沉默MPZL1调控β-catenin对A549/Tax细胞干性及耐药性的影响

目的探讨髓磷脂蛋白零样蛋白1(MPZL1)沉默后是否通过调控β-catenin表达对A549/Tax耐药性和细胞干性产生影响。方法采用不同浓度阿霉素和紫杉醇处理A549和A549紫杉醇耐药性(A549/Tax)细胞,观察两种细胞的耐药性差异。实时荧光定量聚合酶链式反应(qRT-PCR)和Western blot检测A549和A549/Tax细胞中MPZL1的表达量差异。对A549/Tax细胞沉默或者过表达MPZL1,进一步将细胞分为对照(control)组、短发卡RNA阴性对照(sh-NC)组、MPZL1沉默(sh-MPZL1)组、过表达阴性对照(OE-NC)组、MPZL1过表达(OE-MPZL1)组,运用细胞计数试剂盒8(CCK-8)和平板克隆实验分别检测MPZL1的表达变化对A549/Tax细胞增殖和克隆形成能力的影响。Western blot检测Wnt/β-catenin抑制剂XAV939和激活剂CHIR-99201处理细胞后,不同蛋白的表达变化。结果A549/Tax细胞对阿霉素和紫杉醇的半数抑制浓度(IC 50)较A549细胞明显增加(P<0.01)。MPZL1在A549/Tax中呈更高的表达趋势。MPZL1敲除后A549/Tax对阿霉素和紫杉醇的IC 50分别为2.731 mg/ml和4.939μg/ml,较阴性对照组的4.541 mg/ml和13.55μg/ml降低(P<0.01)。CCK-8和克隆形成实验结果显示,MPZL1敲除抑制肺癌A549/Tax细胞的增殖活力和克隆形成能力(P<0.05);Western blot结果显示,与阴性对照组相比,MPZL1、肿瘤干性相关蛋白(CD44和CD133)、多药耐药蛋白1(MDR1)、肺耐药相关蛋白(LRP)和β-catenin在sh-MPZL1中的表达水平明显减少(P<0.01)。此外,XAV939可抑制MPZL1、CD44、CD133、MDR1、LRP和β-catenin的表达。CHIR-99201处理细胞后部分逆转敲除MPZL1对上述蛋白的抑制作用。结论MPZL1在肺癌A549/Tax细胞中高表达。敲除MPZL1可抑制肿瘤干性和细胞增殖,增强肺癌A549/Tax细胞对阿霉素和紫杉醇的敏感性。

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental effects.This highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained elusive.Here,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in NSCs.Conditional deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse phenotype.Notably,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation.Conversely,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration.Furthermore,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO mice.Collectively,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

Effect of Property Tax on Optimization and Upgrading of Industrial Structure

China's economic growth and economic development has entered a new stage,and the optimization and upgrading of industrial structure is the core driving force for China to achieve high-quality economic development during the"14 th Five-Year Plan"period.Property tax has a conductive effect on the upgrading of industrial structure.Therefore,from the perspective of property tax and industrial structure adjustment and the relationship between them,this study summarizes the relevant research of domestic and foreign scholars.On the basis of the research,the paper puts forward some relevant policy suggestions on improving China's property tax and promoting the optimization and upgrading of China's industrial structure.

Exploring Corporate Tax Compliance in the Era of Digital Tax Collection and Administration:Insights from the“Golden Tax Phase Four”Project

This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementation of the“Golden Tax Phase Four.”With this backdrop,the article offers recommendations for advancing the reform of the tax collection and management system,fostering the development of intelligent taxation,and accelerating the modernization of tax collection and management in China.

Research on Tax Risk Regulation and Strategic Management in the Context of Big Data

With the rapid development of big data,big data has been more and more applied in all walks of life.Under the big data environment,massive big data provides convenience for regional tax risk control and strategic decision-making but also increases the difficulty of data supervision and management.By analyzing the status quo of big data and tax risk management,this paper finds many problems and puts forward effective countermeasures for tax risk supervision and strategic management by using big data.

