Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Gold has been traditionally well recognized as a safe heaven for financial markets. Lately, Bitcoin has been gradually considered as a popular alternative. Since the outbreak of COVID-19 in early 2020, it has become even more necessary and critical to examine the diversification capability of them to hedge financial risks associated with an unexpected crisis comparable to the pandemic. This paper hence employs the wavelet analysis, complemented by the multivariate DCC-GARCH approach, to measure the coherence of the gold and Bitcoin prices with six representative stock market indices, three for developed economies and three for emerging economies, all of which are heavily affected by the pandemic. To have a more balanced and comprehensive analysis, two-year data are used, spanning from 12th April 2019 to 15th April 2021, which covers approximately one year before and one year after the announcement of the COVID-19 pandemic. The results suggest that the returns of both gold and Bitcoin are generally not strongly correlated with the market returns of all six indices, particularly for short-term investment horizons. That is, investors in all six indices can benefit through gold, as well as Bitcoin, in terms of hedging. Meanwhile, compared with Bitcoin, gold shows to be less correlated with the indices, particularly for long-term investment horizons. The findings hence suggest that gold and Bitcoin offer diversification benefits to investors in the market indices during a crisis such as the COVID-19 pandemic, especially for short-term investment horizons. The study also reminds policymakers thinking beyond the pandemic about the future of the earth, including air pollution and health, for sustainable development of the whole world.

This paper provides a thorough review of the shifting landscape of economic analysis, spotlighting recent trends and predicting future paths. While traditional economic models remain key for interpreting economic activity, they are being supplemented by fresh methods and cross-disciplinary viewpoints. The increased attention to inequality studies, using advanced statistical techniques and unique data sources, underscores the growing emphasis on fairness and distribution within economic analysis. The incorporation of behavioral elements into economic models also expands our comprehension of economic decision-making and market results. Notably, the emergence of computational economics-integrating artificial intelligence (AI), big data, and machine learning into economic scrutiny-represents a major development. Often referred to as ’smart economics,’ this field employs technology to formulate, address complex economic dilemmas, and perceive economic activity in unconventional ways. Yet, the application of AI and machine learning in economics introduces new hurdles around data privacy, algorithmic bias, and the transparency of model outcomes. The impact of the digital revolution on economic analysis is significant, as the advent of computational economics and the surge of big data are transforming research techniques and policy implications. Concurrently, the advent of the circular economy indicates a radical shift in our perspective on economic sustainability, carrying considerable implications for environmental policy and business tactics.  In the future, it’s anticipated that these trends will further modify the realm of economic analysis, with AI and machine learning integration, emphasis on sustainability and fairness, and the influence of big data becoming more pronounced. As these changes take place, it’s imperative for researchers, policymakers, and practitioners to remain adaptable and flexible, prepared to capitalize on the opportunities and tackle the challenges these trends present.

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.

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.

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.

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.

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.

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).