This paper investigates the degree of inflation persistence across regions in Portugal by analyzing the Consumer Price Index (CPI) growth rates for NUTS II regions. The study employs the Augmented Dickey-Fuller (ADF) test to determine whether the CPI data for Portugal is stationary or non-stationary. The results of the ADF test reveal that the IPC data for Portugal is non-stationary, indicating that inflation exhibits persistence in the long run. The study further assesses the persistence of inflation by estimating an autoregressive integrated moving average (ARIMA) model for each region. The Ljung-Box test is used to test for autocorrelation in the time series data, and the Hurst exponent is calculated to evaluate the presence of long-term memory in the time series data. The study finds that there is significant autocorrelation in the time series data for all regions, supporting the presence of persistence in inflation at the regional level in Portugal. The Hurst exponent also shows that the time series data for each region exhibits a high degree of persistence in inflation. Finally, the study applies the ARIMA model to each CPI division's data and uses the Ljung-Box test to test for autocorrelation in the time series data. The results show that some CPI divisions exhibited higher levels of persistence compared to others. For example, the "Housing, water, electricity, gas and other fuels" division exhibited high persistence, while the "Communication" division exhibited low persistence. This study contributes to the existing literature by exploring regional inflation persistence in Portugal and its implications for policymaking. The results provide insights into the inflation persistence patterns across regional levels in Portugal, by emphasizing the need to consider regional differences in inflation dynamics when formulating effective policy interventions. Understanding the persistence of inflation is crucial for policymakers to ensure price stability and sustainable economic growth.

Less-Lethal Weapons, including electric Tasers, velocity-reduction bullet-capture projectiles, rubber bullets, beanbag rounds, and other less-lethal projectiles used in police departments, federal and local law enforcement agencies, and military policing operations, as well as for private use, are topics of significant debate in recent years. These weapons can reduce collateral damage, reputational risk, and legal exposure while preventing wrongful and unnecessary deaths caused by conventional bullet wounds. Yet, opponents have highlighted concerns regarding the safety and effectiveness of these weapons, as well as their potential to cause injury or even death. While the primary duty of law enforcement officials is to preserve order and execute the law while protecting individual rights, they ultimately achieve these goals by exercising their coercive authority. Society expects police officers to rely on their professional training and judgment when using physical force to defend citizens and themselves or to apprehend criminal suspects. Because police officers must occasionally participate in physical acts of coercion, it is unavoidable that some of these interactions may result in bodily injuries to individuals, including the officers themselves. These injuries have real costs, such as medical treatment, lost wages, municipal liability, court claims and settlements, riots, and legal or even criminal exposure, as well as less-tangible collateral costs, such as the erosion of police legitimacy and public trust, which are more difficult to quantify but arguably more influential in shaping long-term public perceptions than personal injuries alone. Less lethal technology eliminates some of the concerns raised by lethal weaponry. This study reviews the advantages and disadvantages of these less-lethal weapon technologies versus traditional firearms for use by the police force, federal agencies, and military police while also performing advanced analytics to model the valuation and return on investment for a law enforcement organization implementing such technologies.

Occupying a preeminent position as the globe’s most extensive economic corridor, the Yangtze River Economic Belt (YREB) serves as a crucial aquifer for 800 million individuals and harbors almost 50% of the country's paramount water-intensive contaminant producers. The ecological efficiency of these producers within the belt has increasingly come under scholarly scrutiny. Leveraging data from 2004-2012 encompassing 725 such manufacturers and employing the DEA-Malmquist index methodology, this research delineates the eco-efficiency trajectories of these water-centric pollutant producers, shedding light on their spatial-temporal dynamics across the expansive Yangtze Economic Belt. The results are as follows: (1) there’s a discernible enhancement in the eco-efficiency (ML) of these manufacturers situated within the YREB, predominantly propelled by technological change (TC) and shifts in technical efficiency change (TEC); (2) From a spatial perspective, notable disparities emerge in both technological change (TC) and technical efficiency change (TEC) among the belt’s upper, middle, and lower tiers. Intriguingly, the hierarchy for TC and TEC descends as follows: Lower > Upper > Middle; (3) Examining the spatial evolution nuances, 2004 witnessed eco-efficiency distributions ranking from Upper > Middle > Lower. Fast forward to 2012, a marked reconfiguration appears with a distribution pattern of Middle > Lower > Upper.

