Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

Cervical cancer is defined as a cancer arising in the cells of cervix that causes unusual vaginal bleeding, discharges, pain in the pelvic region, or pain during sexual activity. Cervical cancer is currently reported to be the fourth most prevalent malignancy among women globally. Surgery includes pelvic lymphadenectomy as well as radical hysterectomy, radiotherapy, as well as chemotherapy are the most common therapies for treating cervical cancer. Another approach includes targeted medication which affects the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) for the curing cervical cancer. However, these therapies have the potential for risks and complications: surgery can result in bleeding and may cause organ damage surrounding the surgery, and clots may also start to form in the deep veins of the legs; radiotherapy can result in menopause, infertility, discomfort, or pain during intercourse; and chemotherapy can actually impact rapidly dividing cells along with cancer cells in the human body system. In this review, we will discuss about the use of several Randomised controlled trials (RCTs) for treating malnutrition in various oncology patients. In this review, we will discuss about the various therapeutic effects of natural products isolated from different microorganisms in treating cervical cancer.

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.

Global distributions of net factor income from abroad (NFI) during 1990-2019 have witnessed that (1) the United States is the top one country accounting for 40% of surpluses of the global total, while a surge in China’s deficit with its GDP increase; (2) GDP growth in emerging economies has a price scissors with NFI deficits; (3) asymmetric NFI has covered up the severity of rich countries’ global arbitrages especially from emerging economies; (4) China’s economic power is exaggerated by the PPP-based GDP implemented by the World Bank. It concludes that (1) developing countries have paid for huge hidden cost for their emergence; (2) the statement of the United States suffering losses absolutely does not hold; (3) GDP is not a universal tool for measuring what matters. It suggests that (1) emerging economies countries should beware of the potential misleading of GDP on economic measurement and economic power comparison ; (2) GDP should be critiqued from the applicability perspective of economies’ types; (3) it is urgent to clarify some misjudgment and misleading concepts in the economic affairs surrounding the global value chain patterns; (4) the construction of national governance capacity in emerging economies should focus on “social infrastructure”, of which one of the important parts is an effective economic statistics system; (5) emerging economies should carry out the strategic layout of international economic statistics talents to enhance their soft powers.

The impact of international tourism on emerging markets has been overwhelmingly beneficial. Despite the obvious benefits of tourism, it comes at a high price for the environment in the form of pollution. Brazil's annual tourist influx has the potential to boost economic development and damage the country's ecosystems. The objective of this investigation is to analyze, using time series data ranging from 1990 to 2019, the effects of tourism and economic growth (GDP) on carbon dioxide (CO₂) emissions in Brazil. The stationarity of the data was examined by employing unit root tests, and an autoregressive distributed lag (ARDL) technique was used to investigate the link between the factors, taking both the long- and the short-run into consideration. This research shows that there are long-term and short-term ties between Brazil's tourism industry, GDP, and CO₂ emissions. Yet, both tourism and economic expansion have had serious negative effects on Brazil's ecology. These results indicate that in order to maintain environmental quality in Brazil, policymakers need to pursue more eco-friendly economic expansion as well as environmentally conscious tourist regulations.

The objectives and tasks of the European Central Bank (ECB) are defined in Articles 2 and 3 of Protocol (No 4) on the Statute of the European System of Central Banks (ESCB) and of the European Central Bank (ECB). While in Article 3,1° of this Protocol other tasks are mentioned, the prime objective of the ESCB and therefore of the ECB, is price stability. This concept was originally specified by the Executive Board of the ECB as an annual increase of less than 2% in the inflation rate over the medium term, measured by the Harmonized Index of Consumer Prices (HICP) for the euro area. This paper examines to what extent the ECB has been effective in realizing price stability over the period from January 1, 2000 to December 31, 2022. Price stability is important for economic agents. It allows them to plan their savings, spending and investment eventually resulting in sustained economic growth.   Notwithstanding the commitment of large human and other resources and the use of unconventional monetary policies, the ECB did not realize its prime objective during a large part of this period. We conclude that putting too much confidence in DSGE-modeling as one of the methodologies to determine monetary policy, may have played an important role in the ECB not achieving its main statutory objective.

