Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.

The long-term extensive economic development has caused China's resource and environmental problems, especially the resource misallocation. The way China prioritises its limited resources is being significantly impacted by the rise of the digital economy and the interconnectedness of new technologies and the real economy. This paper quantitatively examines the linear and nonlinear impacts and mechanisms of digital development represented by internet development. With a series of empirical tests, we found that the internet development has significantly inhibited the resources misallocation, and the conclusion is still valid in the robustness test with internet popularization and internet infrastructure as the core explanatory variables. In addition to the marketization, internet development can further inhibit resource misallocation by promoting financial development, openness, urbanization and industrial structure. The findings of threshold regression suggest that the inhibitory effect of internet growth on resource misallocation becomes more visible as the degree of financial development and industrial structure increases; with the higher degree of urbanisation and marketization, although the internet development has always played an inhibitory role on resource mismatch, the inhibitory effect first increases and then decreases; with the improvement of openness, the hindering impact of internet growth on resource mismatch becomes more visible as the degree of financial development and industrial structure increases.

Trust beneficiary protection constitutes an important legal system in the trust industry. This paper, based upon the study approach of the “Theory of Law and Finance”, establishes the trust beneficiary protection index of China. We also test the influence of trust beneficiary protection on the performance of trust companies. As indicated by our study’s results, an “inverted U-shaped” relationship exists between the degree of trust beneficiary protection and the performance of trust companies. In a period when the trust law system has not yet been well established, strengthening trust beneficiary protection could help facilitate the growth of trust company performance. However, this facilitation effect gradually diminishes as the trust law system becomes more perfect. This in turn means that, after reaching a certain peak, conferring the beneficiary with more rights of supervision and participation would cause the performance of trust companies to decline. Improving regional legal environments could also help facilitate the growth of trust company performance. In addition, this facilitation effect is subject to the influence of the nature of trust company controllers. In trust companies controlled by local state-owned capitals, we find that the facilitation effect of the improvement of regional legal environments on trust company performance is inhibited. In trust companies controlled by non-state-owned capitals, however, the facilitation effect of the improvement of regional legal environments on trust company performance is enhanced.

Many of Keynes´s ideas and concepts are proven correct in this paper. The demand side, mainly business investments, drives the economy. Business firms steer the business cycle via profit expectations and animal spirits. Injections to and withdrawals from the circular flow of income are multiplied throughout the economy in accordance with Keynes´s multiplier. A sudden and sharp rise in households´ saving rates has a detrimental effect on aggregate demand, in line with Keynes´s paradox of thrift. Finance, not saving in the S=I sense, is the necessary condition for business investments and economic growth to be realized. Keynes´s finance motive thus makes money endogenous, contradicting the textbook result that exogenous money steers aggregate demand, contradicting the mainstream loanable funds theory and putting into question the Keynesian theory of sticky prices as a condition for real growth. However, a crucial omission in Keynes´s productive writings is the lack of an accelerator tying income to investment. Some of his followers such as Paul Samuelson tried to remedy that by developing multiplier-accelerator models. The problem with them is that the accelerator lacks micro foundations, in specific disregarding business confidence. Linking macro accounting identities with empirical national accounts data for five major economies produces the finding that business firms explain more than all aggregate expenditure growth during a 25-year period. Thus, it is concluded that business confidence is the root of the business cycle. Making the accelerator account for business confidence casts new light on the perhaps most well-known Keynesian “truth”: active fiscal policy as a main force stabilizing the business cycle. With business confidence being the endogenous and ubiquitous variable driving the business cycle, it turns out that any exogenous factor has the possibility to affect it. Policy needs to be viewed as a competing factor to the factor(s) driving the cycle in the other, destabilizing direction. The more powerful those factors are (e.g., a deadly virus), the tougher it gets for policy to “win” the competition, turning business confidence around. This leads up to the paper´s main conclusion: the worse the economy, the stronger is the case for active fiscal policy, but the lesser is the chance for it to succeed.

