Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and hea...Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.展开更多
[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore ...[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore the nonlinear response relationship between phytoplankton community structure and its driving factors in spring and autumn in Furong Creek under the construction of cascade weirs.[Methods]The structure of phytoplankton communities and related environmental factors were investigated in Furong Creek from 2023 to 2024.This study focused on the analysis of the changes of nutrient concentrations and biomass of phytoplankton in autumn and spring within the same dry season in Furong Creek.Redundancy analysis was used to identify the key factors influencing the structure of phytoplankton communities.The MIKE 11 model was employed to simulate the hydrodynamic changes in the river.Combined with total nitrogen and permanganate index,a GAM model of phytoplankton diversity index and hydrodynamic factors was developed,and the change of phytoplankton diversity after the optimized layout of the cascade weirs was fitted.[Results]The result showed that the annual average value of Shannon-Wiener diversity index of phytoplankton in Furong Creek was 2.79,which was in a state of mild pollution.A total of 239 species from 95 genera in 8 phyla were identified.Among the phytoplankton,Chlorophyta was the dominant group throughout the year in Furong Creek,followed by Bacillariophyta and Cyanophyta.The cell abundance of phytoplankton ranged from 3.11 to 20.64 mg/L and from 0.23 to 6.31 mg/L in spring and autumn,which indicated a clear seasonal succession of phytoplankton community structure.Compared with autumn,the relative abundance of Cyanophyta significantly decreased in spring across the whole river section,while Chrysophyta and Dinophyta showed significant increase at some monitoring sites,leading to water bloom phenomenon and a noticeable decline in the diversity of phytoplankton.The dominant species in the water bodies throughout the year were Cyclotella catenata,Chlorella vulgaris,Scenedesmus bijuga,Scenedesmus quadricauda,Chroomonas acuta,Cryptomonas ovata,and Cryptomonas erosa.Redundancy analysis(RDA)showed that hydrodynamic factors(v,h)and water environmental factors(TN,COD_(Mn))were the main influencing factors of phytoplankton community structure.[Conclusion]The result show that the nutrient concentration,phytoplankton biomass,and density in Furong Creek in spring are significantly higher than in autumn.The GAM model,constructed by combining hydrodynamic and environmental factors,can effectively reflect the nonlinear relationship between phytoplankton diversity index and its driving factors.In spring,with an increase in nutrient concentration,the habitat conditions of low flow speed and high water depths formed by overflow weirs will lead to a decrease in the Shannon-Wiener index of phytoplankton and an intensified risk of eutrophication.However,a reasonable layout scheme of cascade weirs will improve the diversity of phytoplankton and reduce the risk of eutrophication in the river.The findings of this study can help deepen the understanding of the ecological and environmental effects of cascade weir construction in the river.展开更多
In the modal analysis and control of nonlinear dynamical systems,participation factors(PFs)of state variables with respect to a critical or selected mode serve as a pivotal tool for simplifying stability studies by fo...In the modal analysis and control of nonlinear dynamical systems,participation factors(PFs)of state variables with respect to a critical or selected mode serve as a pivotal tool for simplifying stability studies by focusing on a subset of highly influential state variables.For linear systems,PFs are uniquely determined by the mode’s composition and shape,which are defined by the system’s left and right eigenvectors,respectively.However,the uniqueness of other types of PFs has not been thoroughly addressed in literatures.This paper establishes sufficient conditions for the uniqueness of nonlinear PFs and five other PF variants,taking into account uncertain scaling factors in a mode’s shape and composition.These scaling factors arise from variations in the choice of physical units,which depend on the value ranges of real-world state variables.Understanding these sufficient conditions is essential for the correct application of PFs in practical stability analysis and control design.展开更多
