave-based industrial applications, which are rapidly developing. However, the coupling between their output frequency and power as well as their wideband spectra restricts their further application. In this work, the output frequency and power of a magnetron are decoupled by self-injection. Moreover, the spectral bandwidth is narrowed, and the phase noise is reduced for most loop phase values. In order to predict the frequency variation with loop phase and injection ratio, a theoretical model based on a circuit equivalent to the magnetron is developed. Furthermore, the developed model also shows that the self-injection magnetron is stabler than the free-running magnetron and that the magnetron＇s phase noise can be reduced significantly for most loop phase values. Experimental results confirm the conclusions obtained using the proposed model.展开更多
基金supported by National Natural Science Foundation of China under Grant Nos.10472091 and 10332030
文摘The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplieative Gaussian coloured noise and additive Gaussian white noise is investigated. Firstly, the analytic expression of the quasi-steady distribution function Ps （x, t） is derived by applying the unified coloured noise approximation and the Novikov Theorem; Secondly, the expression of the signal-to-noise ratio （SNR） is obtained in the adiabatic limit to quantify the stochastic resonance. Finally, tile effects of the linear coefficient a, the nonlinear coefficient b, the linear time-delayed feedback coefficient c and the delay time r on Ps（x,t） and SNR^± are discussed. It is found that the effects of the linear coefficient and the nonlinear coefficient, the positive linear time-delayed feedback coefficient and the negative linear time-delayed feedback coefficient, the positive delayed time and the negative delayed time on Ps（x,t） and SNR^± are different, respectively. This discussion would be helpful to the study of the system reliability and controlling stochastic resonance.
文摘The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractional-order dynamical systems.This feedback loop model incorporates several crucial mechanisms like the buffering process,IP_(3)-receptor,ryanodine receptor,plasma membrane Ca^(2+)ATPase and sarcoplasmic/endoplasmic reticulum calcium ATPase(SERCA)pump,leak,sodium-calcium exchanger,voltage-gated Ca^(2+)channel,Orai channels,DA-dependent IP_(3)synthesis,and others.By incorporating these mechanisms,the model aims to provide a more comprehensive and realistic understanding of the system under investigation.The present model incorporates fractional-order dynamics along both spatial and temporal dimensions to examine the impacts of superdiffusion and memory showing Brownian motion of Ca^(2+),IP_(3),and DA signaling molecules.The bidirectional feedback between calcium and IP_(3)signaling systems,unidirectional feedback between calcium and dopamine signaling systems,and unidirectional feedback between IP_(3)and dopamine signaling systems have been incorporated into the present model.These feedback loops establish interactions among calcium,IP_(3),and dopamine signaling systems within neuronal cells.The numerical findings were obtained by using the Crank-Nicholson method with the Grunwald technique for fractional space derivatives and the L1method for fractional time derivatives in conjunction with the Gauss-Seidel Iterations.This research specifically investigates the implications of cell memory as well as superdiffusion on Ca^(2+),IP_(3),and DA dynamics in neuronal cells,which are interactive nonlinear systems.The superdiffusion process results in a reduction in Ca^(2+),IP_(3),and DA concentrations,while cellular memory leads to an increase in ion and molecule concentrations in neuronal cells during the initial time.The disruption of any given process can lead to imbalances in calcium,IP_(3),and DA systems,hence contributing to neurotoxicity and cellular demise.
基金supported by the National Natural Science Foundation of China(Grant Nos.81902617 and 82100816)Guangdong Natural Science Foundation(Grant No.2021A1515012322)Guangzhou Basic and Applied Basic Research Subject-Young Doctor’s“Sailing”Project(Grant No.2024A04J4702).
文摘Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.
基金This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)+2 种基金National Natural Science Foundation(82261160657)Chang Jiang Scholars Program(J.-X.B.)Special Support Program of Guangdong(J.-X.B.)。
文摘Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073276 and 82273100)Science and Technology Project of Tianjin Binhai New Area Health Commission(Grant No.2022BWKY016)the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058).
