Transforming growth factor beta-1 upregulates glucose transporter 1 and glycolysis through canonical and noncanonical pathways in hepatic stellate cells

BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transforming growth factor-β1(TGF-β1)induces aerobic glycolysis and is a driving factor for metabolic reprogramming.The occurrence of glycolysis depends on a high glucose uptake level.Glucose transporter 1(GLUT1)is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism,thus affecting cell proliferation and growth.However,little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs.AIM To investigate the mechanisms of action of GLUT1,TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis.METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue.A Seahorse extracellular flux(XF)analyzer was used to examine changes in aerobic glycolytic flux,lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation.The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothersagainst-decapentaplegic-homolog 2/3(Smad2/3)signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase(PI3K)/AKT signaling pathways.In addition,GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs.Finally,a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis.RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues.In addition,immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins,indicating that GLUT1 expression was related to the development of liver fibrosis.TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad,p38 MAPK and P13K/AKT signaling pathways.The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression.GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration.A GLUT1 inhibitor was administered in a mouse model of liver fibrosis,and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis.CONCLUSION TGF-β1 induces GLUT1 expression in HSCs,a process related to liver fibrosis progression.In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs.In addition,in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.

O6-methylguanine DNA methyltransferase is upregulated in malignant transformation of gastric epithelial cells via its gene promoter DNA hypomethylation

BACKGROUND O_(6)-methylguanine-DNA methyltransferase(MGMT)is a suicide enzyme that repairs the mispairing base O_(6)-methyl-guanine induced by environmental and experimental carcinogens.It can transfer the alkyl group to a cysteine residue in its active site and became inactive.The chemical carcinogen N-nitroso compounds(NOCs)can directly bind to the DNA and induce the O_(6)-methylguanine adducts,which is an important cause of gene mutation and tumorigenesis.However,the underlying regulatory mechanism of MGMT involved in NOCs-induced tumorigenesis,especially in the initiation phase,remains largely unclear.AIM To investigate the molecular regulatory mechanism of MGMT in NOCs-induced gastric cell malignant transformation and tumorigenesis.METHODS We established a gastric epithelial cell malignant transformation model induced by N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)or N-methyl-N-nitroso-urea(MNU)treatment.Cell proliferation,colony formation,soft agar,cell migration,and xenograft assays were used to verify the malignant phenotype.By using quantitative real-time polymerase chain reaction(qPCR)and Western blot analysis,we detected the MGMT expression in malignant transformed cells.We also confirmed the MGMT expression in early stage gastric tumor tissues by qPCR and immunohistochemistry.MGMT gene promoter DNA methylation level was analyzed by methylation-specific PCR and bisulfite sequencing PCR.The role of MGMT in cell malignant transformation was analyzed by colony formation and soft agar assays.RESULTS We observed a constant increase in MGMT mRNA and protein expression in gastric epithelial cell malignant transformation induced by MNNG or MNU treatment.Moreover,we found a reduction of MGMT gene promoter methylation level by methylation-specific PCR and bisulfite sequencing PCR in MNNG/MNU-treated cells.Inhibition of the MGMT expression by O_(6)-benzylguanine promoted the MNNG/MNU-induced malignant phenotypes.Overexpression of MGMT partially reversed the cell malignant transformation process induced by MNNG/MNU.Clinical gastric tissue analysis showed that MGMT was upregulated in the precancerous lesions and metaplasia tissues,but downregulated in the gastric cancer tissues.CONCLUSION Our finding indicated that MGMT upregulation is induced via its DNA promoter hypomethylation.The highly expressed MGMT prevents the NOCs-induced cell malignant transformation and tumorigenesis,which suggests a potential novel approach for chemical carcinogenesis intervention by regulating aberrant epigenetic mechanisms.

DIFFERENCES IN EXPRESSION AND REGULATION BETWEEN TRANSFORMED CELLS OF THE HUMAN GASTRIC CARCINOMA ONCOGENE Ha-ras AND THE UNTRANSFORMED PARENT CELLS

An Ha-ras oncogene was isolated from a cell line of gastric carcinoma called BGE-823 in order to elucidate genetic control and the influence of DNA sequences. The oncogene was cloned and identified as a single nucleotide substitution of thymine for guanine in the 12th codon through the sequencing of its first axon. We compared the differences of expression and regulation between the transformed Ha-ras cells and untransformed parent cells. Data indicated that the expression of Ha-ras in the transformed cells was five-fold higher than in the untransformed cells and that the Ha-ras gene in the former was hypersensitive toward DNase I. In addition, a nuclear protein of 35 kilodaltons bound strongly to the 2.5 Kb fragment located upstream of the 6.6 Kb Ha-ras gene and contained a CC rich region. These results suggest that there might be another mechanism of activation for the ras gene besides point mutation.

