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.

Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

We offer an extensive analysis of the significance of information within the realm of Gaussian quadratic economies. We build upon the seminal papers of Morris and Shin (2002, 2007) and consider a signal game of incomplete information. Particularly, we question the suitability of partial transparency portrayed by fragmented information in addition to the private signal in terms of welfare effects. We can summarize our findings in two main points. First, fragmented information, in conjunction with a private signal, can reduce the reliance on public signals. Second, a conflicting effect arises between increasing full disclosure and increasing the precision of fragmented (semi-public) information when examining different complex scenarios, involving for example endogenous private information or imperfect correlated signals. For a critical threshold, an optimal communication strategy designed by fragmented information should be implemented whenever that kind of information is acquired at a high precision.

This paper presents an analytical framework to assess the probability of achieving nationally determined contributions (NDC). The prediction model based on the Kaya identity is used to simulate the pathway of carbon emission until the target year. Applying the modified STIRPAT framework (named CO-STIRPAT) to data observed in South Korea shows that the probability that the predicted pathway with existing climate technology will stay above the NDC target pathway is significantly high. The result suggests that it is necessary to design a climate policy to improve energy intensity and carbon intensity by accelerating the advance in climate technology.

This study analyzed whether the level of corporate governance of companies listed on the Brazilian capital market is related to the investment decisions of Brazilian pension funds. We start from the assumption that the corporate governance system mitigates the moral risk, that may arise in the relationship between corporate managers and investors and respective shareholders, Brazilian pension funds. Shareholding dispersion would enable opportunism for corporate managers, making decisions focused on their interests to the detriment of shareholders or investors. The governance system would signal that this behavior would be controlled, signaling safer behavior for investors. Thus, the hypothesis is that the level of corporate governance would attract pension funds that would understand this system as reducing investment risk. To test this, we used panel data, with a sample of 1,582 observations of companies listed on the Brazilian Stock Exchange (B3) from 2010 to 2017. The statistical results show that corporate governance positively correlates with investment in pension funds. This leads to the conclusion that, for Brazilian pension funds, companies' signaling about their corporate governance practices is a risk-mitigating factor. Furthermore, these results allow us to infer that the company's governance level associated with leverage is a differentiating signaling element as the evidence points to a positive relationship.

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.

This paper presents an operational framework for assessing the trajectories of production, energy, emissions, and capital accumulation to ensure the implementation of Nationally Determined Contributions (NDCs). The framework combines widely used methodologies (STIRPAT, system dynamics, and optimization) to simulate the pathways of variables until a target year. The CO-STIRPAT dynamic system allows us to identify the spillover pathways from carbon policy to economic growth based on output optimization principles; to conduct a more systematic analysis of the interconnections between the main drivers that determine carbon emissions; to develop a cost-effective climate policy mix that is a backbone for the right combination of carbon pricing, energy efficiency, and carbon intensity; and to assess NDC targets with respect to ambition gaps, implementation gaps, and feasibility.

Economic globalization has intensified economic volatility around the world, and the importance of economic resilience has become increasingly prominent in the face of rising uncertainty due to frequent domestic and foreign shocks. Based on provincial panel data in China from 2008-2019, a comprehensive indicator system is constructed to measure regional economic resilience (RER), and the impact of financial driver (FD) on RER is explored from staged, pathway and non-linear perspectives. The main findings are as follows. (1) Both national and regional levels of FD and RER show an upward trend, and the impact of FD on RER has an “inverted-U” shape: as the capacity of FD increases, its impact on regional economic resilience shifts from promoting to inhibiting. The RER has significant spatial agglomeration characteristic. (2) Interestingly, staged analysis shows FD can significantly promote RER only when it is in the “recovery stage”. (3) The pathway analysis of its effect on regional economic resilience shows the following characteristics: financial scale > financial efficiency > financial deepening. (4) From different regions, there are significant differences in the effect of FD on the promotion of regional economic resilience: central region > western region > eastern region. Finally, the corresponding suggestions were provided.