Taxation Models and Improvement Proposals for Personal Income Tax in the Sharing Economy

As an innovative economic model,the sharing economy has seen rapid growth globally in recent years.It has not only brought a profound impact on traditional economies but also injected new vitality and momentum into the sustainable development of the social economy.However,for the sharing economy,the process of collecting personal income tax is facing several issues,such as the ambiguity of tax policies regarding personal income,challenges in identifying taxpayers,and difficulties in defining income.To achieve the fairness and efficiency of personal income tax collection in the sharing economy,this study proposes optimized regulatory mechanisms and conducts in-depth discussions on the adjustment of personal income tax policies,innovation in tax management technology,and improvement in the quality of personal income tax services.

Analysis and Innovative Strategies of Tax Preferential Policies to Promote the Sustainable Development of Small-Scale Individual Businesses

This study conducted an in-depth analysis of the current tax preferential policies for small-scale individual businesses and compared them with similar policies both domestically and internationally,aiming to reveal the advantages and disadvantages of the current system.After examining the impact of these tax preferential policies on the economic status of individual business owners and the broader social economy,this article proposes a set of innovative tax preferential strategies based on theoretical foundations.By developing these innovative strategies and clarifying their implementation paths,the aim is to promote the sustainable and healthy development of small-scale individual businesses,thereby fostering comprehensive socio-economic progress.The conclusion of this study not only summarizes policy recommendations with practical significance but also provides theoretical support for the optimization and innovation of future related systems.

Non-Value-Added Tax to improve market fairness and quality

The promotion of both market fairness and efficiency has long been a goal of securities market regulators worldwide.Accelerated digital disruption and abusive trading behaviors,such as the GameStop mania,prompt regulatory changes.It is unclear how this“democratization”of trading power affects market fairness as economies cope with pandemic-driven shifts in basic systems.Excessive speculation and market manipulation undermine the quality of financial markets in the sense that they cause volatil-ity and increase the pain of bubble and crash events.Thereby,they weaken public confidence in financial markets to fulfill their roles in proper capital allocation to irrigate the real economy and generate value for society.While previous studies have mostly focused on market efficiency,our study proposes a tool to improve market fairness,even under periods of stress.To encourage value generation and improve market quality,we advance a graduated Non-Value-Added Tax that we implement in an agent-based model that can realistically capture the properties of real-world financial markets.A profitable transaction is taxed at a higher rate if it does not enhance the efficiency measured by deviation from fundamentals.When an agent locks in profit not supported by fundamentals but driven by trend-following strategies,the generated profit is taxed at various rates under the Non-Value-Added Tax regime.Unlike existing financial transaction taxes,the non-value-added tax is levied on profit rather than on price or volume.We show that the proposed tax encourages profitable trades that add value to the market and discourages valueless profit-making.It significantly curtails volatility and prevents the occurrence of extreme market events,such as bubbles and crashes.

Brief analysis on value-added tax transformation and its influence on enterprises

From Jan. 1st, 2009, the value-added tax transformation will be performed in all industries around the country. Based on value-added tax types and retrospection of reform practices, this article analyzes the background of the national value-added tax transformation and points out the influence of full implementation of the value-added tax transformation on various enterprises.

Value-Added Tax （VAT） on Selected Financial Transactions

This paper deals with the approach to imposing value-added tax （VAT） on financial transactions. The VAT is a highly harmonized consumption tax within the European Union （EU）. VAT operational rules have been set down by the relevant directive of the Council of the EU. Under the directive, it is possible to select either exemption or taxation of financial transactions. Only the first option is permitted in the Czech Republic. Pros and cons of both models are described, in particular, the problems with determining the difference between financial transactions and other similar performance that must always be subject to tax. Potential lower VAT revenue or tax base assessment, as appropriate, seems to be crucial in the case of the taxation of financial transactions.