文摘Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
基金This work was supported by the National Natural Science Foundation of China(No.82001850)Shanxi Basic Application Research(No.201901D211491)+2 种基金the Scientific Research Project of Shanxi Health Commission(No.2019038)the Doctoral Research Project of Shanxi Medical University(No.XD1901)the Doctoral Research Project of Shanxi Province(No.SD1901).
文摘Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients.Aloperine(ALO)is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation,allergies and infection.However,its therapeutic efficacy and underlying mechanism in CC are still unclear.In the current study,MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC.Then,the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry,respectively,while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay.Moreover,nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo.The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis.This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest.Simultaneously,ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio.Additionally,the migration and invasion of HeLa cells were attenuated by ALO treatment,which was considered to result from inhibition of epithelial-to-mesenchymal transition.For molecular mechanisms,the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment.This study indicated that ALO markedly suppresses the proliferation,migration and invasion and enhances the apoptosis of HeLa cells.In addition,these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
文摘Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this basis, this paper proposes dual loop feedback pre-distortion, which uses two first-order Volterra filter models to reduce the computing complexity and a dynamic error adjustment model to construct a revised feedback to ensure a better pre-distortion performance. The computation complexity, iterative convergence speed and precision of the proposed method are theoretically analyzed. Simulation results show that this dual loop feedback pre-distortion can speed the updating of coefficients and ensure the linearity of the amplifier output.
基金supported by the National Natural Science Foundation of China(Nos.51875287, 52075250)the Special Fund for Transformation of Scientific,and Technological Achievements of Jiangsu Province(No.BA2018053)
文摘The existing kinematic parameter calibration method cannot further improve the absolute positioning accuracy of the robot due to the uncertainty of positioning error caused by robot joint backlash.In view of this problem,a closed‑loop feedback accuracy compensation method for robot joints was proposed.Firstly,a Chebyshev polynomial error estimation model was established which took geometric error and non‑geometric error into account.In addition,the absolute linear grating scale was installed at each joint of the robot and the positioning error of the robot end was mapped to the joint angle.And the joint angle corrected value was obtained.Furthermore,the closed‑loop feedback of robot joints was established to realize the online correction of the positioning error.Finally,an experiment on the KUKA KR210 industrial robot was conducted to demonstrate the effectiveness of the method.The result shows that the maximum absolute positioning error of the robot is reduced by 75%from 0.76 mm to 0.19 mm.This method can compensate the robot joint backlash effectively and further improve the absolute positioning accuracy of the robot.
文摘Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and S-function simulation block of asynchronous motor owing feedback function was built in Matlab/Simulink software, the simulation block indicates that motor rotation speed and its output moment vary with load and time, and the motor is a dynamic feedback system in working process. The state space block was adopted to express model of the belt. Thus it created simulation model of established dynamic model of overall belt conveyor system with Mat- lab/Simulink software, and simulates the course of starting by properly setting simulation parameters, and processes data for visualization.
基金National Natural Science Foundation of China under Grant Nos.10747005 and 10602020Natural Science Foundation of the Education Department of Jiangsu Province of China under Grant No.08KJD110018
文摘In this paper, a scheme of close-loop feedback is proposed to induce transition of spiral pattern in the excitable media, which is described with the modified FitzHugh-Nagumo model. The numerical simulation results confirm that the stable rotating spiral wave is removed and the whole media becomes homogeneous when appropriate intensity of feedback is used no matter whether the coupling feedback is imposed on the whole media or the sites in one line in the media.
文摘Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaining an acceptable image size. We have followed here a different path to accelerate data acquisition by improving the feedback loop to achieve the same SPM image quality in a shorter time. While the feedback loop in a scanning probe microscope typically starts to probe a new pixel starting from the previous position, we have reduced the total control time by using an improved starting point for the feedback loop at each pixel. By exploiting the information of the already scanned pixels a forecast for the new pixel is created. We have successfully used several simple methods for a prognosis in MATLAB simulations like one dimensional linear or cubic extrapolation and others. Only scanning tunnelling microscope data from real experiments were used to test the forecasts. A doubling of the speed was achieved in the most favourable cases.