Portfolio theory has been extensively studied and applied in finance.To determine the optimal portfolio weight under the global minimum variance strategy,it is necessary to estimate both the covariance matrix and its ...Portfolio theory has been extensively studied and applied in finance.To determine the optimal portfolio weight under the global minimum variance strategy,it is necessary to estimate both the covariance matrix and its inverse.However,the high dimensionality and heavy-tailed nature of financial data pose significant challenges to this estimation.In this study,we propose a method to estimate the Gini covariance matrix by introducing a low-rank and sparse correlation structure,as an alternative to the traditional sample covariance matrix.Our approach employs a factor model to capture the low-rank structure,combined with thresholding rules to achieve the final estimation.We demonstrate the consistency of our estimators and validate our approach through simulation experiments and empirical portfolio analyses.Simulation results show that our method is highly applicable across a variety of distributional scenarios.Furthermore,empirical portfolio analysis indicates that our method can construct portfolios with superior performance.展开更多
Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent im...Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.展开更多
For target tracking and localization in bearing-only sensor network,it is an essential and significant challenge to solve the problem of plug-and-play expansion while stably enhancing the accuracy of state estimation....For target tracking and localization in bearing-only sensor network,it is an essential and significant challenge to solve the problem of plug-and-play expansion while stably enhancing the accuracy of state estimation.This paper pro-poses a distributed state estimation method based on two-layer factor graph.Firstly,the measurement model of the bearing-only sensor network is constructed,and by investigating the observ-ability and the Cramer-Rao lower bound of the system model,the preconditions are analyzed.Subsequently,the location fac-tor graph and cubature information filtering algorithm of sensor node pairs are proposed for localized estimation.Building upon this foundation,the mechanism for propagating confidence mes-sages within the fusion factor graph is designed,and is extended to the entire sensor network to achieve global state estimation.Finally,groups of simulation experiments are con-ducted to compare and analyze the results,which verifies the rationality,effectiveness,and superiority of the proposed method.展开更多
OBJECTIVE Nuclear factor erythroid 2-related factor 2(Nrf2) is found to be ubiquitiously expressed in many tissues,and works as the key regulator against oxidative stress damage in cells and organs,which makes Nrf2 a ...OBJECTIVE Nuclear factor erythroid 2-related factor 2(Nrf2) is found to be ubiquitiously expressed in many tissues,and works as the key regulator against oxidative stress damage in cells and organs,which makes Nrf2 a widely concerned drug target.Recent research has identified that Nrf2 is involved in the pathology of Alzheimer disease(AD),whereas the mechanism is unknown.The purpose of this study is to figure out the role of Nrf2 in the pathologic process of AD through Nrf2-Keap1-ARE pathway and the effects of Keap1-Nrf2 inhibitor in AD mice models.METHODS Amyloid β^(1-42)(Aβ^(1-42))was injected into the bilateral hippocampus to induce the cognitive dysfunction in eight-week old male mice.The mice were treated with Keap1-Nrf2 inhibitor NXPZ of three doses as well as donepezil as a positive control by intragastric administration one time a day for one week.Several behavior tests were used to analyze the mice learning and memory ability.Additionally,we detected Nrf2 and Aβ in the plasma in mice with ELISA kits,as well as some factors related to oxidative stress in the hippocampus and cortex.The expression levels of Nrf2,Keap1,Tau and p-Tau were measured in the murine brain tissue with Western blotting.SH-SY5 Y cells were studied as an in vitro model to further clarify the mechanism.RESULTS The treatment of NXPZ ameliorated learning and memory dysfunction in AD mice in a dose-dependent manner,and the high dose group recovered better than the positive drug group.The plasma Nrf2 level was increased in a dose-dependent manner in the treatment groups;however,the plasma Aβ was decreased.What′ s more,superoxide dismutase(SOD) and glutathione reductase(GSSH) in the hippocampus and cortex were increased in the treatment group,while the malondialdehyde(MDA) was decreased,meaning that NXPZ treatment promoted expression of the anti-oxidative factors and inhibited the expression of the oxidative factors in the down-stream.Western blotting analysis of hippocampus and cortex showed up-regulated Nrf2,decreased Keap1 and decreased p-Tau in NXPZ treatment mice.In ex vivo experiments,when SH-SY5 Y cells were treated with Aβ,Nrf2 in the cytoplasm was increased,as well as the expression Nrf2 in the nuclear was decreased.The treatment of NXPZ increased nuclear Nrf2,decreased cytoplasm Nrf2,and decreased the expression of p-Tau.CONCLUSION Nrf2 has an important role in neuron function.Nrf2 activation by selective Keap1-Nrf2 inhibitor NXPZ may contribute to improve cognitive function in AD mice.The mechanism may be related to increased generation and release of Nrf2 induced by more disaggregation with Keap1,leading to more expression of anti-oxidative molecules to protect the damage caused by Aβ.These results indicates that Nrf2 may be a novel therapeutic target of AD and Keap1-Nrf2 inhibitor may be a novel medication for protecting the loss of learning and memory ability.展开更多