The Empirical Analysis on Cognitive Degree of the Restaurant Industry to ＂Replace the Business Tax with Value-added Tax＂

The restaurant is traditional industry of the third industry in our country. Since May 1 in this year, China＇s Restaurant Industry to implement ＂replace the business tax with value-added tax＂ policy and change to pay VAT. This paper analyzed the possible impact on restaurant industry after the＂ replace the business tax with value-added tax＂ based on the understanding of the tax theory of＂ replace the business tax with value-added tax＂ and the tax compliance in our country. At the same time, this paper used the statistical analysis of data on the investigation of 100 samples of the VAT cognitive degree on ＂replace the business tax with value-added tax＂, using principal component analysis method to analyze and evaluate factors on the awareness of the restaurant owner to ＂replace the business tax with value-added tax＂ tax policy. After multiple comparison made on the sample data, this paper summarized and analyzed the countermeasures of improving the pushing effect in restaurant industry ＂replace the business tax with VAT ＂.

Impact of taxes on the 2030 Agenda for Sustainable Development:Evidence from Organization for Economic Cooperation and Development(OECD)countries

Multiple ecological and socioeconomic problems have occurred worldwide,raising the awareness of sustainability.This study aims to examine the impact of taxes on Sustainable Development Goals(SDGs)in the context of Organization for Economic Co-operation and Development(OECD)countries.This research used effective average tax(EAT),tax on personal income(TPI),tax on corporate profits(TCP),and tax on goods and services(TGS)as the variables of taxes,and employed secondary data from 38 OECD countries covering 2000–2021.The study also used Breusch-Pagan Lagrange Multiplier(LM),Pesaran Scaled LM,Bias-Corrected Scaled LM,and Pesaran Cross-sectional dependence(CSD)tests to analyze the existence of crosssectional dependency.Then,we established the stationarity of variables through second-generation panel unit root tests(Cross-sectional Augmented Dickey-Fuller(CADF)and Cross-sectional Im,Pesaran,and Shin(CIPS)),and confirmed the long-run cointegration of the variables by using secondgeneration panel cointegration test(Westerlund cointegration test).The results showed that EAT,TPI,TCP,and TGS are positively associated with SDGs.However,the change in TPI has a smaller effect on SDGs than the change in EAT or TCP or TGS.The result of panel causality indicated that EAT,TPI,and TGS have a unidirectional causal relationship with SDGs.The study also found that TCP has a bi-directional causal relationship with SDGs.Moreover,the finding indicated that the OECD countries need to focus on tax policies to achieve the 2030 Agenda for Sustainable Development.This study is based on the theory of optimal taxation(TOT),which suggests that tax systems should be designed to maximize social welfare.Finally,we suggests the importance of taking a comprehensive approach for the managers and policy-makers when analyzing the impact of taxes on SDGs.

Dynamic decision and its complex dynamics analysis of low-carbon supply chain considering risk-aversion under carbon tax policy

This study establishes a low-carbon supply chain game model under the centralized decision situation and the decentralized decision situation considering the manufacturer risk-aversion behavior, and discusses the influence of the manufacturer risk-aversion behavior on the optimal decision, profit, coordination, and complex dynamics of the supply chain. We find that comparing with the risk-neutral decentralized decision, the increase of manufacturer's risk tolerance attitude can narrow the gap between the supply chain profit and the centralized decision, but it will further reduce the carbon emission reduction level. The increase of risk tolerance of the manufacturer and carbon tax will narrow the stable region of the system. Under this situation, the manufacturer should carefully adjust parameters to prevent the system from losing stability,especially the adjustment parameters for carbon emission reduction level. When the system is in a chaotic state, the increase of carbon tax rate makes the system show more complex dynamic characteristics. Under the chaotic state, it is difficult for the manufacturer to make correct price decision and carbon emission reduction strategy for the next period, which damages its profit, but increases the profit of the retailer and the supply chain. Finally, the carbon emission reduction cost-sharing contract is proposed to improve the carbon emission reduction level and the supply chain efficiency, achieving Pareto improvement. The stability region of the system is larger than that in the centralized decision situation, but the increase of the cost sharing coefficient will reduce the stability of the system in the decentralized decision-making situation.