基金Supported by the Natural Science Foundation of Hubei Province(2021CFB026)Scientific Research Project of Hubei Pathophysiological Society(2021HBAP002)+2 种基金Medical Service Capacity Building and Health Personnel Training Project of the Central Government(New Finance Society[2022]No.255)Key Project of Science and Technology Program of Nanshan District,Shenzhen(NS2022014)Wu Jieping Medical Foundation Clinical Research Project(320.6750.2021-11-12)。
文摘In the face of the elevated incidence and mortality rate of septic shock in the ICU,this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1(HMGB1)and miR-146b in patients with septic shock.Quantitative RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy controls.The investigation involved the comparison between the two groups and tracking changes in the patient group over time.The finding revealed that upon admission,the patient group exhibited markedly elevated relative expression levels of HMGB1,which subsequently decreased over time.Conversely,the patient group displayed significantly reduced relative expression levels of miR-146b upon admission,which subsequently increased over time compared to the control group.Receiver operating characteristic(ROC)curves showed good predictive value for HMGB1 and miR-146b.The experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting mortality.Additionally,it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1.
基金supported by research grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Nos.2024ZD0521500 and 2024ZD0521501,China)the National Natural Science Foundation of China(82270246,82070240,82470280 and 82300493)+1 种基金the Natural Science Foundation of Heilongjiang Province of China(JJ2024LH2446)China Postdoctoral Science Foundation(2023MD734169,China).
文摘Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction.Circular RNAs(circRNAs)are emerging as important regulators of cardiac fibrosis.Here,we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism.Functionally,circ-CELF1 was involved in enhancing fibrosis-related markers'expression and promoting the proliferation of cardiac fibroblasts(CFs),thereby exacerbating cardiac fibrosis.Mechanistically,circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3,leading to an elevation of BRPF3 protein levels.Additionally,BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene.Thus,the transcription of Celf1 was dramatically activated,thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis.Moreover,Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing,thereby establishing a feedback loop for circ-CELF1 production.Consequently,a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established,suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
基金supported by the National Key Research and Development Program of China(2022YFF1003501 and 2023ZD04076)the National Natural Science Foundation of China(32330076 and 32301886)the Beijing Innovation Consortium of Agriculture Research System(BAIC02-2024).
文摘The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]].Genetic and physicochemical processes control exine formation and genic male sterility(GMS)genes constitute a significant proportion of identified genetic factors[[1],[2],[3],[4]].To date,more than 200 GMS genes have been identified in plants[4,5].The precise molecular mechanisms underlying exine formation rely on genetic networks established by these GMS genes.However,the specific genetic networks underlying the exine formation remain unclear.
基金This work was supported by the National Natural Science Foundation of China(No.21273209).
文摘Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for cooking and heating worldwide, exposure to biomass smoke(BS) is recognized as a significant risk factor for COPD. Recent clinical data have shown that BS-COPD patients have a Th2-type inflammatory profile significantly different from that in COPD induced by cigarette smoke. As COPD is essentially proinflammatory,however, the mechanism underlying this Th2-type anti-inflammatory profile remains elusive.In this work, a network model is applied to study BS-induced inflammatory dynamics. The network model involves several positive feedback loops, activations of which are responsible for different mechanisms by which clinical phenotypes of COPD are produced. Our modeling study in this work has identified a subset of BS-COPD patients with a mixed M1-and Th2-type inflammatory profile. The model’s prediction is in good agreement with clinical experiments and our in silico knockout simulations have demonstrated several important network components that play an important role in the disease. Our modeling study provides novel insight into BS-COPD progression, offering a rationale for targeted therapy and personalized medicine for treatment of the disease in future.