Dome structures have been used extensively for industrial,residential,and military infrastructure.Therefore,it is necessary to understand the damage risk potential for such structures for blast-resistant design consid...Dome structures have been used extensively for industrial,residential,and military infrastructure.Therefore,it is necessary to understand the damage risk potential for such structures for blast-resistant design considerations.This paper investigates the effect of blast load variability on the design value and the structural dynamic response.Therefore,the sources of uncertainty in the external blast load on dome structures were discussed firstly.Then based on the probabilistic blast load model for the dome,the rationality of a deterministic mass-increase safety method was assessed.It was found that previous deterministic design method cannot provide a consistent and sound assurance factor or reliability index on the entire dome roof.In addition,it was also proved that the assurance-based load method fails to ensure compliance with structural safety design standards on the dome roof when compared with the reliability-based blast method.A sensitivity analysis on the probabilistic blast load was conducted,and the results indicate that stand-off distance and explosive mass both act as dominant sources to influence the mean and variability of blast load.Therefore,based on the Latin hypercube sampling method,a reliability-based external blast load factor technique was proposed.This technique was further used to estimate structural damage levels of a single-layer reticulated dome under different reliability requirements,associated with a low,medium,and high level of protection grades for a specific explosion scenario,and it indicated that this technique can be useful in the building design to achieve a higher structural anti-explosion capacity.This study herein can serve as a reference for the calculation method of designed blast load.展开更多
OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like g...OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.展开更多
Aim Inducible nitric oxide synthase （iNOS） makes a great contribution to host defense and inflamma-tion. In many settings, lipopolysaccharide （LPS） induces iNOS expression through activation of the inhibitor of K...Aim Inducible nitric oxide synthase （iNOS） makes a great contribution to host defense and inflamma-tion. In many settings, lipopolysaccharide （LPS） induces iNOS expression through activation of the inhibitor of KB- α （IKB-α） -nuclear factor-KB （NF-KB） cascade, whereas interferon-γ （IFN-γ） acts through Janus kinase （ JAK）- signal transducer and activator of transcription 1 （ STAT1 ） signals. Heat shock factor 1 （ HSF1 ）, a major regulator of heat shock protein transcription, has been shown to regulate the production of pro-inflammatory cytokines such as tumor necrosis factor-α（TNF-α） and interleukin-6 （IL-6）. But it remains obscure whether and how HSF1 affects iNOS induction. Methods Western blot was used to measure the protein expression. The mRNA level was meas- ured by real time-PCR. Silence of HSF1 was achieved by small interfering RNA. Nitric oxide （NO） content and NF-KB binding activity were assayed by commercial kits. Chromatin immunoprecipitation （CHIP） was used to measure the binding activity of NF-KB and STAT1 to iNOS promoters. Results HSF1 inhibition or knockdown pre- vented the LPS- and/or IFN-γ-stimulated iNOS protein expression in cultured microglia. HSF1 inhibition blocked iNOS mRNA transcription. These inhibitory effects of HSF1 inhibition on iNOS expression were confirmed in brain tissues from endotoxemic mice. Further analysis showed that HSF1 inhibition had no effect on IKB-α degradation and NF-KB or STAT1 phosphorylation in LPS/IFN-γ-stimulated cells. The nuclear transport of active NF-KB or STAT1 was also not affected by HSF1 inhibition. But HSF1 inhibition reduced the binding of NF-KB and STAT1 to their DNA elements. In addition, HSF1 inhibition reduced NF-KB and STAT1 bindings to iNOS promoter inside the LPS/IFN-γ-stimulated cells. Conclusions This preventing effect of HSF1 inhibition on iNOS mRNA transcription presents the necessary role of HSF1 in iNOS induction.展开更多