This article discusses the pressing need to integrate artificial intelligence (AI) into education to facilitate customizable, individualized, and on-demand learning pathways. At the same time, while AI has the potential to expand the learner base and improve learning outcomes, the development of NACE Competencies and durable skills – communication, critical thinking, creativity, leadership, adaptability, and emotional intelligence - must be purposefully integrated in curriculum design now more than ever. Recent studies have shown that AI-driven learning pathways can achieve outcomes more quickly, but this comes at the cost of the development of durable skills. Therefore, traditional student-to-student and student-to-teacher interactions must be prioritized. As such, this study proposes a balanced approach to curriculum design to ensure the best outcomes for learners, where durable skill development is prioritized alongside subject-specific skills and rote memorization. Additionally, the article highlights the need for a combination of Just in Time Training (JITT) approaches, facilitated by AI technology, to reach the implementation of durable skills. The article concludes by questioning how to develop human skills in an increasingly AI-driven education system and emphasizes the importance of curriculum design and traditional learning approaches in creating a cohesive learning experience that develops durable skills in students. It is necessary to recognize that AI-driven education cannot replace the development of human skills, and that traditional interactions play a crucial role in developing these skills.

Spence’s signaling model (Spence, 1973) suggests that education can signal workers’ unobserved ability to employers thereby mitigating discrimination. There have been several studies concerning education’s impact on labor market discrimination against minority or disadvantaged groups. Our approach in this inquiry is unique in that we utilize the data of PhD recipients, a group of people with the highest education attainment, to test Spence’s theory. Another novelty of this paper is that in addition to examining possible discrimination against women and foreign-born, as has been done in previous studies, we further explore possible discrimination against the physically challenged individuals. Our baseline results show conflicting results that Ph.D. education can reduce discrimination against disability and foreign-born but not against gender. Further analysis by the Blinder-Oaxaca Decomposition shows that the wage gaps of gender and disability come more from the unobserved part than the explained part, while the foreign-born wage gap come more from the observable human capital differences. Since prejudice is an unobserved factor and we know that the disadvantaged groups are likely to suffer from prejudice (Oaxaca, 1973; Blinder, 1973; Montes-Rojas et al., 2017; Deshpande and Khanna, 2018), we conjecture that prejudice might be attributable to the unexplained part of the wage gaps. Furthermore, prejudice might be deeply rooted in one’s mind, thus difficult to remove even with the influence of education. Hence, our results reveal that it would be hard for Ph.D. education to eradicate the discrimination against gender and disability, but not against foreign-born.

 In the past, researchers investigated the immune response acting against mycobacterial antigens in tuberculosis (TB). Several ELISA tests have been conducted for the diagnosis of tuberculosis. Other researchers manipulated 16 kDa antigen from Mycobacterium Tuberculosis to develop a tuberculosis diagnostic test while some others studied the subspecies of M. tuberculosis. In the present study, we explored the possibilities of detecting 16 kDa protein derived from M. tuberculosis, on an interdigitated electrode (IDE). Measurements with Electrochemical impedance spectroscopy and current-volt systems were demonstrated using antibody as the probe.  Further, the involvement of gold nanoparticle for the signal-enhancement and high-performance are evidenced. The specificity in the serum containing samples is used to show the clinical relevancy. 16 kDa antigen used in this experiment is highly reliable for TB diagnosis as it largely expresses and can be implemented in other sensing system.

Many startups look for venture capital (VC) funding to grow their business. Anecdotally, in the Southeast Asia context, startup founders who attended an elite institute of higher learning have greater access to this kind of capital, but this has not been demonstrated quantitatively. We look at a dataset of nearly 800 startups in Southeast Asia who have received VC funding in the last 5 years and look for any correlation between the founder's educational background and the amount of VC funding received. We find that founders who have obtained a postgraduate degree from an elite university receive significantly more VC funding than those who graduated from other universities. Furthermore, this effect is only seen at later stages of funding, not at the seed stage. Potential reasons for this effect could be from stronger signaling of business acumen or technical skill; or better access to funding networks.

Pseudomonas aeruginosa is a common pathogen, and its presence in medical environments and water bodies has attracted widespread attention. Traditional detection methods are usually time-consuming and cumbersome, so it is necessary to develop a rapid and sensitive detection technology. DNase can specifically recognize and cut DNA molecules complementary to its substrate sequence. The researchers took advantage of this property to design various DNase-based sensors for detecting the presence of Pseudomonas aeruginosa. These sensors usually use DNase as a recognition element to identify target strains by hybridizing with specific DNA sequences. When the target strain is present, DNase is activated and begins to catalyze the cleavage reaction, producing a detectable signal. This DNase-based sensor has the advantages of rapidity, high sensitivity, and high specificity. In addition, the researchers also explored combining DNase with nanomaterials, fluorescent dyes, etc. to further improve the performance of the sensor. These improvements have improved the detection ability of the sensor in complex samples, laying the foundation for practical applications. With the continuous improvement of technology, these sensors are expected to be widely used in medical, environmental monitoring and other fields, and provide more efficient and convenient solutions for bacterial detection. This study reviewed the research progress of DNase-based sensors for the rapid detection of Pseudomonas aeruginosa.

