MiR-183-5p promotes the progression of non-small cell lung cancer through targeted regulation of FOXO1

Objective To investigate miR-183-5p targeting to forkhead box protein O1(FOXO1)and its corresponding effect on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of non-small cell lung cancer(NSCLC)cells.Methods NSCLC tissues and adjacent normal tissues from 60 patients with NSCLC adenocarcinoma were obtained via pathological biopsy or intraoperative resection.Several cell lines were cultured in vitro,including the human normal lung epithelial cell line BEAS-2B and human NSCLC cell lines A549,SPCA-1,PC-9,and 95-D.miR-183-5p and FOXO1 mRNA expression in tissues and cells were detected by qRT-PCR;the corresponding correlations in NSCLC tissues were analyzed using the Pearson test,and the relationship between miR-183-5p expression and clinicopathological parameters was analyzed.The miR-183-5p-mediated regulation of FOXO1 was verified by bioinformatics prediction alongside double luciferase,RNA-binding protein immunoprecipitation(RIP)assay,and pull-down experiments.A549 cells were divided into control,anti-miR-NC,anti-miR-183-5p,miR-NC,miR-183-5p,miR-183-5p+pcDNA3.1,and miR-183-5p+pcDNA3.1-FOXO1 groups.Cell proliferation,invasion,migration,apoptosis,and cell cycle distribution were detected using an MTT assay,clone formation assay,Transwell assay,scratch test,and flow cytometry,respectively.The expression of EMT-related proteins in the cells was analyzed by western blotting.The effect of miR-185-3p silencing on the development of transplanted tumors was detected by analyzing tumor formation in nude mice.Results miR-183-5p expression was significantly higher in NSCLC tissues and cells than in adjacent normal tissues,whereas FOXO1 mRNA expression was significantly down-regulated.There was a significant negative correlation between miR-183-5p and FOXO1 mRNA in NSCLC tissues(P<0.05).Additionally,the expression of miR-183-5p was significantly correlated with tumor size,tumor differentiation,and tumor-node-metastasis stage in patients with NSCLC(P<0.05).miR-183-5p targeted and inhibited FOXO1 expression.Compared to the anti-miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the anti-miR-183-5p group,whereas the protein expression of E-cadherin andα-catenin and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion were significantly lower in the anti-miR-183-5p group(P<0.05).Compared to the miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells in the miR-183-5p group were significantly higher,whereas the E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly lower;furthermore,the frequency of colony formation and invasion were significantly higher in the miR-183-5p group(P<0.05).Compared with the miR-183-5p+pcDNA3.1 group,the OD value,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group,whereas E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion was significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group(P<0.05).Overall,silencing miR-185-3p inhibited the growth of transplanted tumors and promoted FOXO1 expression.Conclusion Overexpression of miR-183-5p can inhibit apoptosis and promote the proliferation,migration,invasion,and EMT,of NSCLC cells by down-regulating FOXO1 expression.

A Novel Cellular Autoaggregative Developmentally CRP Regulated Behaviour Generates Massively Chondrule-Like Formations over Surface of Old <i>Escherichia coli</i>K-12 Macrocolony Biofilms

How Escherichia coli bacteria develop a particular colonial, 3-D biofilm morphological pattern is still a poorly understood process. Recently, we reported a new E. coli K-12 morphotype exhibited by old macrocolonies described as volcano-like. The formative developmental process of this morphotype has been presented as a suitable experimental model for the study of 3D patterning in macrocolony biofilms. Here, we report the optical microscopy observations and genetic analysis that have unveiled the existence of a novel autoaggregative behaviour which generates massive lumpiness over the surface of the volcano-like macrocolonies. These lumpy formations are generated by the autoaggregation and strong interaction of tightly packed bacterial cells in structures with a chondrule-like appearance which give the colony’s surface its characteristic microscopic lumpy phenotype. Furthermore, they exhibit different levels of maturation from the edge to the center of the colony. Hence, its generation appears to follow a spatiotemporal program of development during the macrocolony’s morphogenesis. Interestingly, the agar’s hardness influences the morphology exhibited by these formations, with high agar concentration (1.5%, 15 g/L) suppressing its development. This new auto-aggregative E. coli’s behaviour does not require the activity of the biofilm master regulator CsgD, the adhesiveness of flagella, pili type 1, adhesin Ag43, β-1,6-N-acetyl-D-glucosamine polymer-PGA, cellulose or colanic acid, but it is under glucose repression and the control of cAMP receptor protein (CRP). The possible physiological role of these chondrule-like formations in the adaptability of the colony to different stressful environmental conditions is discussed.

Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p

BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Synthesis,Crystal Structure and Plant Growth Regulatory Activity of 1-(3-Amino-[1,2,4]triazol-1-yl)-3,3-dimethyl-butan-2-one

The title compound 1-（3-amino-[1,2,4]triazol-1-yl）-3,3-dimethyl-butan-2-one（3） was synthesized by Hofmann-alkylation reaction of 1-chloro-3,3-dimethyl-butan-2-one（1） and ~1H-[1,2,4]triazol-3-ylamine（2） with equal amount of K_2CO_3 as acid acceptor. The structure of compound 3 was characterized by ~1H NMR, 13 C NMR, HRMS and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic system, space group P21/n with a = 5.7227（8）, b = 27.924（4）, c = 6.2282（7） ？, β = 101.892（11）°, V = 973.9（2） ？~3, Z = 4, T = 180.00（10） K, μ（MoKα） = 0.087 mm^（-1）, Dc = 1.243 g/cm^3, 3832 reflections measured（3.648≤θ≤26.022°）, 1916 unique reflections（Rint = 0.0359, Rsigma = 0.0572） used in all calculations. The final R = 0.0557（I 〉 2σ（I）） and w R = 0.1276（all data）. Bioassay showed that 3 displayed excellent activity as plant growth regulator with inducing lateral root formation and enhancing primary root elongation at 0.27 mmol/L（50 ppm） in soybeen（He Feng-50）. Good water solubility was found with 50 mg in 1 m L of water. Therefore, application of 3 in agriculture is more environmentally friendly due to cosolvent-free condition, and results in improved abiotic-stress tolerance by affecting the root growth. And furthermore, it can be used as a precursor to investigate the function of regulating plant root growth.

circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

不同抵押约束机制下的房地产市场调控政策效应——基于NK-DSGE模型的分析

抵押约束机制对于房地产乃至宏观经济均具有显著影响。构建包含房地产与商业银行的NK-DSGE模型,考察一期抵押约束(IAC)机制与多期抵押约束(GKS)机制下的房地产市场调控政策效果。结果表明:无论是出于稳定实际房价还是出于经济增长的考虑,限购等引起负向房地产偏好冲击的政策、紧缩性货币政策以及增加公积金贷款数量的短期LTV政策,在GKS机制下均具有比IAC机制下更好的效果;基于脉冲响应比较研究发现,在IAC机制下调整首付比例具有更明显的政策效果;无论在IAC机制下还是在GKS机制下,房地产市场均是货币政策应当盯住的目标,监管当局应推行具有反周期性特征的宏观审慎政策工具,以实现房地产市场和物价的稳定。

论金融宏观调控--再为中国金融立论

一国的货币供给量取决于进入市场中流通的商品和能够反映商品使用价值和价值的商品价格量的总和。必须遵循货币的供给是有限的、能够计量的,而不是任意的、不能计量的。货币供给量是有限的,靠货币供给量着力于金融宏观调控的力量是有限的。“央行行为的哲理”是金融宏观调控的艺术和必修课。经济社会的重大变化表现为:人口老龄化——社会保障巨额增加——国内储蓄与投资难以均衡;贫富差距拉大,要迈过“中等收入陷阱”,造就中等收入阶层;中美之争以及关联度成为全球经济问题的核心。金融宏观调控关注的基点是:要关注国民实际收入的变化,要关注区域经济的建设和发展,要把社会就业始终作为金融宏观调控的首要目标,要密切关注财政信贷收支的综合平衡,要关注经济周期和金融周期。建立现代中国央行制度,就要提高对金融市场变迁的敏感度和适应能力,增强央行独立性。