This study delves into the intricate interconnections among the financial sector, macroeconomic dynamics, and the advancement of sustainable energy production in South Asia. Utilizing data from 1987 to 2022 in Bangladesh, India, Pakistan, and Sri Lanka, the research employs the Structural Vector Autoregressive (SVAR) method to analyze financial market responses. The findings reveal nuanced insights into the complex relationship between economic and environmental factors, fostering a comprehensive understanding of the region's intricate nexus between financial markets and sustainable energy initiatives. In the Economic Growth model, the negative coefficient for CO2 emissions underscores environmental concerns, indicating an inverse relationship with economic growth. Conversely, positive coefficients for non-fossil energy production, Gross Fixed Capital Formation, stock exchange value, and domestic credit emphasize their positive impact on economic growth. A positive GDP coefficient in the CO2 emission model signifies heightened carbon emissions with economic growth, while a negative coefficient for non-fossil energy production suggests potential environmental benefits. The nearly unitary positive coefficient for Gross Fixed Capital Formation highlights its significant role in driving carbon emissions. The Non-Fossil Energy Production model reveals an inverse relationship between GDP and clean energy, suggesting a potential reliance on fossil fuels during economic growth. Positive coefficients for CO2 emissions, Gross Fixed Capital Formation, stock exchange value, and domestic credit highlight factors influencing non-fossil energy production. Long-run stable coefficients affirm variable significance, while a negative error correction term suggests convergence in developing countries. These models offer nuanced insights into the intricate relationships among economic, environmental, and energy variables, guiding sustainable development policies in South Asia.

The purpose of this paper is to examine and elucidate the effect of the announcement of winning a US federal contract by pharmaceutical companies, traded on the NASDAQ stock exchange on the share prices. The analysis is based on a sample of 327 event days from 12 pharmaceutical companies listed on the NASDAQ market for a given period (2010 – 2021). The sample is analysed by using the event study methodology and Capital Asset Pricing Model (CAPM) in order to examine the abnormal returns and cumulative abnormal returns during an event window of 10 days before the event and 10 days after the event. While prior researchers have identified significant positive abnormal returns following different types of contract announcements, this study aims to contribute to the existing literature by exploring the specific impact of the public contract in the pharmaceutical market on market shares. By investigating this unique aspect, the research fills a gap in previous studies and enhances our understanding of the relationship between public contract announcements and market performance. The data collection utilises secondary data from the official open data source of US federal spending information and daily stock prices. The collected data is analysed quantitatively using event study methodology, allowing for statistical examination of abnormal returns, such as ANOVA analysis, t-statistic, beta index, time series analysis and linear regression. The research findings indicate a significant impact of public contract-winning announcements on cumulative abnormal returns, suggesting a positive reaction from the market. However, average abnormal returns within the event window were positive but not statistically significant. These results imply that winning a government contract has a limited impact on the stock market. The implications of this research highlight the importance of public contract announcements in the pharmaceutical industry and their influence on share prices. The findings provide valuable insights for investors and stakeholders, aiding decision-making processes related to investment opportunities and market performance.

Tripartite motif-containing (TRIM) proteins consist of over 80 proteins, the majority of which exhibit E3 ubiquitin ligase activity. E3 ligases have a critical role in various cellular processes by specifically recognizing and ubiquitinating substrate proteins to promote their proteasomal degradation or alter their activities. Numerous studies have indicated that TRIMs are involved in carcinogenesis through various mechanisms. However, the regulatory mechanisms delimitating TRIMs’ function as E3 ligases has not yet been specifically addressed in a previous review article. In this review, we focus on recent advancements in understanding how certain TRIMs function solely as E3 ligases during cancer cell proliferation, apoptosis, and metastasis. We comprehensively summarize the target proteins of TRIMs involved in disordered signaling pathways such as Wnt/β-catenin, PI3K/AKT, NF-κB, p53, ERK, and STAT3, as well as those regulating the cell cycle and glycolysis. Following ubiquitination modification by TRIM E3 ligases, these target proteins either undergo proteasome-mediating degradation, maintain steady levels, or get activated/inactivated. This review provides a foundation for the development of E3 ligase-based cancer treatments.