A Multi-Module Machine Learning Approach to Detect Tax Fraud

Tax fraud is one of the substantial issues affecting governments around the world.It is defined as the intentional alteration of information provided on a tax return to reduce someone’s tax liability.This is done by either reducing sales or increasing purchases.According to recent studies,governments lose over$500 billion annually due to tax fraud.A loss of this magnitude motivates tax authorities worldwide to implement efficient fraud detection strategies.Most of the work done in tax fraud using machine learning is centered on supervised models.A significant drawback of this approach is that it requires tax returns that have been previously audited,which constitutes a small percentage of the data.Other strategies focus on using unsupervised models that utilize the whole data when they search for patterns,though ignore whether the tax returns are fraudulent or not.Therefore,unsupervised models are limited in their usefulness if they are used independently to detect tax fraud.The work done in this paper focuses on addressing such limitations by proposing a fraud detection framework that utilizes supervised and unsupervised models to exploit the entire set of tax returns.The framework consists of four modules:A supervised module,which utilizes a tree-based model to extract knowledge from the data;an unsupervised module,which calculates anomaly scores;a behavioral module,which assigns a compliance score for each taxpayer;and a prediction module,which utilizes the output of the previous modules to output a probability of fraud for each tax return.We demonstrate the effectiveness of our framework by testing it on existent tax returns provided by the Saudi tax authority.

Tax avoidance and earnings management:a neural network approach for the largest European economies

In this study,we investigate the relationship between tax avoidance and earnings management in the largest five European Union economies by using artificial neural network regressions.This methodology allows us to deal with nonlinearities detected in the data,which is the principal contribution to the previous literature.We ana-lyzed Compustat data for Germany,the United Kingdom,France,Italy,and Spain for the 2006–2015 period,focusing on discretionary accruals.We considered three tax avoidance measures,two based on the effective tax rate(ETR)and one on book-tax differences(BTD).Our results indicate the presence of nonlinear patterns and a posi-tive,statistically significant relationship between discretionary accruals and both ETR indicators implying that when companies resort to earnings management,a larger tax-able income—and thus higher ETR and lesser tax avoidance–would ensue.Hence,as also highlighted by the fact that discretionary accruals do not appear to affect BTD,our evidence does not suggest that companies are exploiting tax manipulation to reduce their tax payments;thus,the gap between accounting and taxation seems largely unaf-fected by earnings management.

Fairness in Climate Change Mitigation: The Case of Carbon Taxation

Environmental economists have advocated carbon taxation for its efficiency and effectiveness in reducing Greenhouse Gas (GHG) emissions. Yet, whether the policy would be fair in any given context needs to be better realized. While the distributive effects of carbon taxation have been widely discussed, a more comprehensive understanding of tax fairness is lacking. This paper reviews the academic literature through the lens of three justice concepts -recognition, procedure, and distribution—to understand the implications of previous studies for fair carbon tax policy-making. Upon examining the relevant literature, the findings highlight the limited evidence concerning recognition and procedural justice in carbon taxation, particularly in developing country context. This calls for more assessments through these perspectives. It also emphasizes the importance of recognition for vulnerable groups, such as women, with an intersectionality approach;a fair policy process through information provision, inclusive representation, fair level playing field;and proportionate burden sharing through context-specific design elements such as targeted revenue use.

Does higher tax rate affect tobacco usage?Unravelling the nexus between tobacco regulatory control and public health concern