Conflicts in Defining Data Ownership in China’s Digital Transformation and the Regulatory Path

China is aggressively pursuing digital transformation,and data,alike labor,technology,capital,and knowledge,has become as a crucial factor of production.Digital transformation is accelerating the emergence of a data-intensive society,and the ensuing difficulties of balancing freedom and responsibility,openness and security,as well as free sharing and legal regulation are posing new challenges to national and social governance.Among these challenges,defining data ownership,the social disorder and anomie brought about by the unclear definition of data ownership,and data ownership regulatory path are new propositions that need to be urgently addressed in this data-intensive society.This paper systematically explains the theoretical meaning and practical value of data ownership through a literature review on the analysis of domestic and foreign scholars as well as research think tanks,compares the differences and inherent conflicts between the definition of data ownership by the government,enterprises,and society in China,thoroughly compares the definition standards of the European Union,the United States,and Japan,and on this basis,discusses the formation of a definition of data ownership that meets the requirements of China’s digital transformation.

Industrial wastes applications for alkalinity regulation in bauxite residue: A comprehensive review

Bauxite residue is a highly alkaline material generated from the production of alumina in which bauxite is dissolved in caustic soda.Approximately 4.4 billion tons of bauxite residues are either stockpiled or landfilled,creating environmental risks either from the generation of dust or migration of filtrates.High alkalinity is the critical factor restricting complete utilization of bauxite residues,whilst the application of alkaline regulation agents is costly and difficult to apply widely.For now,current industrial wastes,such as waste acid,ammonia nitrogen wastewater,waste gypsum and biomass,have become major problems restricting the development of the social economy.Regulation of bauxite residues alkalinity by industrial waste was proposed to achieve‘waste control by waste’with good economic and ecological benefits.This review will focus on the origin and transformation of alkalinity in bauxite residues using typical industrial waste.It will propose key research directions with an emphasis on alkaline regulation by industrial waste,whilst also providing a scientific reference point for their potential use as amendments to enhance soil formation and establish vegetation on bauxite residue disposal areas(BRDAs)following large-scale disposal.

Alkalinity stabilization behavior of bauxite residue:Ca-driving regulation characteristics of gypsum

Alkaline anions,include CO3^2–,HCO3^–,Al(OH)4^–,OH^–,continuously released from bauxite residue(BR),will cause a potential disastrous impact on surrounding environment.The composition variation of alkaline anions,alkaline phase transformation pathway,and micro-morphological transition characteristics during the gypsum addition were investigated in an attempt to understand alkalinity stabilization behavior.Results demonstrated that alkaline anions stabilization degree in leachates can reach approximately 96.29%,whilst pH and alkalinity were reduced from 10.47 to 8.15,47.39 mmol/L to 2 mmol/L,respectively.During the alkalinity stabilization,chemical regulation behavior plays significant role in driving the co-precipitation reaction among the critical alkaline anions(CO3^2–,HCO3^–,Al(OH)4^–,OH^–),with calcium carbonate(CaCO3))being the most prevalent among the transformed alkaline phases.In addition,XRD and SEM-EDX analyses of the solid phase revealed that physical immobilization behavior would also influence the stability of soluble alkali and chemical bonded alkali due to released Ca^2+from gypsum which aggregated the clay particles and stabilized them into coarse particles with a blocky structure.These findings will be beneficial for effectively regulating strong alkalinity of BR.

Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

Agrobacterium tumefaciens-mediated transformation of Eucalyptus urophylla clone BRS07-01

Genetic transformation is becoming routine for engineering specific traits in important clones of recalcitrant species such as Eucalyptus;however,the efficiency is still low for most species,so many researchers still use seeds instead of clones as initial explants.This work aimed to develop a genetic transformation protocol,based on a highly efficient in vitro organogenesis protocol,for an Eucalyptus urophylla clone selected in our breeding program.Plant growth regulators were evaluated for indirect organogenesis and rooting.In a two-step protocol,the combination of callus induction media supplemented with 0.5 μM thidiazuron+0.5 μM naphthaleneacetic acid(NAA)and shoot induction media supplemented with 5.0 μM benzylaminopurine+1.0 lM NAA allowed up to 85.6%shoot formation with more shoots per explants when compared with other concentrations.Transgenic plants expressing the uidA gene were obtained using Agrobacterium tumefaciens and selected for kanamycin resistance.A RAPD analysis was used to check for somaclonal variation.In tests using 11 RAPD primers,we did not observe somaclonal variation in the in vitro stages evaluated.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.

Non-Euclidean Geometry and Regulated Characteristics of Limited Capacity Power Supply

The restriction of load power, two-valued regulation characteristic, and interference of several loads are observed in power supply systems with a limited capacity of voltage sources. In this paper, the definition of regime in an invariant form through different parameters, of changes of transformation ratio and voltage load is grounded for these circuits with two loads. The approach for interpretation of changes or ＂kinematics＂ of load regime is presented by using the conformal and hyperbolic plane. To simplify the task and reveal the basic moments of influence of the limited source power, the static regulation characteristics and idealized models of voltage converters are considered. Geometrical interpretation of a simplified model of multichannel power supply system allows basing the definition of operating regime parameters. Results can be useful for electric circuit theory education and for voltage coordinated control of given loads. Non-Euclidean geometry is a new mathematical apparatus in the electric circuit theory, adequately interprets ＂kinematics＂ of circuit, and provides a validation for the introduction and definition of the proposed concepts. From the methodological point, the presented approach is applied for a long time in other scientific domains, as mechanics and biology.

教育数字化转型中的算法权力及其规制

依托框架优势、机器优势和嵌入优势的全新算法,将会随着数字平台的搭建、数据资源的挖掘、“人–机”交互的设计,由单纯的计算工具向事务运行规则转变,进而演变为教育数字化转型中不容回避的权力议题。教育数字化转型中的算法权力既有益于管理风险、规范行为和辅助决策,也可能由于自身的局限以及它与教育之间的冲突,导致教育的风险异化、行为降格和决策失衡。要将算法权力规制到安全、可靠的“笼子”之中,除借助算法目标的教育审查、算法设计的教育解释、算法运行的教育监管、算法应用的教育鉴别、算法信息的教育备案、算法责任的教育认定,以构建从背景、过程到结果的规范机制;还应诉诸教育之于算法的祛魅、平衡与扬弃,以凸显“入乎其内却又出乎其外”的制衡思想。

环境规制、数字化转型与绿色技术创新——来自中国工业企业的数据分析

在工业强国战略日益深化的背景下,环境规制对工业企业绿色技术创新的影响已成为研究的热点问题。利用2007—2021年中国A股工业上市公司为研究样本的有效数据,构建非线性模型进行实证研究,研究发现:环境规制强度与工业企业绿色技术创新呈“U形”关系,环境规制在低强度范围内抑制了绿色技术创新,而在达到最佳环境强度范围时则促进了绿色技术创新。数字化转型对工业企业绿色技术创新有正向影响。数字化转型是环境规制强度促进绿色技术创新关系的重要途径,政府环境规制驱动企业数字化转型进而作用于绿色技术创新。异质性检验发现,环境规制对绿色技术创新的影响在东西部地区、政府补贴程度高和非国有工业企业中的影响更为显著。未来应适度加强环境规制强度,同时通过企业数字化转型,持续推动工业企业绿色技术创新,构建绿色低碳循环发展经济体系。

中国省域环境规制与科技创新耦合协调发展研究

环境规制与科技创新耦合协调发展能为实现经济增长与生态文明提供强有力的支撑。该文构建环境规制与科技创新水平评价指标体系,利用耦合协调度模型测算2009—2020年中国30个省域环境规制与科技创新的耦合协调度,并对耦合协调度的时空分布格局进行分析。结果表明:研究期内中国30个省域环境规制与科技创新的耦合协调度整体偏低,尚未达到良性耦合协调发展状态,但呈现上升趋势,增幅呈现“西高东低”特征;各地区耦合协调度发展不均衡,整体呈现“东高西低、南高北低”的空间分布格局,高水平耦合协调区域逐渐从东部沿海向内陆扩张;依据协调等级和特征将各省域划分为创新主动型、技术进步型、环境约束型、传统被动型和创新滞后型,并提出环境规制应结合地区创新能力实施差异化的区域政策等建议。