The manufacturing sector must incorporate digitalization and greening as crucial strategies to attain high level of development in the context of the digital economy, given its significant role in quality of environment. Most of existing studies explore net effect of a single or several factors on the digitalization or greening in the manufacturing industry. Limited investigation has been done to integrate various factors impacting the connection and synchronized advancement of digitalization and greening within the manufacturing. Factors affecting the synergy of digitalization and green change within manufacturing are recognized in this article, and a theoretical framework is established to analyze. FsQCA tool is also put into use to survey configurational cases, which contains synergy degree of green digitalization from 30 provinces’ manufacturing in China. Results show that: (1) Between 2007 and 2020, the development level of digital-green integration in the manufacturing industry shows an upward trend. There are three types of collaborative modes, namely, "industrial robot driven" "market development driven" and "market development driven - industrial robot driven", with each mode consisting of at least one to four equivalent pathways. (2) The marketization level and application of industrial robots are the important external and internal pulling forces that drive the synergy degree of digitalization and green change within manufacturing industry, respectively.(3) The influencing factors of the collaborative mode choice of digital-green development within manufacturing industry are complementary, among which, the degree of marketization is similar to the role of industrial robots in the configuration, which are capable to weaken the negative impact from insufficient government R&D investment support under specific conditions; (4) The non-high collaborative state of digital green in manufacturing industry is mainly due to the low level of marketization, openness, and economic development, as well as the low application rate of industrial robots and software products. This study enriches the theoretical understanding on digitalization and green change of manufacturing industry. Meanwhile, it also provides insights to advance the integrated and synergistic advancement of digital green transformation in manufacturing practice.

Population, as a fundamental element in urban development, often reflects a city's economic development pattern through its spatial distribution and dynamic changes. Studying population spatial distribution is pivotal for bolstering the economic activity capacity in urban agglomerations and guiding regional economic health. Using the Changsha-Zhuzhou-Xiangtan urban agglomeration as a case study, this paper analyzes its overall spatial structure and the spatiotemporal evolution of population at the district and county levels. This analysis utilizes population density, population redistribution index, and population geographic concentration as key indices. Additionally, a spatial econometric model is constructed to assess the impact of economic, social, and environmental factors on population spatial patterns. Findings reveal several key points: (1) Furong District serves as the primary central area, boasting a population geographic concentration of 25.1% in 2021. Tianxin District, Kaifu District, Yuhua District, Shifeng District, Yuelu District, and Hetang District constitute the secondary central areas, while Yutang District, Tianyuan District, Lusong District, Yuhu District, Wangcheng District, and Changsha County form the tertiary level areas. (2) Population density within the Changsha-Zhuzhou-Xiangtan urban agglomeration gradually decreases from Furong District outward. The first central area and sub-central areas experience increasing population density, highlighting a polarization trend in the population distribution. (3) The overall Moran's index for the spatial distribution of population in the Changsha-Zhuzhou-Xiangtan urban agglomeration is significantly positive, indicating a strong spatial autocorrelation and a deepening spatial agglomeration of population distribution. (4) Per capita disposable income, financial expenditure, and education level positively influence the geographical concentration of population in the urban agglomeration, while GDP per capita, road area per capita, and environmental quality exert a negative impact. Notably, the most influential factors shaping population spatial distribution are GDP per capita, disposable income per capita, and air quality.

Purpose: To realize the benefits a Quality Management System (QMS), an organization needs to effectively implement its principles. This includes embracing these principles within an enabling environment. Hence, organizational structure is a critical success factor for adopting quality management systems. This paper aims at understanding how the organizational structure impacts ISO 9001 QMS implementation and vise versa, besides exploring how quality management initiatives affect organizational resilience through parts. Design/methodology/approach: The research deploys a qualitative methodology, with an outsider-insider approach. 32 semi-structured interviews were conducted, plus one final reflective interview. Interview questions dealt with structural constructs: communication, employee engagement, employee empowerment, process/routine-orientation, multidisciplinarity, cross-functionality, expertise-utilization and change-readiness. The questions also dealt with how the organizational structure impacted ISO 9001 implementation and vice versa. Findings: The results show that ISO 9001 implementation was more successful and fruitful under process-orientation and to some degree under semi-process orientation, while it looked inconsistent under routine-orientation. This indicates a significant role played by the organizational structure when it comes to ISO 9001 implementation. More importantly, the results also demonstrate that ISO 9001 implementation managed to improve organizational resilience by consistently driving the organizational structure toward higher levels of process-orientation for process-oriented units, whereas it failed to realize such impact for routine-oriented units. Originality/value: This study is unique as it is the first - within the reviewed literature - to examine the moderating role of the organizational structure between the ISO 9001 standard and organizational resilience. It draws a roadmap for the successful realization of organizational resilience through quality management systems, considering organizational structure constructs.