从茫然、应然到实然--论宏观经济调控的形成

我国市场经济宏观调控的形成,是中国当代经济史中值得研究的问题之一。狭义宏观调控论认为宏观调控是指政府运用财政货币政策调节社会总供需,限于宏观层面,目标是实现充分就业、价格水平稳定、经济增长和国际收支平衡。以狭义的宏观经济调控概念为基准,可从经济思想转变、微观经济基础、市场化进程、政府经济管理体制以及宏观调控工具箱的构建,对中国市场经济宏观调控的形成过程进行梳理。具体过程如下:1976—1991年为体制改革探索的茫然期,1992—1996年为确立改革目标后的应然向实然过渡期,1997年之后初步形成宏观经济调控的实然期。研究表明,中国市场经济的宏观调控初步形成于亚洲金融危机之后的1997—1999年。

宏观审慎框架下的银行资本监管及其最优规则--基于“双重道德风险”的动态随机一般均衡分析

随着我国宏观审慎政策框架的落实和供给侧结构性改革的深化,如何进一步完善商业银行的资本监管,在提升金融支持实体经济能力的同时,增强银行体系韧性、防范系统性风险,已成为需要重点关注的问题。本文基于"双重道德风险"的动态随机一般均衡模型,分析了宏观审慎框架下的银行资本监管及其最优规则。研究发现:逆周期银行资本要求体现了宏观审慎监管理念,具有稳定宏观经济的"压舱石"作用。作为事前成本,其可约束银行过度放贷,抑制金融失衡的风险积累;作为风险补偿工具,其可提高银行吸收损失和应对冲击的能力,缓解传统资本监管的顺周期性,避免纯粹资产缩减造成的深度经济衰退。在实体经济冲击下,宏观审慎银行资本监管与货币政策存在矛盾冲突,需要加强二者政策的协调配合;而在金融冲击下,宏观审慎银行资本监管与货币政策之间相互补充、彼此强化。从社会福祉角度看,货币政策与宏观审慎银行资本监管协调配合时,社会福利改善最显著。鉴此,本文提出健全宏观审慎框架下的银行资本监管,不断完善资本补充机制及强化货币政策与银行资本监管的协调与配合等政策建议。

土地宏观调控的IS-LM模型建立及其分析

在宏观经济模型IS-LM的基础上,引入土地的供应量变量,建立了土地宏观调控的IS-LM模型,分析土地政策对宏观经济的影响及其调控效果。结果表明,土地供应量越大,均衡收入水平也越大;较大的土地边际投资倾向、较高的土地自发性支出都对均衡收入有促进作用。

宏观政策分析模型E-CPI

基于经济学中的GDP-CPI模型,研究了用电量与价格指数的E-CPI模型。此模型可以每月动态分析经济运行状况,研究需要采取什么样的财政政策及货币政策等实现宏观调控,为政府提供决策参考。采用E-CPI模型分析了2011年我国经济运行的走势及宏观政策的调控效果。根据政府提出的经济发展目标,研究了2012年财政政策及货币政策的走势,并提出相关建议以供参考。

经济法与经济发展方式的转变--转变经济发展方式的法治保障

加快转变经济发展方式需要法治保障，这对我国的法治尤其是经济法治提出了更高的要求。为此，要把握好调控监管、市场经济与法治之间的辨证关系，在坚持政府为主导、市场在资源配置中发挥基础性作用的同时，摈弃政府动辄使用直接行政手段和“运动式”调控的做法，将其能动的调控监管纳入问责制，不能任其脱法。规划和产业政策法、财税法、金融法、资源和环境法等都是转变经济发展方式所需依托的主要法律制度。

lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn’s disease

BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.