Since the Industrial Revolution, the emission of carbon dioxide and other greenhouse gases by human production activities has increased year by year, and the greenhouse effect has also increased. A series of problems, such as global warming, melting of the Antarctic continent, sea level rise and frequent occurrence of extreme climate, have attracted the attention of countries all over the world. As a developing country with the fastest economic growth rate, China's rapid economic growth is inseparable from the contribution of manufacturing industry. As an important engine of China's economic development, manufacturing industry inevitably brings environmental problems and a large number of greenhouse gas emissions while promoting rapid economic development. Therefore, manufacturing has become a major area for China to achieve its carbon emission reduction targets. With the "Made in China" to the world, the export trade of manufacturing industry plays a decisive role in China's total export trade and even the global trade. But whether the huge export demands will affect carbon emissions. Through the empirical study on carbon emissions of China's manufacturing export trade, the paper found that the increase of export demand of manufacturing industry will indeed bring a significant increase in carbon emissions, but also affected by some other factors. Finally, it provides reference for the high-quality development and export of China's manufacturing industry under the background of the target of “dual-carbon”.

The latent transforming growth factor-beta (TGF-β) binding protein 1 (LTBP1) has been implicated in various cellular processes, but its role in triple-negative breast cancer (TNBC) remains unclear. In this study, we investigated the impact of LTBP1 on TNBC progression and its underlying mechanisms. Analysis of online datasets revealed elevated LTBP1 mRNA expression in breast cancer tissues compared to normal adjacent tissues. Kaplan-Meier Plotter analysis indicated that high LTBP1 expression was negatively correlated with relapse-free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS) of breast cancer patients. Additionally, LTBP1 mRNA levels were associated with chemotherapy resistance. Functional assays in TNBC cells demonstrated that LTBP1 knockdown suppressed cell proliferation, induced apoptosis, and attenuated migration and invasion. In vivo studies confirmed that LTBP1 knockdown inhibited tumor growth in a xenograft mouse model. Mechanistically, LTBP1 positively correlated with genes involved in signaling regulation and organelle organization, with significant associations to GTPase binding and the RhoA/ROCK pathway. LTBP1 knockdown reduced RhoA activity and phosphorylation of Myosin Light Chain 2 (MLC2), suggesting inhibition of the RhoA/ROCK signaling pathway. Moreover, activation of the RhoA/ROCK pathway partially rescued the effects of LTBP1 knockdown on TNBC cell proliferation, apoptosis, migration, and invasion. In conclusion, our findings suggest that LTBP1 promotes TNBC progression through activation of the RhoA/ROCK signaling pathway, highlighting its potential as a therapeutic target for TNBC.

This research delves into the temporal dynamics of a nation's pursuit of a targeted GDP per capita level, employing five different survival machine learning models, remarkably Deep Learning algorithm (DeepSurv) and Survival Random Forest. This nuanced perspective moves beyond static evaluations, providing a comprehensive understanding of the developmental processes shaping economic trajectories over time. The economic implications underscore the intricate balance required between calculated risk-taking and strategic vulnerability mitigation. These findings guide policymakers in formulating resilient economic strategies for sustained development and growth amid the complexities inherent in contemporary economic landscapes.

Macrophages are a type of white blood cells that can exist in two different functional states, known as M1 and M2. M1 macrophages secrete pro-inflammatory cytokines that can promote tumor growth and metastasis, whereas M2 macrophages secrete anti-inflammatory cytokines that can inhibit tumor progression. This phenomenon, referred to as macrophage polarization, has been implicated in the development and progression of cancer. Furthermore, macrophage polarization is currently being investigated in the context of COVID-19 severity. It is believed that M1 macrophages may contribute to the excessive inflammation observed in severe COVID-19 cases, while M2 macrophages may confer protection against the disease. Hence, comprehending the role of macrophage polarization in both cancer and COVID-19 has the potential to enhance treatment strategies for both conditions.

This paper examines the link between informality and corruption, two interlinked phenomena that have negative impacts on economic development. The paper presents a neoclassical model simulation that illustrates how informality can drive corruption in the economy, emphasizing the incentives for corruption in an economy with informal and formal sectors. The model provides insights into the mechanisms that promote corruption and how policymakers can reduce it through formalisation. The paper reviews the existing literature on informality and corruption, highlighting the empirical evidence and theoretical models that support the relationship between the two. The research finds that countries with larger informal sectors tend to have higher levels of corruption. The study contributes to the ongoing debate on how to reduce corruption and promote formalisation, which are crucial for sustainable economic growth.