电力电子变压器参与配电网调压调频的应用研究

为提升配电网的稳定性,该文提出利用配电网电力电子变压器对配电网的电压和频率进行调节。通过电力电子变压器输入级进行配电网无功功率调节,利用母线电压下垂特性提出无功调节方法,并引入无功电流反馈以提高配电网电压质量和稳定性;同时,通过电力电子变压器输出级控制负载电压以调节配网有功功率,作为一次调频储备负载,从而在频率暂态期间减小频率偏差。通过对基于配电网电力电子变压器的调压调频控制方法进行实验验证,所提控制策略能改善配电网电压和频率质量,有效提升配电网的稳定性。

“多言少行”的数字化转型会影响公司碳排放吗?

以制造业和重污染上市公司2009—2020年的数据为样本,从不同角度实证研究公司“多言少行”数字化转型对碳排放的影响。研究发现:“多言少行”数字化转型会显著促进公司碳排放增加;相比于“少言少行”和“少言多行”,多“言”的数字化转型有更明显的增加作用;相比于其他过程,“多言少行”对生产过程的碳排放正向影响更为明显;环境规制显著抑制了“多言少行”对碳排放的促进作用。进一步分析发现,“多言少行”对碳排放的作用受到“言”增多和“行”减少的共同影响,提高政府补助、降低融资约束、管理层短视上升在其中起到了机制作用。研究结论有助于认识到“多言少行”数字化转型的机会主义和潜在风险,为监管部门规范数字化转型信息披露提供依据。

生产性服务数智化对农业绿色全要素生产率的影响——兼论政府环境规制的调节作用

为推进农业农村现代化,亟需以生产性服务业数智化为契机,对传统农业生产方式进行全方位改造,提高农业综合生产能力。在理论阐述农业生产性服务数智化影响农业绿色全要素生产率(AGTFP)的内在机制基础上,构建包含金融服务、科技信息服务和商贸流通服务三部分的农业生产性服务数智化综合评价指标体系,并通过回归模型对2014—2020年我国29个省(区、市)的面板数据进行实证检验。结果表明:生产性服务数智化改造对AGTFP水平的提升具有显著的促进作用。具体来讲,金融服务和商贸流通服务的数智化改造对AGTFP的影响呈现当期有效的特征,而科技信息服务数智化改造在较长的时间内仍可以保持对AGTFP的显著促进效应;农业生产性服务数智化促进作用存在明显的区域异质性,从强到弱依次为粮食主产区、粮食产销平衡区、粮食主销区;政府环境治理能够强化农业生产性服务数智化对AGTFP的影响。基于此,应大力推进现代信息技术对传统农业生产方式的改造,构建以科技信息服务为基础,金融服务、商贸流通服务为引领,拉动农业绿色全要素生产率提升的长效增长机制。

数字政策对城市经济韧性的影响研究

基于2013—2022年30个省份面板数据,利用PSM-DID模型分析了不同城市数字政策制定对城市经济韧性影响,同时分析了环境规制和产业数字化转型在数字政策促进城市经济韧性提升过程中的作用.研究结果表明:数字政策执行对城市经济韧性具有显著的正向效应,在沿海地区中的效应要强于在内陆地区中的效应.产业数字化转型在数字政策对城市经济韧性的影响中起着中介作用,且存在一定的非线性效应;在较高的产业数字化转型水平下,数字政策促进城市经济韧性提升的效应更为显著;环境规制在数字政策促进城市经济韧性提升的过程中发挥着动态调节作用,即在环境规制执行前期,数字政策不利于城市经济韧性提升,而在环境规制执行后期,数字政策对城市经济韧性起着积极的促进作用.