The clean energy revolution is a global concern. Cross-border collaboration is crucial for sharing knowledge, pooling resources, and tackling complex challenges on a global scale. International partnerships can accelerate innovation by drawing on diverse knowledge and experience from different regions. Access to capital is a key driver of innovation and entrepreneurship in clean energy. Institutional investors and financial institutions increasingly recognize the potential for high returns from the clean energy sector. This research aimed to understand whether "dirty" energies, such as the Brent Crude Spot, WTI, FTSE 350 Oil, Gas & Coal, EURO STOXX Oil & Gas, influence the formation of sustainable energy prices, namely Geothermal Index, Solar Energy Index, NASDAQ OMX Bio Clean Fuels Index, Wind Energy Index, WilderHill Clean Energy Index, during the 2020 Covid-19 pandemic and the Russian invasion of Ukraine in 2022. When comparing the two sub-periods, the results show that the level of autocorrelation in price formation has increased, i.e., the mean rhoDCCA went from 32 to 45, the weak correlation coefficients without trend decreased from 30 to 19, and the anti-persistence has also decreased from 8 to 4. The strong rhoDCCA increased from 2 to 4; during the Tranquil period, the FTSE 350 / EURO STOXX Oil index pairs had a rhoDCCA of 0.76. While in the Stress subperiod, the NASDAQ OMX Bio / Solar Energy pairs had a slope of 0.70, and the FTSE 350 / EURO STOXX Oil indices had a rhoDCCA of 0.91. Evidence shows a notable dissociation between fossil energy prices and sustainable energy sources. This dissociation is characterized by various degrees of influence between fossil energy prices and sustainable energy indices, from low to moderate. This dissociation between fossil energy prices and sustainable energy prices suggests that investments in sustainable energy can offer diversification opportunities.

All things being equal, and in a truly democratic world, one will expect that the fact that women are the majority in almost every single community of the world should guarantee them at least equal control or ownership over resources and enjoy most of the rights and privileges in that particular community. But things seem not to be working that way as evidence from the literature shows that women are always relegated to the background when it comes to the issue of control or ownership over, and sometimes even access to property in most societies which include the right to own and use land. This undoubtedly has a consequence on the productive and overall development of such a community. In recent times, the issue of gender discrimination, disparities, and inequalities has attracted the attention of researchers over the past decade with enormous literature in this area. There are, however, few studies that provide a comparative analysis of the situation between two or more countries. This paper seeks to fill this void of knowledge based on a review of relevant literature on land rights with an emphasis on the situations in Kenya and Tanzania. The results have shown the prevalence of four types of land rights such as communal property rights, non or open-access property rights, state or crown property rights, and private property rights. The results have further indicated that the controversial land rights of Kenya have led to the reduction in the lands of certain groups of people, increasing land disputes, and also discriminating against women in their land rights. In the case of Tanzania, there were several cases of bias against women concerning the ownership of land, especially under the customary system of Tanzania. Issues of discrimination against women were also identified in the inheritance laws of the land which is a paramount feature within the norms and cultures of the people of Tanzania. The lack of equal access to land by women in both countries is found to harm productivity in several sectors of their economies, especially in agriculture. Policymakers are therefore admonished to ensure equal access by both genders to land as this will lead to efficiency in the management and usage of land which is certainly good for sustainability in the development of any economy.