We employ the joint production decomposition model to conduct a full decomposition of CO2 emission among 36 industrial sectors in China from 1998 to 2011, under the framework of growth accounting. The results show that: (1) the average CO2 emission increases at an annual rate of 3.01%, and production technology progression is the main driving force, while the transformation toward clean production effectively curb the rapid growth of CO2 emissions; (2) the effect of technology changes on CO2 emission is larger during the "10th Five-Year Plan" compared with the "11th Five-Year Plan", which makes the annual growth rate of CO2 emission during the "11th Five-Year Plan" 1% lower than its counterpart; This study has important theoretical and practical significance for understanding the driving factors of CO2 emission and the corresponding emission reduction measures.

This paper describes two novel approaches to cost estimation of manufactured products where a data set of similar products have known manufactured costs. The methods use the notion of piecewise functions and are (1) clustering and (2) splines. Cost drivers are typically a mixture of categorical and numeric data which complicates cost estimation. Both clustering and splines approaches can accommodate this. Through four case studies, we compare our approaches with the often-used regression models. Our results show that clustering especially offers promise in improving the accuracy of cost estimation. While clustering and splines are slightly more complex to develop from both a user and a computational perspective, our approaches are packaged in an open-source software. This paper is the first known to adapt and apply these two well-known mathematical approaches to manufacturing cost estimation.

I will show that if the propensity to consume from savings satisfies appropriate conditions, the debt-GDP ratio will not grow infinitely large and fiscal collapse will not occur. Using a basic macroeconomic model, with an overlapping generations model in mind, we show the following results: 1) The budget deficit including interest payments on the government bonds equals an increase in the savings from a period to the next period. 2) If the savings in the first period is positive, we need budget deficit to maintain full employment under constant prices or inflation in the later periods. 3) Under an appropriate assumption about the propensity to consume from savings, the debt-GDP ratio converges to a finite value. It does not diverge to infinity. The larger the propensity to consume from savings, the smaller the budget deficit required to achieve full employment. The larger the propensity to consume from savings, the less likely it is that the debt-GDP ratio will become large.

Background: Bladder cancer (BLCA), particularly invasive BLCA, has become a medical burden worldwide as it is associated with recurrence and easy metastasis. There are specific differences in the expression of various miRNAs in tumor and normal tissues. Hence, miRNAs can be used as biomarkers for tumor diagnosis and prognostic evaluation. The current study aimed to predict the downstream target genes of BLCA-related miRNAs and explore their association with immune infiltration. Method: Data on BLCA-related mRNA and miRNA expression levels were downloaded from The Cancer Genome Atlas. Correlation analysis and Cox regression analysis were performed to validate the miRNA risk model. The infiltration of various immune cells should be compared to determine the distinct differences between the immunological microenvironment of the two risk groups. Results: A predictive framework of BLCA was established using the expression levels of two miRNAs. Cox regression analysis showed that the low-risk group had a better prognosis. Then, the target genes of miRNA were predicted, and the target genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Moreover, variations in immune cells and functions between the high- and low-risk groups were assessed. Conclusion: The prognostic features composed of two associated miRNAs (MIR-25, MIR-548AN) may help predict the overall survival of BLCA.

I examine the problem of budget deficit in a growing economy in which consumers hold money as a part of their savings in the case where consumers live forever. For simplicity and tractability I use a discrete time dynamic model and Lagrange multiplier method. In the appendix I briefly explain the solution using a discrete time version of the Hamiltonian method. I will show the following results. 1) Budget deficit is necessary for full employment under constant prices. 2) Inflation is induced if the actual budget deficit is greater than the value at which full employment is achieved under constant prices. 3) If the actual budget deficit is smaller than the value which is necessary and sufficient for full employment under constant prices, a recession occurs. Therefore, balanced budget cannot achieve full employment under constant prices. I do not assume that budget deficit must later be made up by budget surplus.