海上交通网络模型微-宏观模拟

应用排队论及网络技术建立了海上交通计算机模型,该模型的输入为港口的交通设计方案,输出为该港口的交通参数。在模拟过程中,详细记录船舶在港口及其附近水域内的各种活动,统计出与航行安全、时间、效率等有关的交通参数。从而可以直接在交通模型上研究、验证交通管制方案的的可行性,修改交通方案的管制参数,以便选定最佳方案。

宏观审慎管理政策对货币政策实施效果的影响--以计提逆周期资本缓冲为例

2008年的金融危机暴露了金融业缺乏系统性监管的缺陷,引起监管当局对商业银行宏观审慎管理和系统性风险防范的深刻思考,2010年版巴塞尔协议据此提出各国监管当局应构建逆周期监管框架。本文按照巴塞尔协议Ⅲ建议的方法,利用H-P滤波法模拟计提2008-2018年间中国银行体系逆周期缓冲资本,讨论了若实施逆周期资本缓冲政策可能对货币政策稳定、经济增长以及通货膨胀产生的影响。结果表明,提取逆周期缓冲资本有助于减少货币政策波动性,提高货币、信贷与GDP的匹配度,从而减少对经济稳定的冲击,降低通货膨胀风险,一定范围内可对货币政策的制定与实施起到自动调节作用,有助于控制系统性风险。

Macro-/micro-coupling regulation of nanoporous metals via vapor phase alloying-dealloying

Nanoporous metals with bicontinuous ligament-channel structure are of great importance in catalysis,electro-catalysis,actuation and energy storage and conversion.However,the intrinsic brittleness of nanoporous metals has always been the“Achilles heel”that impedes their practical applications.Utilizing the vapor pressure difference of metals,herein we propose a flexible and general vapor phase alloying(VPA)-dealloying strategy to fabricate nanoporous layers supported on the substrates with the same element.By adjusting the VPA time and temperature,the thickness and microstructure control over nanoporous layers can be realized by combining with diverse dealloying methods.Besides,various metals including Ag,Au,Cu,Co and Ni with different macro sizes and shapes can be fabricated into nanoporous structures through this method.More importantly,the greatly improved tensile ductility owing to the nanoporous layersubstrate structure and well enhanced catalytic performance for hydrogen evolution reaction of the as-fabricated nanoporous metals signify great potentials of the VPA-dealloying strategy for practical applications.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Decreased miR-325-5p Contributes to Visceral Hypersensitivity Through Post-transcriptional Upregulation of CCL2 in Rat Dorsal Root Ganglia

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of mi RNA-325-5 p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of mi RNA-325-5 p in a rat model of chronic visceral pain.This model was induced by neonatal colonic inflammation(NCI). In adulthood, NCI led to a significant reduction in the expression of mi RNA-325-5 p in colon-related dorsal root ganglia(DRGs), starting to decrease at the age of4 weeks and being maintained to 8 weeks. Intrathecal administration of mi RNA-325-5 p agomir significantly enhanced the colorectal distention(CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2(C-C motif chemokine ligand 2) in colon-related DRGs at the m RNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantlyaltered in NCI rats. CCL2 was co-expressed in Neu Npositive DRG neurons but not in glutamine synthetasepositive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding-and calcitonin generelated peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in mi R-325-5 p-positive DRG neurons. Intrathecal injection of mi RNA-325-5 p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose-and time-dependent manner. These data suggest that NCI suppresses mi RNA-325-5 p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus

Meniscus is a wedge-shaped fibrocartilaginous tissue,playing important roles in maintaining joint stability and function.Meniscus injuries are difficult to heal and frequently progress into structural breakdown,which then leads to osteoarthritis.Regeneration of heterogeneous tissue engineering meniscus(TEM)continues to be a scientific and translational challenge.The morphology,tissue architecture,mechanical strength,and functional applications of the cultivated TEMs have not been able to meet clinical needs,which may due to the negligent attention on the importance of microenvironment in vitro and in vivo.Herein,we combined the 3D(three-dimensional)-printed gradient porous scaffolds,spatiotemporal partition release of growth factors,and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures,excellent biomechanical properties and anti-inflammatory and anti-oxidant effects.By observing the results of cell activity and differentiation,and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro,we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation,with a view to cultivating a high-quality of TEM from bench to bedside.