Environmental concerns are increasing and business firms are inclined towards adoption of eco-friendly products and services. They are hiring employees via set of green HRM practices and struggling to become an environmentally sustainable firm. Pakistani food industry is booming day by day. However, less is known about the green HRM practices executed in the fast food industry of Pakistan. Therefore, this research is interested in examining the impact of Green recruitment and selection, green training and development and green performance and compensation management on the P-O fit, affective commitment and green recovery performance in Pakistan’s fast food industry. The moderating effects of transformational leadership will be examined between Green HRM practices and green recovery performance. A sample of 408 employees who are working at different designations were selected to accomplish the purpose of the research. These managers will be selected through convenient sampling technique. There were 21 fast food restaurants (Burger Joints) selected from all over Karachi, few of them includes; KFC, Burger Lab, Burger O Clock, Vintage, Plan B and more. The collected primary data will be tested through the application of structural equation modeling technique. Smart PLS software is used to assess the objectives. The results of the study revealed significant association between Green R&S, Green T&D and P-O fit. A non-significant association is found between Green P& C and P-O Fit. The study affirmed that Affective commitment posit a direct influence on GRP. The Green R&S and Green P&C revealed insignificant impacts on the green recovery performance within the fast food industry. The indirect association was analyzed between P&C, P-O fit, AF and GRP and revealed an insignificant result. Likewise, an indirect association is found between R/S, P-O Fit, AF and GRP. The future researchers are recommended to analysis the remaining elements of GHRM and investigate their impacts on the fast food industry of Pakistan. There is a need to create awareness regarding green HRM practices and their influence on the Green recovery performance in Pakistan. Policy makers are recommended to develop such policies that promotes GHRM in Pakistan.

The rapid growth of renewable solar and wind energy necessitates extensive, long-term energy storage solutions to stabilize the electric grid and address the intermittent nature of these sources. In the absence of cost-effective long-duration, large-scale (LDLS) energy storage, there is a risk of increased disruptive blackouts and brownouts as intermittent energy sources approach 50% of electricity generation. Our analysis underscores volumetric energy density as a pivotal determinant in LDLS energy storage solutions, which is particularly crucial during periods of diminished renewable resource availability, such as the rainy season. Despite emphasis on conventional electric batteries and mechanical storage technologies such as compressed air and pumped hydro for LDLS, their costs pose a significant obstacle to widespread adoption, especially in emerging economies. In this study, we present a groundbreaking approach to LDLS: on-demand electricity generation from carbon-neutral renewable oil, known as "green oil," leveraging Reliance’s innovative catalytic hydrothermal liquefaction (R-CAT-HTL) technology. Our investigation evaluated two distinct sources of green oil production: organic waste streams (e.g., municipal solid waste, agricultural-waste, etc.) and on purpose production of algal biomass. We demonstrate that burning renewable green oil to produce electricity offers a cost-effective solution for large-scale (GWh) long-duration (many days) energy storage, ensuring the stability, reliability, and resiliency of the electric grid. We also demonstrate that minimum 14 days, ideally 30 days energy storage is needed for continuous uninterrupted service, especially critical for manufacturing facilities. Through a meticulous levelized cost of storage (LCOS) analysis comparing green oil with other LDLS technologies reported in literature, we demonstrate the cost effectiveness of green oil. In this model, green oil serves as stored energy, functions akin to a battery and is efficiently converted into electricity through conventional reciprocating engines or next-generation more efficient turbines. Our findings suggest that green oil derived from diverse organic sources is the most economically viable option for GWh-scale storage, particularly when storage requirements extend beyond a single day. This research thus presents a transformative cost-effective solution to the pressing challenge of LDLS energy storage, accelerating a sustainable and resilient energy future.

In the context of digital economy, Hebei Province, as an important province in central China, has a huge manufacturing base and potential, and the development of digital economy has driven the transformation and upgrading of manufacturing industry to a certain extent. In order to better play the driving role of digital economy in the transformation and upgrading of manufacturing industry, this paper establishes an intermediary effect model based on three intermediary variables: enterprise resource allocation ability, enterprise cost and enterprise innovation ability, and conducts an empirical study on the panel data of 11 prefecture-level cities in Hebei Province from 2017 to 2022. The mechanism of digital economy driving manufacturing upgrading in Hebei Province was discussed. The results show that: (1) there is a significant positive correlation between the development of digital economy and the transformation and upgrading of manufacturing industry, which indicates that the development of digital economy has a direct driving effect on the transformation and upgrading of manufacturing industry; (2) There is also a positive correlation between the development of digital economy and the resource allocation ability and innovation ability of enterprises, indicating that the development of digital economy can improve the resource allocation ability and innovation ability of enterprises, and is conducive to the stable development of enterprises in the future; (3) Enterprise resource allocation ability and enterprise innovation ability play a significant intermediary role in the relationship between digital economy development and the transformation and upgrading of manufacturing industry, indicating that digital economy can indirectly accelerate the transformation of manufacturing enterprises' R & D achievements by improving enterprises' resource allocation ability and innovation ability, thus improving enterprises' market competitiveness and increasing enterprises' earnings. Drive the transformation and upgrading of the manufacturing industry. Based on this research conclusion, the government should give full play to the role of guidance and support, and introduce relevant policies to help the digital economy drive the transformation and upgrading of manufacturing enterprises. Manufacturing enterprises should seize the tide of the development of the digital economy, use digital technology to improve their resource allocation ability and innovation ability, enhance core competitiveness, and accelerate the transformation and upgrading of enterprises.