This research evaluates the efficacy of survival models in forecasting startup failures and investigates their economic implications. Several machine learning survival models, including Kernel SVM, DeepSurv, Survival Random Forest, and MTLR, are assessed using the concordance index (C-index) as a measure of prediction accuracy. The findings reveal that more sophisticated models, such as Multi-Task Logical Regression (MTLR) and Random Forest, outperform the standard Cox and Kaplan Meier (K-M) models in terms of predicted accuracy.

Triggered by the rising demand, a complex aircraft production network has been evolving during the past half century. In order to analysis the spatial-temporal evolution of this network, this paper establishes a novel and complex data by collecting 1774 major global aircraft manufacturers' production relationship from Jane's All the World' s Aircraft Development & Production (1965-2021), and visualizes the spatial temporal characteristics of the global aircraft production network by using Social Net Analysis method. The characteristics are summarized as follows: (1) the main aircraft firms from 48 counties form a complex production network centered on the United States, Europe and China; (2) The production network remains diffusion during 1965-2005, but it retracts after 2005, which documents evidences of de-globalization trend in the aircraft industry; (3)AVIC, Airbus, Boeing, Textron, Lockheed, Kawasaki, Mitsubishi, Sikorsky, Bell, and Embraer are all ranked high in the study period and play the role of leading firms in the production network and drive the cooperative connections of other companies.

The low-carbon city pilot is an important policy for promoting sustainable development and addressing climate change. The level of green technological innovation is a significant driving force for China's transition to high-quality development and the realization of carbon peaking and carbon neutrality goals. This essay takes the panel data of 30 provinces in China from 2008 to 2020 as the research sample, regards the number of urban green invention patent applications as a quantifiable indicator of the level of urban green technological innovation, and takes the policy of low-carbon city pilot as a quasi-natural experiment, and uses the difference-in-differences model to test the impact of low-carbon city pilot on the level of urban green technological innovation, and to investigate the mechanism of action within. The main conclusions are as follows: (1) The policy of low-carbon city pilot has an outstanding promotion effect on the level of urban technological innovation. (2) Using the mediating effect to analyze, it is found that the low-carbon city pilot policy can improve the level of urban green technological innovation through the development of green finance.

Green innovation, as a sustainable development approach, can synergistically promote high-quality economic and social development. We select China's A-share-listed manufacturing corporations from 2011 to 2021 as the research sample to empirically study the impact of executive academic experience on green innovation in manufacturing corporations. Further, we test the relationship between executive academic experience and green innovation in manufacturing corporations under the mediating role of corporate social responsibility and the moderating role of heterogeneous environmental regulations. The study shows that (1) executive academic experience helps to promote green innovation in manufacturing corporations; (2) executive academic experience is conducive to promoting the fulfillment of social responsibility by manufacturing corporations; (3) corporate social responsibility plays a mediating role between executive academic experience and green innovation in manufacturing corporations; (4) environmental regulation positively moderates the relationship between executive academic experience and green innovation in manufacturing corporations, and both formal environmental regulation and informal environmental regulation positively moderated the promotion of green innovation in manufacturing corporations by executive academic experience.

The primary goal of this research is to examine how different types of energy are used in South Asian countries and how they affect the environment and economic growth. From 1990 through 2021, this research employed Panel Data from multiple sources covering the South Asian countries of Pakistan, India, Bangladesh, Sri Lanka, Nepal, Bhutan, Maldives, and Afghanistan. The results are determined by using the Fixed Effect Regression (FEM) technique in both models. Several significant findings are supported by the data. First, while using renewable energy flattens carbon dioxide effusion, using non-renewable energy sources increases it. CO2 emissions are affected negatively by gross domestic product but positively by gross domestic product square. These results provide credence to the idea that South Asian countries do experience an Environment Kuznets Curve. Furthermore, foreign direct investment has a beneficial effect on CO2 emissions, lending credence to the Pollution Haven Hypothesis. Model 2 instead finds that both renewable and non-renewable energy consumption contributes to economic expansion. Gross Fixed Capital Formation and foreign direct investment also contribute to economic growth in this area. Finally, Inflation retards economic expansion.