In order to determine the slip plane of slope directly by the calculation results of strength reduction method, and analyze the influential factors of slope stability, a numerical model was established in plane strain...In order to determine the slip plane of slope directly by the calculation results of strength reduction method, and analyze the influential factors of slope stability, a numerical model was established in plane strain mode by FLAC3D for homogeneous soil slope, whose parameters were reduced until the slope reached the critical state. Then FISH program was used to get the location data of slip plane from displacement contour lines. Furthermore, the method to determine multiple slip planes was also proposed by setting different heights of elastic areas. The influential factors for the stability were analyzed, including cohesion, internal friction angle, and tensile strength. The calculation results show that with the increase of cohesion, failure mode of slope changes from shallow slipping to the deep slipping, while inclination of slip plane becomes slower and slipping volume becomes larger; with the increase of friction angle, failure mode of slope changes from deep slipping to shallow slipping, while slip plane becomes steeper and upper border of slip plane comes closer to the vertex of slope; the safety factor increases little and slip plane goes far away from vertex of slope with the increase of tensile strength.展开更多
OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ...OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.展开更多
In a wind-vehicle-bridge(WVB) system,there are various interactions among wind,vehicle and bridge.The mechanism for coupling vibration of wind-vehicle-bridge systems is explored to demonstrate the effects of fundament...In a wind-vehicle-bridge(WVB) system,there are various interactions among wind,vehicle and bridge.The mechanism for coupling vibration of wind-vehicle-bridge systems is explored to demonstrate the effects of fundamental factors,such as mean wind,fluctuating wind,buffeting,rail irregularities,light rail vehicle vibration and bridge stiffness.A long cable-stayed bridge which carries light rail traffic is regarded as a numerical example.Firstly,a finite element model is built for the long cable-stayed bridge.The deck can generally be idealized as three-dimensional spine beam while cables are modeled as truss elements.Vehicles are modeled as mass-spring-damper systems.Rail irregularities and wind fluctuation are simulated in time domain by spectrum representation method.Then,aerodynamic loads on vehicle and bridge deck are measured by section model wind tunnel tests.Eight vertical and torsional flutter derivatives of bridge deck are identified by weighting ensemble least-square method.Finally,dynamic responses of the WVB system are analyzed in a series of cases.The results show that the accelerations of the vehicle are excited by the fluctuating wind and the track irregularity to a great extent.The transverse forces of wheel axles mainly depend on the track irregularity.The displacements of the bridge are predominantly determined by the mean wind and restricted by its stiffness.And the accelerations of the bridge are enlarged after adding the fluctuating wind.展开更多
The safety factor of roof under deep high stress is a quantitative index for evaluating roof stability.Based on the failure mode of surrounding rock of stope roof,the mechanics model of goaf roof is constructed,and th...The safety factor of roof under deep high stress is a quantitative index for evaluating roof stability.Based on the failure mode of surrounding rock of stope roof,the mechanics model of goaf roof is constructed,and the internal force of roof is deduced by the theory of hingeless arch.The calculation method of roof safety factor(K)under the environment of deep mining is proposed in view of compression failure and shear failure of roof.The calculation formulas of shear safety factor(K1),compression safety factor(K2)and comprehensive safety factor(K)of roof are given.The influence of stope span and roof thickness on roof stability is considered in this paper.The results show that when the roof thickness remains constant,the roof safety factor decreases with the increasing of the stope span;when the stope span remains constant,the roof safety factor increases with the increasing of the roof thickness.The deep mining example shows that when the stope span is 30 m and the roof thickness is 10 m,the roof comprehensive safety factor is 1.12,which indicates the roof is in a stable state.展开更多
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30886).
文摘Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.