We analyze the annual microdata of China's 100 commercial banks from 2007 to 2018 using the mediating effect analysis method, analyze the negative impact of economic policy uncertainty on the credit scale of commercial banks, and then verify the intermediary effects of the operational risks and short-term capital liquidity of commercial banks in the impact of economic policy uncertainty on the scale of commercial bank credit, separately. Moreover, we find that non-state-owned commercial banks, large-scale commercial banks, low-leverage commercial banks, and commercial banks with low profitability are more susceptible to economic policy uncertainty affecting commercial bank credit growth through short-term capital liquidity, and vice versa.

Skateparks, often called 'wheel parks,' are becoming increasingly common within communities worldwide. Despite this growth in parks, estimates show that the development of parks needs to catch up to users. Using a count data travel cost model, we estimate the adult user benefits associated with the Lauridsen Skatepark in Des Moines, Iowa – the largest in the United States. We estimate adult user benefits to be $61 per user per day and roughly $488,000 annually. This work contributes to the literature by being the first study to use econometric techniques to estimate skatepark user benefits. Second, we develop a simple and easy-to-apply method to assist municipalities in determining community skatepark needs. Third, our results support the literature showing that skateboarders are increasingly diverse.

We study analytically the conflict of goals between stabilizing economic activity and public debt sustainability, for the fiscal authorities. In the short run, an active and expansionary fiscal policy, increasing public investment or reducing the labor taxation rate, is growth enhancing. However, as these short term fiscal policies also decrease government revenue and increase the public debt, budgetary and fiscal multipliers are reduced in the long run. In the framework of a potential ZLB constraint for monetary policy, an expansionary fiscal policy is thus appropriate only if long term labor and consumption taxation rates are small, and if the share of public expenditure in GDP is high. On the contrary, fiscal policy should be contractionary, in order to insure the sustainability of the long term public debt, if long term labor and consumption taxation rates are high. A contractionary fiscal policy is then also all the more appropriate as the sensitivity of government expenditure to the public debt is high, and as the labor share in the production function is high.

This study investigates the likelihood of time to bank failures in the US between 2001 and April 2023, based on data collected from the Federal Deposit Insurance Corporation's report on "Bank Failures in Brief - Summary 2001 through 2023". The dataset includes 564 instances of bank failures and several variables that may be related to the likelihood of such events, such as asset amount, deposit amount, ADR, deposit level, asset level, inflation rate, short-term interest rates, bank reserves, and GDP growth rate. We explore the efficacy of machine learning survival models in predicting bank failures and compare the performance of different models. Our findings shed light on the factors that may influence the probability of bank failures with a time perspective and provide insights for improving risk management practices in the banking industry.

The very nature of work, labor market composition, and skill requirements are severely affected by technology-driven transformations currently underway with the 4^th industrial revolution (4IR). The effect of 4IR technologies on technical and vocational education and training (TVET) and the contribution of TVET to the labor market is explicit. The paper presents the findings of a study that investigated whether TVET institutions are prepared to face the challenges of 4IR. The data for the study were collected by surveying 428 teachers from 15 countries in Asia and the Pacific engaged in science, technology, engineering, and mathematics (STEM) fields at the tertiary level. The findings of our study undoubtedly bring greater attention to the initiatives of TVET in these countries in preparing the workforce for job roles necessitated in the 4IR. The findings can also be used to frame policy recommendations for the growth of economies.

You have a product or service for which the world has been waiting. You've scraped together enough cash to get your idea off the ground. You are confident that your business will succeed. And yet, it is often the case that a short time later you are out of business. Numbers from the U.S. Bureau of Labor Statistics indicate that about half of new businesses fail within the first five years. And with those business failures go the life savings and the dreams of the person who started the business. This article describes five finance and accounting pitfalls that should be avoided in order to increase the likelihood that a small business will succeed. Of course, the most common reason for a small business to fail is that customers don't want the product or service. But small businesses are also often killed because of predictable and preventable finance and accounting mistakes: insufficient capital, poor cash management, poor record keeping and controls, improper product pricing, and uncontrolled growth.