Objective: The DSS was utilized to construct colitis model of mouse. The colitis mice were colonized with gut microbiota. The effects of gut microbial metabolites on colitis were studied. The mechanisms of gut microbial metabolites to improve intestinal immunity were also further explored. Methods: The male BALB/c mice were selected to construct colitis mouse model with DSS and colonized with gut microbiota. The content of short-chain fatty acids in intestinal metabolites of mice during modeling were detected with GC-MS. After the mice were sacrificed, the colon tissue was stained to observe the colitis in different groups of mice. The contents of IL-22 and IL-17 in colon tissue was determined with ELISA method. To study the mechanism of relieving colitis, qRT-PCR and western blotting were used to study the horizontal of Ffar2 gene and pSTAT3 and pAKT in colon tissue, respectively. The congenital lymphocytes were isolated and purified, and the migration ability of the congenital lymphocytes was examined by cell scratch plane migration test. Results: The colonization of the gut microbiota had significant effects on the contents of short-chain fatty acids in the intestinal metabolites of colitis mice, of which the effect on the content of acetic acid and butyric acid was more significant. The colonization of gut microbiota could effectively relieve colitis in mice and effectively promote the secretion of IL-22 in colon tissue. Studying the remission mechanism indicated that colonization of gut microbiota with colitis could effectively promote the expression of Ffar2 gene in colon tissue and increase the expression of pSTAT3 and pAKT protein. The migration ability of the lymphocyte was significantly upregulated in the model group compared with the other groups, demonstrating that DSS can effectively activate the lymphocyte; The migration of congenital lymphocyte in the experimental group was significantly alleviated than that in the model group, but it was up-regulated than that in the positive control group, and the colonic tissue of the positive control group was similar to that of the normal group. Conclusion: The short-chain fatty acids in the intestinal flora metabolites can promote the gene expression of the metabolite-sensitive receptor Ffar2. The effective combination of short-chain fatty acids and Ffar2 receptors can promote the phosphorylation of STAT3 and AKT proteins, effectively promote the secretion of IL-22 in intestinal ILC3 cells, alleviate colitis in mice, and thereby improve their intestinal immune function.

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.

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.

Cloud computing is one of the fastest growing domains of the IT industry, however, the growth rates for each of the models on a global and local (Russian) scale have not been generalized, despite the obvious value of such analysis. Modern business and industry in Russia is going through another period of instability and at the same time is forced to follow the trend of digitalization. That is why a balanced scientific analysis and forecast of the development of cloud technologies is needed, as the main factor in improving business efficiency. The purpose of the study: is to review the main models of cloud services for modern business and industry, describing their capabilities separately and the prospects for the market as a whole. The materials for the study were analytical reports of leading consulting companies and materials from specialized web-sites. Result: The article considers cloud technologies as the main global technological trend, describes popular models of cloud services, their opportunities for business and industry. Russian and global leaders in the provision of cloud services are also described, the growth rates of these markets for each of the models are indicated. The most popular and promising cloud service models in 2022 are: UCaaS, CaaS, SaaS, IaaS, RPAaaS, PaaS. The cloud technology market will show strong growth until 2030, generating both hybrid and absolutely new service models. The private business, industrial and public sectors will increasingly move to cloud services. The main trends in the development of cloud technologies until 2030 are: hybrid cloud, artificial intelligence (AI) and cloud computing, deployment of cloud services in the planetary orbit. The results obtained are very valuable for analysts and industry experts. The above trend analysis provides valuable predictive data to research economists, investors, business and industry leaders and other stakeholders on how the cloud services market will grow in the next 5-7 years. The results of the study also have a general theoretical nature, substantiating the importance of further forecasting the development of this market (especially using mathematical methods).