文摘[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore the nonlinear response relationship between phytoplankton community structure and its driving factors in spring and autumn in Furong Creek under the construction of cascade weirs.[Methods]The structure of phytoplankton communities and related environmental factors were investigated in Furong Creek from 2023 to 2024.This study focused on the analysis of the changes of nutrient concentrations and biomass of phytoplankton in autumn and spring within the same dry season in Furong Creek.Redundancy analysis was used to identify the key factors influencing the structure of phytoplankton communities.The MIKE 11 model was employed to simulate the hydrodynamic changes in the river.Combined with total nitrogen and permanganate index,a GAM model of phytoplankton diversity index and hydrodynamic factors was developed,and the change of phytoplankton diversity after the optimized layout of the cascade weirs was fitted.[Results]The result showed that the annual average value of Shannon-Wiener diversity index of phytoplankton in Furong Creek was 2.79,which was in a state of mild pollution.A total of 239 species from 95 genera in 8 phyla were identified.Among the phytoplankton,Chlorophyta was the dominant group throughout the year in Furong Creek,followed by Bacillariophyta and Cyanophyta.The cell abundance of phytoplankton ranged from 3.11 to 20.64 mg/L and from 0.23 to 6.31 mg/L in spring and autumn,which indicated a clear seasonal succession of phytoplankton community structure.Compared with autumn,the relative abundance of Cyanophyta significantly decreased in spring across the whole river section,while Chrysophyta and Dinophyta showed significant increase at some monitoring sites,leading to water bloom phenomenon and a noticeable decline in the diversity of phytoplankton.The dominant species in the water bodies throughout the year were Cyclotella catenata,Chlorella vulgaris,Scenedesmus bijuga,Scenedesmus quadricauda,Chroomonas acuta,Cryptomonas ovata,and Cryptomonas erosa.Redundancy analysis(RDA)showed that hydrodynamic factors(v,h)and water environmental factors(TN,COD_(Mn))were the main influencing factors of phytoplankton community structure.[Conclusion]The result show that the nutrient concentration,phytoplankton biomass,and density in Furong Creek in spring are significantly higher than in autumn.The GAM model,constructed by combining hydrodynamic and environmental factors,can effectively reflect the nonlinear relationship between phytoplankton diversity index and its driving factors.In spring,with an increase in nutrient concentration,the habitat conditions of low flow speed and high water depths formed by overflow weirs will lead to a decrease in the Shannon-Wiener index of phytoplankton and an intensified risk of eutrophication.However,a reasonable layout scheme of cascade weirs will improve the diversity of phytoplankton and reduce the risk of eutrophication in the river.The findings of this study can help deepen the understanding of the ecological and environmental effects of cascade weir construction in the river.
文摘In the modal analysis and control of nonlinear dynamical systems,participation factors(PFs)of state variables with respect to a critical or selected mode serve as a pivotal tool for simplifying stability studies by focusing on a subset of highly influential state variables.For linear systems,PFs are uniquely determined by the mode’s composition and shape,which are defined by the system’s left and right eigenvectors,respectively.However,the uniqueness of other types of PFs has not been thoroughly addressed in literatures.This paper establishes sufficient conditions for the uniqueness of nonlinear PFs and five other PF variants,taking into account uncertain scaling factors in a mode’s shape and composition.These scaling factors arise from variations in the choice of physical units,which depend on the value ranges of real-world state variables.Understanding these sufficient conditions is essential for the correct application of PFs in practical stability analysis and control design.
基金supported by the Postdoctoral Fellowship Program of CPSF(GZC20241651)the National Natural Science Foundation of China(12501391)the Natural Science Foundation of Anhui Province(2408085QA005).
文摘Portfolio theory has been extensively studied and applied in finance.To determine the optimal portfolio weight under the global minimum variance strategy,it is necessary to estimate both the covariance matrix and its inverse.However,the high dimensionality and heavy-tailed nature of financial data pose significant challenges to this estimation.In this study,we propose a method to estimate the Gini covariance matrix by introducing a low-rank and sparse correlation structure,as an alternative to the traditional sample covariance matrix.Our approach employs a factor model to capture the low-rank structure,combined with thresholding rules to achieve the final estimation.We demonstrate the consistency of our estimators and validate our approach through simulation experiments and empirical portfolio analyses.Simulation results show that our method is highly applicable across a variety of distributional scenarios.Furthermore,empirical portfolio analysis indicates that our method can construct portfolios with superior performance.