The development of digital economy is becoming an important path to promote the kinetic energy of China's tax revenue development. Based on the panel data from 2011 to 2018, this paper uses Gini coefficient to analyze the regional differences of China's digital economy, and uses fixed effect model, spatial Durbin model, multi-period double difference model and other empirical methods to examine the tax effects of digital economy development. The results show that the regional disparity is the main reason for the regional disparity of digital economy development in China. The development of digital economy directly increases the tax amount of local digital industry, and at the same time it also radiates and drives the increase of local total tax revenue; The tax effect of digital economy has a negative spatial spillover, showing a "siphon effect" to neighboring areas; Mechanism analysis shows that the development of digital economy mainly promotes the increase of local tax revenue through growth effect.

Renewable energy has become a crucial topic in recent years as the world is moving towards environment friendly and sustainable energy sources. The aim of this research paper is to analyze the effectiveness and efficiency of renewable energy resources such as geothermal, hydro, solar and wind energy in comparison to typical and traditional energy resources such as oil and coal. This paper focuses on the current state of renewable energy adoption, the benefits and drawbacks of all types of renewable energy resources, and the challenges faced in implementing renewable energy on a large scale. Through a comprehensive literature review, this paper discusses the methodologies and results of various studies conducted to understand the potential of renewable energy sources by secondary means. This research paper also presents an original analysis of renewable energy data to identify the most efficient and cost-effective renewable energy source. The results of this study indicate that renewable energy sources can be an effective and efficient replacement for traditional energy sources, but they face significant challenges in adoption and implementation. The study concludes with recommendations for future research and policy changes that can support the growth of renewable energy sources.

The digital economy based on digital technology is an important force for high-quality economic growth and industrial transformation, and has great potential for value creation. Based on the data of 30 provinces in China from 2007 to 2017, this paper uses entropy method to calculate the industrial green transformation (IGT), and empirically analyzes the impact of Digital economy on IGT. The DE can significantly reduce IGT of local and neighboring areas after excluding the influence of macro system factors and replacing the spatial weight matrix. The DE can indirectly reduce the IGT by accelerating the accumulation of human capital, and green technology innovation. The impact of digital economy on IGT is a non-linear relationship. With the further improvement of environmental regulation, financial development and intellectual property protection, the role of digital economy in IGT is more obvious. To this end, it is necessary to speed up the construction and improvement of digital infrastructure, build an integrated layout of "digital infrastructure", give full play to the radiating role of the digital economy, and implement differentiated development paths based on regional comparative advantages.

At present, global warming poses the greatest threat to the planet's ecosystem. China is the greatest CO2 emitter, expected to account for roughly 33% of overall emissions in 2021, and this has caused authorities to express significant concern in the most latest Paris accord, when they decided to cut global emissions to a particular level. In comparison, 55% of China's power in 2021 appears from coal. As a result, investigating the ecological elements that affect China's CO2 output is essential. This analysis utilizes the autoregressive distributed lag (ARDL) technique to investigate the relationships concerning fossil fuels, renewables, and economic growth from 1990 to 2021. According to the data, using fossil fuels to generate energy and increase GDP significantly increases CO2 emissions. Yet, the use of renewable energy reduces CO2 emissions both in the long run and in the short term. Overall, the outcomes imply that using renewable energy sources is key to reaching sustainable environmental goals and deters the usage of fossil fuels in the energy mix. This study suggests that China take into account empirical findings and undertake long-term initiatives to reduce carbon emissions in favor of sustainable environmental outcomes.

The paper is motivated by the growth of the electronic payments system and its relevance in enhancing the banking industry's earnings. Consequently, the paper examines the causal relationship between the electronic payments system and the banking industry's returns in Nigeria. The paper offers some important contributions to the literature involving the use of an approach that allows for data-driven identification of the change points in the electronic payments system and the banking industry's returns nexus. The paper discovered three important findings. First, the causal relationship between the electronic payments system and the banking industry's returns in Nigeria changes with time changes. Second, there is evidence of causality between the electronic payments system and returns on assets and equity, however, the causality was more evident under the recursive window. Third, the causal relationship was more evident in some specific periods such as 2020Q4, all quarters of 2015 to 2016, and 2020 to the end of 2023. The paper recommends that policymakers should revisit and reinvigorate the specific cashless policies instituted in 2012-2016 that aided higher returns to the banking industry. Similarly, the Central Bank of Nigeria and other banking industry players should intensify efforts to encourage the use of electronic payments due to their usefulness and ability to enhance the banking industry's earnings.