Lung cancer is the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and lung adenocarcinoma is the most common NSCLC. Most patients with lung cancer eventually lead to local and metastatic recurrence, including many patients who have completely removed the primary tumor during surgery and have no noticeable metastasis. There are two different deoxynucleotide triphosphate (dNTP) libraries in eukaryotic cells. The de novo synthesis of dNTPs in the cytoplasm is coordinated with the cell cycle and reaches a peak in the S phase, thereby providing deoxynucleotides for the replication of genomic DNA. In contrast, the mitochondrial pool of dNTPs is maintained through the mitochondrial deoxynucleoside rescue pathway throughout the cell cycle and is essential for mtDNA replication. Mitochondria are vital cell powers in assimilation and catabolism. Oxidative phosphorylation (OXPHOS) of mitochondria is essential for the self-renewal of cancer stem-like cells in lung cancer, glioblastoma and leukemia. Thymidine kinase 2 (TK2) and deoxyguanosine kinase (DGUOK) are two mitochondrial deoxynucleoside kinases, which are responsible for the transport of pyrimidine and purine deoxynucleoside in mitochondria. Apoptosis and autophagy are important processes that regulate cell proliferation and death in normal cells and cancer cells. Inducing cancer cell apoptosis and autophagy is an effective means to treat malignant tumors. This review discusses the research progress of the relationship between mitochondrial deoxyguanosine kinase and lung adenocarcinoma cell apoptosis and autophagy.

The study investigates the impact of COVID-19 on African exchange rates, employing a panel dataset over the period 2016-2022 from 13 African economies and employing pooled OLS estimator. The findings reveal a noteworthy positive correlation between COVID-19 levels and exchange rates within the region. However, this association necessitates deeper exploration due to its multifaceted implications, including economic disruptions, government interventions, global market interconnections, regional stability perceptions, and investor behavior. Economic indicators, such as GDP, inflation rate, real interest rate, and unemployment rate, significantly influence exchange rates. While GDP positively impacts exchange rates through economic growth, investor confidence, and trade strength, controlled inflation fosters investor confidence and export competitiveness, positively affecting exchange rates. Moreover, a pronounced positive impact of the real interest rate indicates economic stability, attracting investment and contributing to currency appreciation. Conversely, high unemployment negatively affects exchange rates, signaling economic weaknesses and eroding investor confidence. These findings emphasize nuanced policy responses for managing health crisis-induced economic disruptions and suggest future research directions focusing on specific country-level analyses and multifaceted factors influencing currency valuations within African economies.

Although docetaxel treatment yields a high survival rate for prostate cancer (PCa), resistance eventually develops in many patients. Understanding the underlying mechanisms of docetaxel resistance is essential for improving treatment strategies. Cytokines, which play a role in cell signaling and immune responses, have been implicated in drug resistance mechanisms. The study revealed that interleukin-8 (IL-8) was consistently overexpressed in both docetaxel-resistant PCa cell lines. Thus, the expression levels of cytokines released from docetaxel-sensitive (PC-3- and DU-145) and resistant (PC-3/R-DU-145/R) PCa cells were compared. IL-8 was found to be commonly expressed in resistant cell lines. This finding led to the hypothesis that IL-8 could play a key role in mediating PCa cell resistance to docetaxel. IL-8 siRNA treatment increased docetaxel sensitivity in both resistant cells. To demonstrate the mechanism of IL-8-related resistance, MDR1 expression was evaluated. After IL-8 siRNA treatment MDR1 expression was reduced in both resistant cells suggesting that IL-8 regulates the docetaxel resistance of PCa cells via modulation of multidrug resistance 1 (MDR1). By expanding the knowledge of the cytokines and their effect mechanisms, novel approaches can be developed for the treatment of docetaxel-resistant prostate cancer. Further investigations into the role of IL-8 in docetaxel resistance could offer valuable insights into the development of effective treatment strategies for PCa patients.

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.

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.

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.