基金supported by the Hunan Provincial Science and Technology Major Special Fund(2021SK1020)the Natural Science Foundation of Hunan Province(2023JJ30948)+1 种基金the Health Commission of Hunan Province(202203014687)the International Medical Exchange Cardiovascular Multidisciplinary Integrated Thinking Research Foundation(Z-2016-23-2101-20),China.
文摘Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.
基金supported by the National Natural Science Foundation of China(62176214).
文摘For target tracking and localization in bearing-only sensor network,it is an essential and significant challenge to solve the problem of plug-and-play expansion while stably enhancing the accuracy of state estimation.This paper pro-poses a distributed state estimation method based on two-layer factor graph.Firstly,the measurement model of the bearing-only sensor network is constructed,and by investigating the observ-ability and the Cramer-Rao lower bound of the system model,the preconditions are analyzed.Subsequently,the location fac-tor graph and cubature information filtering algorithm of sensor node pairs are proposed for localized estimation.Building upon this foundation,the mechanism for propagating confidence mes-sages within the fusion factor graph is designed,and is extended to the entire sensor network to achieve global state estimation.Finally,groups of simulation experiments are con-ducted to compare and analyze the results,which verifies the rationality,effectiveness,and superiority of the proposed method.
基金National Natural Science Foundation of China(81703520).
文摘OBJECTIVE Nuclear factor erythroid 2-related factor 2(Nrf2) is found to be ubiquitiously expressed in many tissues,and works as the key regulator against oxidative stress damage in cells and organs,which makes Nrf2 a widely concerned drug target.Recent research has identified that Nrf2 is involved in the pathology of Alzheimer disease(AD),whereas the mechanism is unknown.The purpose of this study is to figure out the role of Nrf2 in the pathologic process of AD through Nrf2-Keap1-ARE pathway and the effects of Keap1-Nrf2 inhibitor in AD mice models.METHODS Amyloid β^(1-42)(Aβ^(1-42))was injected into the bilateral hippocampus to induce the cognitive dysfunction in eight-week old male mice.The mice were treated with Keap1-Nrf2 inhibitor NXPZ of three doses as well as donepezil as a positive control by intragastric administration one time a day for one week.Several behavior tests were used to analyze the mice learning and memory ability.Additionally,we detected Nrf2 and Aβ in the plasma in mice with ELISA kits,as well as some factors related to oxidative stress in the hippocampus and cortex.The expression levels of Nrf2,Keap1,Tau and p-Tau were measured in the murine brain tissue with Western blotting.SH-SY5 Y cells were studied as an in vitro model to further clarify the mechanism.RESULTS The treatment of NXPZ ameliorated learning and memory dysfunction in AD mice in a dose-dependent manner,and the high dose group recovered better than the positive drug group.The plasma Nrf2 level was increased in a dose-dependent manner in the treatment groups;however,the plasma Aβ was decreased.What′ s more,superoxide dismutase(SOD) and glutathione reductase(GSSH) in the hippocampus and cortex were increased in the treatment group,while the malondialdehyde(MDA) was decreased,meaning that NXPZ treatment promoted expression of the anti-oxidative factors and inhibited the expression of the oxidative factors in the down-stream.Western blotting analysis of hippocampus and cortex showed up-regulated Nrf2,decreased Keap1 and decreased p-Tau in NXPZ treatment mice.In ex vivo experiments,when SH-SY5 Y cells were treated with Aβ,Nrf2 in the cytoplasm was increased,as well as the expression Nrf2 in the nuclear was decreased.The treatment of NXPZ increased nuclear Nrf2,decreased cytoplasm Nrf2,and decreased the expression of p-Tau.CONCLUSION Nrf2 has an important role in neuron function.Nrf2 activation by selective Keap1-Nrf2 inhibitor NXPZ may contribute to improve cognitive function in AD mice.The mechanism may be related to increased generation and release of Nrf2 induced by more disaggregation with Keap1,leading to more expression of anti-oxidative molecules to protect the damage caused by Aβ.These results indicates that Nrf2 may be a novel therapeutic target of AD and Keap1-Nrf2 inhibitor may be a novel medication for protecting the loss of learning and memory ability.
