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The impact of hypoxia in hepatocellular carcinoma metastasis

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 33-41 doi: 10.1007/s11684-013-0301-3

摘要：

Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondar y growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis.

关键词： hypoxia     hepatocellular carcinoma (HCC)     metastasis     hypoxia-inducible factor (HIF)    

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Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K

LI Yanhua, BI Zhigang

《医学前沿（英文）》 2007年 第1卷 第1期   页码 79-86 doi: 10.1007/s11684-007-0016-4

摘要： The aim of this research was to explore the effects and signaling pathway of ultraviolet-B (UVB) irradiation on the expression of hypoxia-inducible factor 1α (HIF-1α) and transferrin receptor (TfR). HIF-1α protein was measured by Western blot method. Expressions of epidermal growth factor receptor (EGFR), phosphor-EGF-R and TfR after UVB irradiation were determined with flow cytometry. After UVB irradiation, mRNA levels of HIF-1α and TfR were detected by real time-PCR. Results showed that compared with control groups, UVB was able to induce HIF1α and TfR protein expression in a dose- and time-dependent manner in HaCat cells (<0.05). TfR mRNA was expressed in a dose-dependent manner and reached a peak at the 8th hour in HaCat cells (<0.05) whereas HIF-1α mRNA expression was not affected by UVB treatment (>0.05). The EGFR/PI3K/AKT signaling pathway was required for the induction of HIF-1α and TfR expression induced by UVB. UVB induced activation of EGFR in HaCat cells and EGFR regulated expression of TfR and HIF-1α. EGFR (-/-) MEF did not increase the HIF1 expression following UVB irradiation (>0.05). In contrast, EGFR (+/+) MEF strongly enhanced HIF1α expression after UVB irradiation (<0.05). PD153035, a selective inhibitor of EGFR tyrosine kinase, inhibited the TfR protein expression in UVB-treated cells in a dose-dependent manner (P<0.05). PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1? and TfR expressions induced by UVB (P<0.05). The DEC1 (-/-) Ha-Cat cells did not increase their TfR and HIF-1α expressions following UVB irradiation (>0.05). In contrast, DEC1 (+/+) HaCat cells strongly enhanced TfR and HIF-1? protein expression after UVB irradiation (P<0.05). We conclude that UVB induces TfR and HIF-1αexpressions via EGFR/PI3K/AKT/DEC1 signaling pathway.
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Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of

Bin YANG MS , Xianglin YUAN , Yanmei ZOU , Qingsong XI , Guoxian LONG , Qiang FU , Guangyuan HU MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 303-308 doi: 10.1007/s11684-009-0060-3

摘要： The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α (HIF-1α) were investigated. The Hela cells were divided into three groups, namely, H (non-transfected Hela cells), H (pGenesil-1 empty plasmid-transfected Hela cells), and H (HIF-1α-shRNA plasmid-transfected Hela cells), and were cultured under hypoxia (1% O) and normoxia for 48h. The expression of HIF-1α, E-cadherin, β-catenin, and actin was detected using Western blot. The scratch test and the invasion assay were applied to examine the invasion in each group. The expression of HIF-1α, E-cadherin, and β-catenin in tumor grafts was assayed immunohistochemically. Western blot results revealed that the bands of HIF-1α, E-cadherin, β-catenin, and actin proteins were detected in the H and H groups under hypoxia for 48h. The expression of E-cadherin, β-catenin, and actin was detected in the H group under hypoxia for 48h, and normoxia. In the H, H, and H groups under normoxia, and the H group under hypoxia for 48h, no expression of HIF-1α was detectable. The scratch test showed that the invasive ability in the H group was significantly alleviated. Immunohistochemically, it was found that there was a significant difference in the expression of HIF-1α, E-cadherin, and β-catenin between the H and H groups (<0.05), but the difference was not significant between the H and H groups. It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins (E-cadherin, β-catenin, and actin) depend on HIF-1α.

关键词： hypoxia     actin     β     -catenin     E-cadherin     invasion    

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Expression of inducible nitric oxide synthase in trophoblasts and deciduas in early medical abortion

