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
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
For regional ecological management,it is important to evaluate the quality of ecosystems and analyze the underlying causes of ecological changes.Using the Google Earth Engine(GEE)platform,the remote sensing ecological...For regional ecological management,it is important to evaluate the quality of ecosystems and analyze the underlying causes of ecological changes.Using the Google Earth Engine(GEE)platform,the remote sensing ecological index(RSEI)was calculated for the Lijiang River Basin in Guangxi Zhuang Autonomous Region for 1991,2001,2011,and 2021.Spatial autocorrelation analysis was employed to investigate spatiotemporal variations in the ecological environmental quality of the Lijiang River Basin.Furthermore,geographic detectors were used to quantitatively analyze influencing factors and their interaction effects on ecological environmental quality.The results verified that:1)From 1991 to 2021,the ecological environmental quality of the Lijiang River Basin demonstrated significant improvement.The area with good and excellent ecological environmental quality in proportion increased by 19.69%(3406.57 km^(2)),while the area with fair and poor ecological environmental quality in proportion decreased by 10.76%(1860.36 km^(2)).2)Spatially,the ecological environmental quality of the Lijiang River Basin exhibited a pattern of low quality in the central region and high quality in the periphery.Specifically,poor ecological environmental quality characterized the Guilin urban area,Pingle County,and Lingchuan County.3)From 1991 to 2021,a significant positive spatial correlation was observed in ecological environmental quality of the Lijiang River Basin.Areas with high-high agglomeration were predominantly forests and grasslands,indicating good ecological environmental quality,whereas areas with low-low agglomeration were dominated by cultivated land and construction land,indicating poor ecological environmental quality.4)Annual average precipitation and temperature exerted the most significant influence on the ecological environmental quality of the basin,and their interactions with other factors had the great influence.This study aimed to enhance understanding of the evolution of the ecological environment in the Lijiang River Basin of Guangxi Zhuang Autonomous Region and provide scientific guidance for decision-making and management related to ecology in the region.展开更多
Roof disaster has always been an important factor restricting coal mine safety production.Acidic effect can reform the rock mass structure to weaken the macroscopic strength characteristics,which is an effective way t...Roof disaster has always been an important factor restricting coal mine safety production.Acidic effect can reform the rock mass structure to weaken the macroscopic strength characteristics,which is an effective way to control the hard limestone roof.In this study,the effects of various factors on the reaction characteristics and mechanical properties of limestone were analyzed.The results show that the acid with stronger hydrogen production capacity after ionization(pK_(a)<0)has more prominent damage to the mineral grains of limestone.When pKa increases from−8.00 to 15.70,uniaxial compressive strength and elastic modulus of limestone increase by 117.22%and 75.98%.The influence of acid concentration is manifested in the dissolution behavior of mineral crystals,the crystal defects caused by large-scale acid action will lead to the deterioration of limestone strength,and the strength after 15%concentration reformation can be reduced by 59.42%.The effect of acidification time on limestone has stages and is the most obvious in the initial metathesis reaction stage(within 60 min).The key to the strength damage of acidified limestone is the participation of hydrogen ions in the reaction system.Based on the analytic hierarchy process method,the influence weights of acid type,acid concentration and acidification time on strength are 24.30%,59.54% and 16.16%,respectively.The research results provide theoretical support for the acidification control of hard limestone roofs in coal mines.展开更多
Marine structures are frequently subjected to repeated impact loadings,resulting in failure of the structures,even causing serious accidents.The analytical expressions of dimensionless permanent deflection and impact ...Marine structures are frequently subjected to repeated impact loadings,resulting in failure of the structures,even causing serious accidents.The analytical expressions of dimensionless permanent deflection and impact force of a metal beam based on maximal normal yield surface are derived by membrane factor method(MFM),then the results are compared with repeated impact tests.It can be found that the solutions based on MFM are between the upper and lower bounds,and very close to the results of the repeated impact tests,indicating the theoretical model proposed can predict the plastic responses of the metal beam accurately.What’s more,the influences of impact location and boundary condition on the dynamic responses of the beam subjected to repeated impacts are determined.Results show that,as the distance of impact location from the middle span of the beam increases,the permanent deflection decreases,while the impact force increases.Meanwhile,the influences of impact location enhance as the impact number increases.When the permanent deflection is smaller than the thickness,the effect of boundary condition on the plastic responses is significant.However,when the deflection is larger than the thickness,the beam will be like a string and only axial force works,resulting in little influence of boundary condition on the plastic responses of the beam.展开更多
Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production...Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.展开更多
Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic ...Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance.The NAC proteins are crucial and plant-specific transcription factors(TFs)that are involved in cotton growth,development,and stress responses.The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible.Based on cotton genomic data,genome-wide identification and analyses have revealed potential functions of cotton NAC genes.Here,we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought,salt,and Verticillium wilt-related stresses,as well as leaf senescence and the development of fibers,xylem,and glands.The detailed regulatory network of NAC proteins in cotton is also elucidated.Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation,participate in several biological processes by interacting with related proteins,and regulate the expression of downstream genes.Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance.This review elucidates the latest findings on the functions and regulation of cotton NAC proteins,broadens our understanding of cotton NAC TFs,and lays a fundamental foundation for further molecular breeding research in cotton.展开更多
Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum c...Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.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
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.