基金supports from and Na-tional key research and development program of China(project No.2018YFC0705703)the National Natural Science Foundation of China(project No.51708521,51778183).
文摘Dome structures have been used extensively for industrial,residential,and military infrastructure.Therefore,it is necessary to understand the damage risk potential for such structures for blast-resistant design considerations.This paper investigates the effect of blast load variability on the design value and the structural dynamic response.Therefore,the sources of uncertainty in the external blast load on dome structures were discussed firstly.Then based on the probabilistic blast load model for the dome,the rationality of a deterministic mass-increase safety method was assessed.It was found that previous deterministic design method cannot provide a consistent and sound assurance factor or reliability index on the entire dome roof.In addition,it was also proved that the assurance-based load method fails to ensure compliance with structural safety design standards on the dome roof when compared with the reliability-based blast method.A sensitivity analysis on the probabilistic blast load was conducted,and the results indicate that stand-off distance and explosive mass both act as dominant sources to influence the mean and variability of blast load.Therefore,based on the Latin hypercube sampling method,a reliability-based external blast load factor technique was proposed.This technique was further used to estimate structural damage levels of a single-layer reticulated dome under different reliability requirements,associated with a low,medium,and high level of protection grades for a specific explosion scenario,and it indicated that this technique can be useful in the building design to achieve a higher structural anti-explosion capacity.This study herein can serve as a reference for the calculation method of designed blast load.
基金supported by National Natural Science Foundation of China(81502123 and81330081)Natural Science Foundation of Anhui Province(1308085QH130)Anhui Province Nature Science Foundation in University(KJ2014A119)
文摘OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.
文摘Aim Inducible nitric oxide synthase （iNOS） makes a great contribution to host defense and inflamma-tion. In many settings, lipopolysaccharide （LPS） induces iNOS expression through activation of the inhibitor of KB- α （IKB-α） -nuclear factor-KB （NF-KB） cascade, whereas interferon-γ （IFN-γ） acts through Janus kinase （ JAK）- signal transducer and activator of transcription 1 （ STAT1 ） signals. Heat shock factor 1 （ HSF1 ）, a major regulator of heat shock protein transcription, has been shown to regulate the production of pro-inflammatory cytokines such as tumor necrosis factor-α（TNF-α） and interleukin-6 （IL-6）. But it remains obscure whether and how HSF1 affects iNOS induction. Methods Western blot was used to measure the protein expression. The mRNA level was meas- ured by real time-PCR. Silence of HSF1 was achieved by small interfering RNA. Nitric oxide （NO） content and NF-KB binding activity were assayed by commercial kits. Chromatin immunoprecipitation （CHIP） was used to measure the binding activity of NF-KB and STAT1 to iNOS promoters. Results HSF1 inhibition or knockdown pre- vented the LPS- and/or IFN-γ-stimulated iNOS protein expression in cultured microglia. HSF1 inhibition blocked iNOS mRNA transcription. These inhibitory effects of HSF1 inhibition on iNOS expression were confirmed in brain tissues from endotoxemic mice. Further analysis showed that HSF1 inhibition had no effect on IKB-α degradation and NF-KB or STAT1 phosphorylation in LPS/IFN-γ-stimulated cells. The nuclear transport of active NF-KB or STAT1 was also not affected by HSF1 inhibition. But HSF1 inhibition reduced the binding of NF-KB and STAT1 to their DNA elements. In addition, HSF1 inhibition reduced NF-KB and STAT1 bindings to iNOS promoter inside the LPS/IFN-γ-stimulated cells. Conclusions This preventing effect of HSF1 inhibition on iNOS mRNA transcription presents the necessary role of HSF1 in iNOS induction.