文摘The wheel brake system safety is a complex problem which refers to its technical state, operating environment, human factors, etc., in aircraft landing taxiing process. Usually, professors consider system safety with traditional probability techniques based on the linear chain of events. However, it could not comprehensively analyze system safety problems, especially in operating environment, interaction of subsystems, and human factors. Thus,we consider system safety as a control problem based on the system-theoretic accident model, the processes(STAMP) model and the system theoretic process analysis(STPA) technique to compensate the deficiency of traditional techniques. Meanwhile,system safety simulation is considered as system control simulation, and Monte Carlo methods are used which consider the range of uncertain parameters and operation deviation to quantitatively study system safety influence factors in control simulation. Firstly,we construct the STAMP model and STPA feedback control loop of the wheel brake system based on the system functional requirement. Then four unsafe control actions are identified, and causes of them are analyzed. Finally, we construct the Monte Carlo simulation model to analyze different scenarios under disturbance. The results provide a basis for choosing corresponding process model variables in constructing the context table and show that appropriate brake strategies could prevent hazards in aircraft landing taxiing.
基金Supported by National Natural Science Foundation of China under Grant Nos. 10802043 and 10832006, Program for Science ＆ Technology Innovation Talents in Universities of Henan under Grant No. 2009HASTIT033 and Key Disciplines of Shanghai municipality （$30104）
文摘Bacterial quorum sensing （QS） has attracted much interests and it is an important process of cell communication. Recently, Bassler et al. studied the phenomena of QS regulated by small RNAs and the experimental data showed that smafl RNAs played important role in the QS of Vibrio harveyi and it can permit the fine-tuning of gene regulation and mmntenance of homeostasis. According to Michaelis-Menten kinetics and mass action law in this paper, we construct a mathematical model to investigate the mechanism induced QS by coexist of small RNA and signal molecular （AI） and show that there are periodic oscillation when the time delay and Hill coefficient exceed a critical value and the periodic oscillation produces the change of concentration and induces QS. These results are fit to the experimental results. In the meanwhile, we also get some theoretical value of Hopf Bifurcation on time deday. In addition, we also find this network is robust against noise.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10975015)the National Basic Research Program of China (Grant No. 2007CB814800)
文摘Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate oscillation with proper parameters, and what the key ingredients for the oscillation are. In this paper the ranges of some function-related parameters which are favorable to sustained oscillations are considered. In particular, some oscillatory motifs appearing with high-frequency in most of the oscillatory GRNs are observed. Moreover, there are some anti-oscillatory motifs which have a strong oscillation repressing effect. Some conclusions analyzing these motif effects and constructing oscillatory GRNs are provided.
基金Project supported by the State Key Program of National Natural Science Foundation of China (Grant No 60736028)the National Natural Science Foundation of China (Grant Nos 10871074 and 60704045)the Research Fund for the Doctoral Program of Higher Education of China (Grant No 20070558053)
文摘In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops （TTFLs） and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erba^-/^- -mutant mice, and help us make an experimentally-testable prediction： oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erba^-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.
基金supported by the National Basic Research Program of China(Grant No.2013CB328902)the National Natural Science Foundation of China(Grant No.61501311)
文摘Magnetrons are widely used in microwave-based industrial applications, which are rapidly developing. However, the coupling between their output frequency and power as well as their wideband spectra restricts their further application. In this work, the output frequency and power of a magnetron are decoupled by self-injection. Moreover, the spectral bandwidth is narrowed, and the phase noise is reduced for most loop phase values. In order to predict the frequency variation with loop phase and injection ratio, a theoretical model based on a circuit equivalent to the magnetron is developed. Furthermore, the developed model also shows that the self-injection magnetron is stabler than the free-running magnetron and that the magnetron＇s phase noise can be reduced significantly for most loop phase values. Experimental results confirm the conclusions obtained using the proposed model.