Geqing XIA, Chaoying WU

《医学前沿（英文）》 2009年 第3卷 第2期   页码 216-219 doi: 10.1007/s11684-009-0028-3

摘要： The purpose of this study was to investigate the expression of inducible nitric oxide synthase in trophoblasts and deciduas in early medical abortion, and study the relationship of medical abortion through mifepristone and inducible nitric oxide synthase (iNOS) in early pregnancy. Expression of iNOS in trophoblasts and deciduas was detected by both hybridization and immunohistochemical assay in 40 patients (experimental group); the positive expression of iNOS was represented by number density (N/S) and positive unit (Pu) using computer color magic image analysis system (CMIAS). All results were compared with that obtained from vacuum aspiration. In the experimental group, N/S and Pu in trophoblasts were 0.120 ± 0.010 and 15.3 ± 2.6, respectively, while in the control group, they were 0.021 ± 0.003 and 3.1 ± 0.5, respectively, and there were significant differences between the two groups. By immunohistochemical assay, N/S and Pu were 0.090 ± 0.010, 10.24 ± 1.55 0.016 ± 0.002, 1.26 ± 0.33 in the trophoblasts of the two groups; there were also significant differences between the two groups. There were lower iNOS expressions in deciduas by in situ hybridization and immunohistochemical assay, and the difference between the two groups was not significant.It was concluded that mifepristone induced medical abortion through the expression of iNOS in trophoblasts but not in deciduas.

关键词： mifepristone     inducible nitric oxide synthase     early pregnancy     placental immunity    

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Hypoxia-induced activity loss of a photo-responsive microtubule inhibitor azobenzene combretastatin A4

Yang An, Chao Chen, Jundong Zhu, Pankaj Dwivedi, Yanjun Zhao, Zheng Wang

《化学科学与工程前沿（英文）》 2020年 第14卷 第5期   页码 880-888 doi: 10.1007/s11705-019-1864-6

摘要： The conformation-dependent activity of azobenzene combretastatin A4 (Azo-CA4) provides a unique approach to reduce the side-effects of chemotherapy, due to the light-triggered conformation transition of its azobenzene moiety. Under hypoxic tumor microenvironment, however, the high expression of azoreductase can reduce azobenzene to aniline. It was postulated that the Azo-CA4 might be degraded under hypoxia, resulting in the decrease of its anti-tumor activity. The aim of this study was to verify such hypothesis in HeLa cells . The quantitative drug concentration analysis shows the ratiometric formation of degradation end-products, confirming the bioreduction of Azo-CA4. The tubulin staining study indicates that Azo-CA4 loses the potency of switching off microtubule dynamics under hypoxia. Furthermore, the cell cycle analysis shows that the ability of Azo-CA4 to induce mitotic arrest is lost at low oxygen content. Therefore, the cytotoxicity of Azo-CA4 is compromised under hypoxia. In contrast, combretastatin A4 as a positive control maintains the potency to inhibit tubulin polymerization and break down the nuclei irrespective of light irradiation and oxygen level. This work highlights the influence of hypoxic tumor microenvironment on the anti-tumor potency of Azo-CA4, which should be considered during the early stage of designing translational Azo-CA4 delivery systems.

关键词： hypoxia     microtubule inhibitor     drug delivery     azo-combretastatin A4     photo-responsive    

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Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured

YANG Yingzhong, MA Lan, GE Rili, FAN Wenhong, ZHU Lingling, ZHAO Tong, WU Yan, FAN Ming

《医学前沿（英文）》 2008年 第2卷 第3期   页码 239-243 doi: 10.1007/s11684-008-0045-7

摘要： Internal standards are critical for quantitative RNA analyses. Housekeeping genes are often used as internal standards with the assumption that their expression levels remain relatively constant in different experimental conditions. In this study, four commonly used housekeeping genes, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ?-actin, 28S rRNA and 18S rRNA were selected to test whether this assumption is tenable under hypoxic conditions. We tested the RNA expression level of these four genes in different hypoxic conditions. Rats subjected to acute hypoxia for 2 hours were used for tissue detection. Primary cultured neural stem cells from E13 fetal rats were treated with 3% O or 10% O for 24 hours for experiments. In both experiments, expression levels of 28S rRNA and 18S rRNA were constant, independent of hypoxia types. However, expression levels of GAPDH and ?-actin were all changed in all kinds of hypoxic conditions. In particular, the mRNA expression level of GAPDH was increased by 43.4% under 3% O hypoxic conditions. These results suggest that 18S rRNA and 28S rRNA are reliable internal controls for comparative analyses of transcription under hypoxia. GAPDH appears particularly unfavorable for this purpose in hypoxic conditions.

关键词： Glyceraldehyde-3-phosphate dehydrogenase     comparative     constant     unfavorable     independent    

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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a     FOXM1     transcription factor     cancer     drug resistance     tumorigenesis    

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LSSVM-based approach for refining soil failure criteria and calculating safety factor of slopes