双芯移相变压器在主动配电网电压和潮流调控中的应用分析

双芯移相变压器可以有效控制线路电压和潮流,优化潮流分布,提高电网电能质量。针对分布式电源的高比例接入造成的主动配电网电压波动和偏差问题,以及对潮流大小、方向和均衡度的影响,文章研究了双芯移相变压器的拓扑结构和工作原理;然后分析了串联变压器和励磁变压器的具体结构和作用,梳理了移相变压器分别应用于电压调节和潮流控制时的档位控制策略;最后基于MATLAB/Simulink建立了详细的仿真模型,研究了双芯移相变压器的电压调节效果,并对双线路并联、两路电源并联供电、多路电源并联供电三种应用场景下的潮流控制效果作了比较。仿真结果表明,双芯移相变压器可以在有限的档位内将线路电压控制在允许范围;与双线路并联、多路电源并联供电应用场景相比,两路电源并联供电时的潮流均衡效果最好,潮流偏差最小,本研究为双芯移相变压器的广泛应用提供了参考。

东道国双重环境规制对企业绿色转型的影响研究

在突出绿色发展理念和双循环发展战略背景下,绿色转型已成为中国跨国投资企业高质量发展的必由之路。驱动跨国投资企业绿色转型的因素不仅包括本国的制度和文化,而且包括东道国的环境规制。以2012—2021年中国A股上市公司为研究样本,实证检验东道国双重环境规制对企业绿色转型的影响。研究结果表明:东道国的正式环境规制和非正式环境规制均会对企业绿色转型产生倒U型影响;政府环保补助可以提升企业对东道国正式环境规制的容忍度,但是会抑制企业在东道国环境规制压力下的绿色转型程度;东道国环境规制主要通过海外收入的利润反馈机制和海外技术逆向溢出机制影响企业的绿色转型;企业内部的数字化程度和组织冗余水平会促进企业绿色转型,东道国正式环境规制对企业绿色转型的影响更为显著。从国际经济循环视角研究东道国制度对企业绿色转型的影响,对优化企业跨国投资经营和政府政策完善具有重要现实意义。

番泻叶苷A对糖尿病肾病大鼠足细胞自噬的影响

目的探究番泻叶苷A(sennoside A,SA)对糖尿病肾病(diabetic nephropathy,DN)大鼠足细胞自噬及上皮-间质转化(EMT)的影响及可能的作用机制。方法随机选择10只雄性Wistar大鼠作为正常组,剩余大鼠尾静脉注射55 mg·kg^(−1)链脲佐菌素(streptozotocin,STZ)诱导DN大鼠模型。将成模大鼠随机分为模型组、SA低剂量组、SA高剂量组及贝那普利组,每组10只。SA低剂量组、SA高剂量组大鼠每日分别灌胃给予SA 40、80 mg·kg^(−1),贝那普利组大鼠每日灌服给予盐酸贝那普利10 mg·kg^(−1),模型组及正常组大鼠每日灌服等量生理盐水,连续给药21 d。检测24 h尿白蛋白(albumin,Alb)含量、大鼠空腹血糖(fasting blood glucose,FBG)、血肌酐(serum creatinine,Scr)和血尿素氮(blood urea nitrogen,BUN)水平;染色观察肾组织学变化;透射电镜观察肾脏组织自噬体形成情况;蛋白印迹法(Western blotting)检测肾组织中微管相关蛋白1轻链3(icrotubule associated protein 1 light chain 3,LC3)、Bcl-2相互作用蛋白1(Bcl-2 interacting protein 1,Beclin-1)、E-钙黏蛋白(E-cadherin,E-cad)、波形蛋白(vimentin,Vim)、沉默信息调节因子1(silencing information regulator 1,Sirt1)和肾病蛋白nephrin蛋白的相对表达水平。结果与正常组比较,其他4组大鼠24 h Alb含量、FBG及Scr、BUN水平升高,肾小球和肾小管发生病理损伤,胶原纤维及糖原明显沉积,肾小球系膜及基底膜增厚,肾组织中自噬体数量减少,LC3Ⅱ/LC3Ⅰ比值、Beclin-1、E-cad、nephrin及Sirt1蛋白的相对表达量降低,Vim蛋白的相对表达量升高(P<0.05);与模型组比较,3个给药组大鼠24 h Alb含量、FBG及Scr、BUN水平降低,肾小球和肾小管病理损伤情况呈不同程度减轻,胶原纤维及糖原沉积减弱,肾小球系膜及基底膜增厚情况改善,自噬体数量增加,LC3Ⅱ/LC3Ⅰ比值、Beclin-1、E-cad、nephrin及Sirt1蛋白的相对表达量升高,Vim蛋白的相对表达量降低(P<0.05);SA低剂量组、SA高剂量组及贝那普利组对DN大鼠的作用效果逐渐增强(P<0.05)。结论SA可改善DN大鼠肾功能障碍,其作用机制可能与激活Sirt通路进而促进足细胞自噬并减轻EMT有关。