基金Project(20060533071) supported by the Doctoral Program Foundation of Higher Education of ChinaProject (20060400264) supported by China Postdoctoral Science Foundation+1 种基金Project (50774093) supported by the National Natural Science Foundation of ChinaProject (1343-74236000014) supported by Graduate Student Innovation Foundation of Hunan Province, China
文摘In order to determine the slip plane of slope directly by the calculation results of strength reduction method, and analyze the influential factors of slope stability, a numerical model was established in plane strain mode by FLAC3D for homogeneous soil slope, whose parameters were reduced until the slope reached the critical state. Then FISH program was used to get the location data of slip plane from displacement contour lines. Furthermore, the method to determine multiple slip planes was also proposed by setting different heights of elastic areas. The influential factors for the stability were analyzed, including cohesion, internal friction angle, and tensile strength. The calculation results show that with the increase of cohesion, failure mode of slope changes from shallow slipping to the deep slipping, while inclination of slip plane becomes slower and slipping volume becomes larger; with the increase of friction angle, failure mode of slope changes from deep slipping to shallow slipping, while slip plane becomes steeper and upper border of slip plane comes closer to the vertex of slope; the safety factor increases little and slip plane goes far away from vertex of slope with the increase of tensile strength.
基金The project supported by National Natural Science Foundation of China(81302760)the Chinese Postdoctoral Science Foundation Project(2013M542510)
文摘OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.
基金Projects (U1334201,51525804) supported by the National Natural Science Foundation of ChinaProject (15CXTD0005) supported by the Sichuan Province Youth Science and Technology Innovation Team,China
文摘In a wind-vehicle-bridge(WVB) system,there are various interactions among wind,vehicle and bridge.The mechanism for coupling vibration of wind-vehicle-bridge systems is explored to demonstrate the effects of fundamental factors,such as mean wind,fluctuating wind,buffeting,rail irregularities,light rail vehicle vibration and bridge stiffness.A long cable-stayed bridge which carries light rail traffic is regarded as a numerical example.Firstly,a finite element model is built for the long cable-stayed bridge.The deck can generally be idealized as three-dimensional spine beam while cables are modeled as truss elements.Vehicles are modeled as mass-spring-damper systems.Rail irregularities and wind fluctuation are simulated in time domain by spectrum representation method.Then,aerodynamic loads on vehicle and bridge deck are measured by section model wind tunnel tests.Eight vertical and torsional flutter derivatives of bridge deck are identified by weighting ensemble least-square method.Finally,dynamic responses of the WVB system are analyzed in a series of cases.The results show that the accelerations of the vehicle are excited by the fluctuating wind and the track irregularity to a great extent.The transverse forces of wheel axles mainly depend on the track irregularity.The displacements of the bridge are predominantly determined by the mean wind and restricted by its stiffness.And the accelerations of the bridge are enlarged after adding the fluctuating wind.
基金Projects(51974135,51704094)supported by the National Natural Science Foundation of ChinaProject(2016YFC0600802)supported by the National Key Research and Development Program of ChinaProject(2020M672226)supported by the China Postdoctoral Science Foundation。
文摘The safety factor of roof under deep high stress is a quantitative index for evaluating roof stability.Based on the failure mode of surrounding rock of stope roof,the mechanics model of goaf roof is constructed,and the internal force of roof is deduced by the theory of hingeless arch.The calculation method of roof safety factor(K)under the environment of deep mining is proposed in view of compression failure and shear failure of roof.The calculation formulas of shear safety factor(K1),compression safety factor(K2)and comprehensive safety factor(K)of roof are given.The influence of stope span and roof thickness on roof stability is considered in this paper.The results show that when the roof thickness remains constant,the roof safety factor decreases with the increasing of the stope span;when the stope span remains constant,the roof safety factor increases with the increasing of the roof thickness.The deep mining example shows that when the stope span is 30 m and the roof thickness is 10 m,the roof comprehensive safety factor is 1.12,which indicates the roof is in a stable state.