Shiguo XIAO; Shaohong LI

《结构与土木工程前沿（英文）》 2022年 第16卷 第7期   页码 871-881 doi: 10.1007/s11709-022-0863-8

摘要： The failure criteria of practical soil mass are very complex, and have significant influence on the safety factor of slope stability. The Coulomb strength criterion and the power-law failure criterion are classically simplified. Each one has limited applicability owing to the noticeable difference between calculated predictions and actual results in some cases. In the work reported here, an analysis method based on the least square support vector machine (LSSVM), a machine learning model, is purposefully provided to establish a complex nonlinear failure criterion via iteration computation based on strength test data of the soil, which is of more extensive applicability to many problems of slope stability. In particular, three evaluation indexes including coefficient of determination, mean absolute percentage error, and mean square error indicate that fitting precision of the machine learning-based failure criterion is better than those of the linear Coulomb criterion and nonlinear power-law criterion. Based on the proposed LSSVM approach to determine the failure criterion, the limit equilibrium method can be used to calculate the safety factor of three-dimensional slope stability. Analysis of results of the safety factor of two three-dimensional homogeneous slopes shows that the maximum relative errors between the proposed approach and the linear failure criterion-based method and the power-law failure criterion-based method are about 12% and 7%, respectively.

关键词： slope stability     safety factor     failure criterion     least square support vector machine    

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lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

《医学前沿（英文）》 2023年 第17卷 第2期   页码 317-329 doi: 10.1007/s11684-022-0931-4

摘要： Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

关键词： lncR-GAS5     miR-193-5p     splicing factor SRSF10     autophagy     atherogenesis    

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The calculation of equivalence factor for ecological footprints in China: a methodological note

Moucheng LIU,Wenhua LI,Dan ZAHNG,Ning SU

《环境科学与工程前沿（英文）》 2015年 第9卷 第6期   页码 1015-1024 doi: 10.1007/s11783-014-0670-0

摘要： The Ecological Footprint (EF), a physical indicator to measure the extent of humanity’s use of natural resources, has gained much attention since it was first used by Wackernagel and Rees in 1996. In order to appraise land area types with different levels of productivity, they introduced the concept of an equivalence factor. This relates to the average primary biomass productivities of different types of land (i.e. arable land, pasture, forest, water/fishery, built-up land and fossil energy land) to the regional average primary biomass productivity of all land types in a given year. Hence, the equivalence factor is an important parameter in the EF model and it directly affects the reliability of all results. Thus, this article calculates equivalence factors on the national and provincial levels in China based on Net Primary Production (NPP) from MODIS 1 km data in 2008. Firstly, based on the Light Utility Efficiency and CASA model, the NPP of different biologically productive lands of China and of different provinces was calculated. Secondly, China’s equivalence factor for 6 land area types was calculated based on NPP: arable land and built-up land has an equivalence factor of 1.71, forest and fossil energy land has a factor of 1.41, pasture has a factor of 0.44 and water/fishery 0.35; Finally, the equivalence factor of 6 land area types in different provinces was also calculated. The NPP of each ecosystem type varies along with the equivalence factor in different provinces. However, the ranking of the equivalence factors in different provinces remain the same, with that of arable land being the largest, and the water/fishery being the smallest.

关键词： ecological footprint     equivalence factor     net primary production     biological capacity     land types    

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A practical multi-lane factor model of bridges based on multi-truck presence considering lane load disparities

《结构与土木工程前沿（英文）》 2021年 第15卷 第4期   页码 877-894 doi: 10.1007/s11709-021-0756-2

摘要： Many bridge design specifications consider multi-lane factors (MLFs) a critical component of the traffic load model. Measured multi-lane traffic data generally exhibit significant lane disparities in traffic loads over multiple lanes. However, these disparities are not considered in current specifications. To address this drawback, a multi-coefficient MLF model was developed based on an improved probabilistic statistical approach that considers the presence of multiple trucks. The proposed MLF model and approach were calibrated and demonstrated through an example site. The model sensitivity analysis demonstrated the significant influence of lane disparity of truck traffic volume and truck weight distribution on the MLF. Using the proposed approach, the experimental site study yielded MLFs comparable with those directly calculated using traffic load effects. The exclusion of overloaded trucks caused the proposed approach, existing design specifications, and conventional approach of ignoring lane load disparity to generate comparable MLFs, while the MLFs based on the proposed approach were the most comprehensive. The inclusion of overloaded trucks caused the conventional approach and design specifications to overestimate the MLFs significantly. Finally, the benefits of the research results to bridge practitioners were discussed.

关键词： bridges     multi-lane factor     traffic load     lane load disparity     multi-truck presence     weigh-in-motion data    

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Numerical investigation of the influence of kinetics and shape factor on barium sulfate precipitation

Zheng WANG, Zai-Sha MAO, Chao YANG, Qinghua ZHANG, Jingcai CHENG

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 272-281 doi: 10.1007/s11705-009-0023-x

摘要： The effect of kinetics and shape factor on barium sulfate precipitation in a continuous stirred tank has been investigated numerically through solving the standard momentum and mass transport equations in combination with the moment equations for crystal population balance. The numerical method was validated with the literature data. The simulated results include the distribution of the local supersaturation ratio in the reactor, the mean crystal size, and the coefficient of variation. The simulation results show that the value of shape factor used in the model affected greatly the mean crystal size and the moments of the crystal size distribution. The influence of the kinetic expressions on the simulation is also analyzed. It is important to investigate the relationship of the shape factor with the precipitator type and other operation conditions to obtain reliable simulation results and suitable kinetic equations of crystal nucleation and growth rates.