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supported by the Guangxi Natural Science Foundation(2020GXNSFAA297266)Doctoral Research Foundation of Guilin University of Technology(GUTQDJJ2007059)Guangxi Hidden Metallic Mineral Exploration Key Laboratory。
文摘For regional ecological management,it is important to evaluate the quality of ecosystems and analyze the underlying causes of ecological changes.Using the Google Earth Engine(GEE)platform,the remote sensing ecological index(RSEI)was calculated for the Lijiang River Basin in Guangxi Zhuang Autonomous Region for 1991,2001,2011,and 2021.Spatial autocorrelation analysis was employed to investigate spatiotemporal variations in the ecological environmental quality of the Lijiang River Basin.Furthermore,geographic detectors were used to quantitatively analyze influencing factors and their interaction effects on ecological environmental quality.The results verified that:1)From 1991 to 2021,the ecological environmental quality of the Lijiang River Basin demonstrated significant improvement.The area with good and excellent ecological environmental quality in proportion increased by 19.69%(3406.57 km^(2)),while the area with fair and poor ecological environmental quality in proportion decreased by 10.76%(1860.36 km^(2)).2)Spatially,the ecological environmental quality of the Lijiang River Basin exhibited a pattern of low quality in the central region and high quality in the periphery.Specifically,poor ecological environmental quality characterized the Guilin urban area,Pingle County,and Lingchuan County.3)From 1991 to 2021,a significant positive spatial correlation was observed in ecological environmental quality of the Lijiang River Basin.Areas with high-high agglomeration were predominantly forests and grasslands,indicating good ecological environmental quality,whereas areas with low-low agglomeration were dominated by cultivated land and construction land,indicating poor ecological environmental quality.4)Annual average precipitation and temperature exerted the most significant influence on the ecological environmental quality of the basin,and their interactions with other factors had the great influence.This study aimed to enhance understanding of the evolution of the ecological environment in the Lijiang River Basin of Guangxi Zhuang Autonomous Region and provide scientific guidance for decision-making and management related to ecology in the region.
基金Project(2021YFC2902102)supported by the National Key Research and Development Program of ChinaProject(52374142)supported by the National Natural Science Foundation of ChinaProject(JSTU-2022-066)supported by the Young Talent Support Project of Jiangsu Association for Science and Technology,China。
文摘Roof disaster has always been an important factor restricting coal mine safety production.Acidic effect can reform the rock mass structure to weaken the macroscopic strength characteristics,which is an effective way to control the hard limestone roof.In this study,the effects of various factors on the reaction characteristics and mechanical properties of limestone were analyzed.The results show that the acid with stronger hydrogen production capacity after ionization(pK_(a)<0)has more prominent damage to the mineral grains of limestone.When pKa increases from−8.00 to 15.70,uniaxial compressive strength and elastic modulus of limestone increase by 117.22%and 75.98%.The influence of acid concentration is manifested in the dissolution behavior of mineral crystals,the crystal defects caused by large-scale acid action will lead to the deterioration of limestone strength,and the strength after 15%concentration reformation can be reduced by 59.42%.The effect of acidification time on limestone has stages and is the most obvious in the initial metathesis reaction stage(within 60 min).The key to the strength damage of acidified limestone is the participation of hydrogen ions in the reaction system.Based on the analytic hierarchy process method,the influence weights of acid type,acid concentration and acidification time on strength are 24.30%,59.54% and 16.16%,respectively.The research results provide theoretical support for the acidification control of hard limestone roofs in coal mines.
文摘Marine structures are frequently subjected to repeated impact loadings,resulting in failure of the structures,even causing serious accidents.The analytical expressions of dimensionless permanent deflection and impact force of a metal beam based on maximal normal yield surface are derived by membrane factor method(MFM),then the results are compared with repeated impact tests.It can be found that the solutions based on MFM are between the upper and lower bounds,and very close to the results of the repeated impact tests,indicating the theoretical model proposed can predict the plastic responses of the metal beam accurately.What’s more,the influences of impact location and boundary condition on the dynamic responses of the beam subjected to repeated impacts are determined.Results show that,as the distance of impact location from the middle span of the beam increases,the permanent deflection decreases,while the impact force increases.Meanwhile,the influences of impact location enhance as the impact number increases.When the permanent deflection is smaller than the thickness,the effect of boundary condition on the plastic responses is significant.However,when the deflection is larger than the thickness,the beam will be like a string and only axial force works,resulting in little influence of boundary condition on the plastic responses of the beam.
文摘Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.
基金supported by the Young Scientists Fund of the National Natural Science Foundation of China(32101797)Central Public-interest Scientific Institution Basal Research Fund(No.1610162023020)。
文摘Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance.The NAC proteins are crucial and plant-specific transcription factors(TFs)that are involved in cotton growth,development,and stress responses.The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible.Based on cotton genomic data,genome-wide identification and analyses have revealed potential functions of cotton NAC genes.Here,we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought,salt,and Verticillium wilt-related stresses,as well as leaf senescence and the development of fibers,xylem,and glands.The detailed regulatory network of NAC proteins in cotton is also elucidated.Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation,participate in several biological processes by interacting with related proteins,and regulate the expression of downstream genes.Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance.This review elucidates the latest findings on the functions and regulation of cotton NAC proteins,broadens our understanding of cotton NAC TFs,and lays a fundamental foundation for further molecular breeding research in cotton.
基金supported by the Natural Science Foundation of Hunan Province(2023JJ60087)the Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK53501),China。
文摘Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.
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.