Objectives:Bangladesh stands as a prominent global consumer of tobacco,with alarming consequences on public health.The Global Adult Tobacco Survey reported that tobacco consumption claimed over 126000 lives in 2018,contributing to 13.5%of all deaths in the country.This study aims to explore the effectiveness of higher tax rates and tobacco use regulation as control mechanisms in mitigating tobacco consumption and health care cost burden,with a particular emphasis on its implications for public health.Methods:This study is based on the annual time series data over the period 2000-2020.The study employs the ordinary least square method to analyze the quantitative confirming the stationarity of data at level.This research uses different models to investigate individual effects and combined effects on both tobacco consumption and tobacco health care cost burden.Results:The study finds a negative relationship between tobacco tax rate and tobacco consumption.More specifically,the higher tax rate of tobacco(low(β=-0.3495),medium(β=-0.2319),high(β=-0.9033),premium(β=-0.7322),filtered(β=-0.2114),and non-filtered(β=-0.3452)categories)is significant to reduce tobacco use at 1%level of significance.The study finds similar results when it applied tobacco retail price instead of tobacco tax rate as the independent variable.Finally,the study investigates the impact on health care cost through tobacco consumption,tobacco control law,growth rate,export-import,and tobacco production.The results indicate that tobacco consumption,export-import,and tobacco production increases health care cost burden while tobacco use regulatory decreases it.By reducing tobacco consumption,higher taxes and tobacco use regulation contribute to alleviating the burden on the healthcare system,promoting healthier lifestyles,and aligning with global health objectives.Conclusions:Higher tax rate on tobacco products is necessary to increase the retail price so that tobacco users cannot consume tobacco.Specific tax and uniform tax base are needed so that tobacco users cannot switch to lower priced brands.Tobacco control laws need to revised and proper implementation should be ensured as well,to achieve the goal of tobacco free Bangladesh by 2040.Tobacco-related diseases,responsible for a significant proportion of deaths in the country,could witness a considerable decline with the successful implementation of higher tax rates and tobacco use regulation.This study provides insights that not only contribute to the economic discourse but also accentuate the broader public health benefits arising from effective tobacco taxation policies.

The Effect of Foreign Direct Investment on Air Pollution in the Economic Community of West African States region: What Influence Does Tax Expenditure Have?

Air pollution is one of the crucial environmental challenges facing the countries of the Economic Community of West African States (ECOWAS). The objective of this paper is to examine the effect of an attractive tax policy on the relationship between Foreign Direct Investment (FDI) and air pollution in ECOWAS region over the period 2000 to 2019. By using the Ordinary Least Squares (OLS) method and panel data analyses (fixed effects and random effects), the results show that, in general, FDI does not have a significant effect on air pollution in the region. However, closer analysis reveals that an interaction between FDI and an attractive tax policy has a negative effect on air quality, leading to an increase in air pollution. Thus, companies attracted by tax incentives may not meet rigorous environmental standards. These results highlight the importance for policymakers to balance economic incentives with environmental protection in ECOWAS. Attractive tax policies can stimulate investment, but they must be designed in a way that encourages environmentally friendly practices, thereby helping to improve air quality in the region.

Analysis on the Influence of "Replacement of Business Tax by Value-added Tax" on the Cost of Highway Projects

The"replacement of business tax by VAT reform"(hereby refer to as"VAT reform"for short)is a newly promulgated and implemented tax policy,and its impact on various industries in China is very different,and the highway project industry is no exception.The implementation of the"VAT reform"will not only have a positive impact on the cost of highway projects,but will also have some negative impacts.For this reason,highway project construction corporates must actively respond.The author explores and analyzes the positive and negative effects of the"VAT reform"on the cost of highway projects,and proposes a reform strategy for highway project cost work under the background of the"VAT reform",in hope of helping with bringing out the intrinsic value of highway project cost management work.

Overview of the Reports on the Reformation of Personal Income Taxation

Presentation of the reports on the reformation of personal income taxation that have been prepared with a development plan for the Greek economy,that discuss the issue of taxation and point out its important features.The goal is the complete modernization of the tax system,so that it responds more fully to the principles of social justice,contributes to the economic development of the country and is governed by simple and modern procedures,which apply to all tax objects.The purpose of the study is to deepen the proposals for tax reform based on the peculiarities of the Greek economy,the international trends in this field and the weaknesses of the tax system.The effects of a tax reformation are analyzed and how it should take the form of the reform,which,however,requires a new legislation,which will bring about radical and deep cuts,which respond to the new conditions and the internationalization of the economy.Proposals for a set of structural measures,which are necessary for the country’s adaptation to the wider European environment and the elimination of the weaknesses that increase its distance from the other member countries.Citation of the common points of the reports on the reformation of personal income taxation and their adoption by the tax leadership.