关键词： stirred tank     numerical simulation     precipitation     shape factor     crystal kinetics    

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The formation mechanism and the influence factor of residual stress in machining

null

《机械工程前沿（英文）》 2014年 第9卷 第3期   页码 265-269 doi: 10.1007/s11465-014-0311-0

摘要：

Residual stresses generated in cutting process have important influences on workpiece performance. The paper presents a method of theoretical analysis in order to explicate the formation mechanism of residual stresses in cutting. An important conclusion is drawn that the accumulated plastic strain is the main factor which determines the nature and the magnitude of surface residual stresses in the workpiece. On the basis of the analytical model for residual stress, a series of simulations for residual stress prediction during cutting AISI 1045 steel are implemented in order to obtain the influences of cutting speed, depth of cut and tool edge radius on surface residual stress in the workpiece. And these influences are explained from the perspective of formation mechanism of residual stress in cutting. The conclusions have good applicability and can be used to guide the parameters selection in actual production.

关键词： residual stress     analytical model     strain     plastic     cutting parameter    

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Endogenous tissue factor pathway inhibitor in vascular smooth muscle cells inhibits arterial thrombosis

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 403-409 doi: 10.1007/s11684-017-0522-y

摘要：

Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPIFlox mice crossbred with Sma–Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis. The mice with deleted TFPI in VSMCs (TFPISma) reproduced viable offspring. Plasma TFPI concentration was reduced 7.2% in the TFPISma mice compared with TFPIFlox littermate controls. Plasma TFPI concentration was also detected in the TFPITie2 (mice deleted TFPI in endothelial cells and cells of hematopoietic origin) mice. Plasma TFPI concentration of the TFPITie2 mice was 80.4% lower (P<0.001) than that of the TFPIFlox mice. No difference in hemostatic measures (PT, APTT, and tail bleeding) was observed between TFPISma and TFPIFlox mice. However, TFPISma mice had increased ferric chloride–induced arterial thrombosis compared with TFPIFlox littermate controls. Taken together, these data indicated that endogenous TFPI from VSMCs inhibited ferric chloride–induced arterial thrombosis without causing hemostatic effects.

关键词： arterial thrombosis     conditional knockout mice     tissue factor pathway inhibitor     vascular smooth muscle cells    

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Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 25-30 doi: 10.1007/s11684-013-0244-8

摘要：

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

关键词： FGF21     metabolism     pharmacology     physiology     clinical relevance    

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标题 作者 时间 类型 操作

The impact of hypoxia in hepatocellular carcinoma metastasis

null

期刊论文

Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K

LI Yanhua, BI Zhigang

期刊论文

Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of

Bin YANG MS , Xianglin YUAN , Yanmei ZOU , Qingsong XI , Guoxian LONG , Qiang FU , Guangyuan HU MM ,

期刊论文

Expression of inducible nitric oxide synthase in trophoblasts and deciduas in early medical abortion

Geqing XIA, Chaoying WU

期刊论文

Hypoxia-induced activity loss of a photo-responsive microtubule inhibitor azobenzene combretastatin A4

Yang An, Chao Chen, Jundong Zhu, Pankaj Dwivedi, Yanjun Zhao, Zheng Wang

期刊论文

Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured

YANG Yingzhong, MA Lan, GE Rili, FAN Wenhong, ZHU Lingling, ZHAO Tong, WU Yan, FAN Ming

期刊论文

Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

期刊论文

LSSVM-based approach for refining soil failure criteria and calculating safety factor of slopes

Shiguo XIAO; Shaohong LI

期刊论文

lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

期刊论文

The calculation of equivalence factor for ecological footprints in China: a methodological note

Moucheng LIU,Wenhua LI,Dan ZAHNG,Ning SU

期刊论文

A practical multi-lane factor model of bridges based on multi-truck presence considering lane load disparities

期刊论文

Numerical investigation of the influence of kinetics and shape factor on barium sulfate precipitation

Zheng WANG, Zai-Sha MAO, Chao YANG, Qinghua ZHANG, Jingcai CHENG

期刊论文

The formation mechanism and the influence factor of residual stress in machining

null

期刊论文

Endogenous tissue factor pathway inhibitor in vascular smooth muscle cells inhibits arterial thrombosis

null

期刊论文

Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

期刊论文