As the underlying institutional design for enterprise risk management, it is important to study whether and how internal control affects enterprise technological innovation in the current context of increased economic policy uncertainty. Based on the principal-agent theory and information asymmetry theory, this paper explores the impact of internal control on corporate technological innovation using the listed company data from 2009-2019 CSMAR database, and obtains the following research conclusions: (1) the quality of internal control positively affects the corporate technological innovation. (2) The operational risk plays an intermediary role in the relationship between the internal control affecting the corporate technological innovation. (3) The degree of market competition positively moderates the impact of internal control on enterprise technological innovation. (4) Relative to non-stateowned enterprises and non-high-tech enterprises, the quality of internal control of state-owned enterprises and high-tech enterprises has a more significant impact on enterprise technological innovation. This paper enriches the consequences of the study of internal control on the one hand, and on the other hand, it provides a new perspective for improving technological innovation, and it provides certain guidance for further improving the level of corporate governance.

By an endogenous growth model with a two-period overlapping generations structure, I examine the existence of a budget deficit in an economy that endogenously grows by investments of firms. The consumers leave bequests to their descendants and hold money as a part of their savings. I use a Barro-type utility function, where people include the utility of their children in their own utility. The main results are as follows. 1) A budget deficit is necessary for full employment under constant prices. 2) Inflation is induced if the actual budget deficit is greater than the value at which full employment is achieved under constant prices. 3) If the actual budget deficit is smaller than the value which is necessary and sufficient for full employment under constant prices, a recession occurs. Therefore, a balanced budget cannot achieve full employment under constant prices. I do not assume that the budget deficit must later be made up by a budget surplus. I use a Barro-type utility function to prove the necessity (or inevitability) of a budget deficit instead of the neutrality of government debt. In the appendix of this paper, I show that if money, as well as goods, are produced by capital and labor, a budget deficit is not necessary for full employment under constant prices.

Educational equity is the foundation of social equity, and education equalization is one of the serious issues to be solved by the government. This work considers one education equalization reform conducted by Suzhou Industrial Park of China, namely, the comprehensive "five to nine" (CFTN) housing purchase admission qualification adjustment policy, as an example and uses the resold housing transaction data to identify the effect of the equalization policy by the difference-in-differences (DID) method. Based on this natural experiment, the quantitative assessment results show that (1) the CFTN policy has a significantly positive effect on housing prices in nine-year consistent (NYC) school districts that belong to high-quality school districts; (2) the CFTN policy has no significant effect on housing prices in non-NYC consistent school districts that belong to ordinary school districts. These results uncover that the one-size-fits-all CFTN policy can only obtain significant housing price equilibrium effects in school districts above a certain level of education quality. For regions with backward education levels, the policy is ineffective. For these regions, continuously increasing high-quality educational resources and increasing educational service levels are essential solutions to reduce educational inequality.

Based on the panel data of western central-cities from 2002 to 2021, this paper uses the intermediary effect model to analyze the relationship between urban internationalization, innovation ability and urban competitiveness. It is found that: (1) The internationalization of western central-cities has a positive and direct impact on the promotion of urban competitiveness, which has a significant impact on economic strength and infrastructure, and a weak impact on government efficiency and market efficiency The marginal growth effect of internationalization on urban scale will gradually decrease with the improvement of urban development level. (2) The continuous promotion of city internationalization can promote the innovation ability to enhance the competitiveness of the city. Compared with the internationalization of cities, the influence of innovation ability on the competitiveness of cities is small, and the innovation ability of western central-cities and each city is weak. The scale effect has become the main motivation to promote the competitiveness of cities. (3) In the process of internationalization of western central-cities, innovation ability has a part of intermediary effect on the improvement of urban competitiveness, and the effect on urban “hard environment” is significantly greater than that on urban “Soft-environment”. The results of direct and indirect impact tests show that the impact of the process of internationalization of western central-cities on urban competitiveness is exogenous.