Cancer, a global health menace, continues to pose significant challenges in terms of incidence and mortality, necessitating innovative therapeutic strategies. Despite existing treatments, the limitations persist, prompting a quest for novel approaches. The emergence of immunotherapy marked a transformative era in solid tumor treatments, yet its efficacy is constrained by adverse effects. Concurrently, the integration of advanced technologies into cancer treatment explores the vast potential residing at the molecular level through gene analysis and manipulation. This review articulates the role of state-of-the-art genome editing technology, notably clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), in overcoming the constraints of immunotherapy for cancers. Unveiling the intricacies of CRISPR-Cas9-mediated genome editing, the review introduces the formidable CRISPR toolbox. A spotlight is cast on the transformative impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy, encompassing knockout and knock-in strategies. The utilization of CRISPR/Cas9 technology in pre-clinical cancer research has demonstrated notable success; however, its transition to the clinical setting remains in the nascent stages of development. This review aims to elucidate the fundamental aspects of CRISPR technology and offer a comprehensive survey of its existing applications while outlining its prospective role in the realm of cancer therapies. Through an exploration of CRISPR's mechanisms, current applications, and anticipated future potentials, this review provides valuable insights into the evolving landscape of CRISPR-based cancer treatment strategies.

The enactment of policies that bolster new research and development (R&D) institutions stands as a pivotal strategy to catalyze urban innovation and development. Adopting a strategic lens of innovation chain management and employing the Differences-in-Differences (DID) method to scrutinize panel data from 43 Chinese cities spanning 2008 to 2019, this study probes the efficacy and underlying mechanisms of policies designed to support nascent R&D institutions in facilitating urban innovation. Empirical findings reveal that policies in support of new R&D institutions have markedly enhanced the three integral stages of the urban innovation chain: research and development, transfer, and application. Furthermore, the innovation ambiance within cities and the innovative activities of enterprises emerge as significant mediators between support policies and the output of urban innovation across these stages. A regional heterogeneity analysis unveils that the impact of support policies on the output of urban innovation diverges across regions, with a notably more pronounced effect observed in the eastern region compared to central and western regions. An objective appraisal of the policy's impact on urban innovation not only aids in delving into the profound implementation effects of policy instruments but also furnishes policy-makers with decision-making references for optimizing the utilization of support policies for new R&D institutions to advance the edification of the national innovation system.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

Parkinson’s Disease (PD) is a prevalent progressive neurodegenerative condition affecting millions globally. Research has found that individuals with PD have a reduced risk of certain cancers, such as colon, lung, and rectal cancers, but an increased risk of brain cancer. Therefore, there is an urgent need for the development of advanced PD diagnostic methods and for investigating the relationships between risk factors, such as lifestyle due to handedness associated with various types of cancers. Recent ad- vancements in magnetic resonance imaging have enhanced PD diagnosis, reducing misdiagnosis and facilitating more accurate disease progression monitoring. Nevertheless, challenges exist, particularly in the distinction of PD between left-handed and right-handed patients over time. This survey provides an overview of contemporary deep learning-based imag- ing analysis methodologies, encompassing both non-longitudinal and lon- gitudinal contexts. We also explore existing limitations and prospects for refinement to gain deeper insights. These insights are poised to inform the development of personalized treatment strategies for PD patients while elucidating the current disparities between deep learning models and their efficacious implementation in clinical practice.

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.

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.

Self-employment is often associated with entrepreneurship and regarded as a driver of innovation, job creation and economic growth. As such, many countries have policies to promote and support self-employment. One mechanism for self-employment to drive job growth is for sole traders to become an employer through hiring employees. However, there are few studies that investigate if solo self-employment helps the transitions into employership. Using the Understanding Society data, this study shows that in the UK labour market solo self-employment does not work as a ‘steppingstone’ to employership. This raises the question why self-employment should be promoted through public policy as in the UK and many other developed countries.

The aim of this study is to solve the problem of labor allocation in cases where the company has fewer employees than the number of existing jobs based on the evaluation of work quality according to multiple objectives. Optimizing labor allocation not only benefits the company by maximizing the use of human resources, but also saves employees' energy. In addition, employees are assigned to tasks that match their skills and qualifications, maximizing their productivity. The research results show that the multi-objective decision-making algorithm based on the Hungarian algorithm is a suitable method to help leaders of companies solve the aforementioned problem text.

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.

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.

The rise of privately issued digital currencies, which primarily serve as alternative investment assets poses a challenge to the traditional financial instruments traded in the financial market. This study examines the dynamic relationship between the major privately issued digital currency (Bitcoin) and two financial market securities in Nigeria. The paper employed Vector Autoregressive (VAR) model and presents three relevant findings. First, the impulse response function indicates the absence of a significant response of the Nigerian financial market to shocks emanating from the Bitcoin market, implying lower connectedness between the two markets. Secondly, the outcome of the variance decomposition reveals a lower contribution of Bitcoin to changes in stock prices and treasury bills, however, stock prices and treasury bills contributed higher impact to each other compared to the contribution of Bitcoin. Thirdly, a weak bi-directional causality between the Bitcoin and treasury bills was observed and a uni-directional causality running from treasury bills and stocks, implying the existence of portfolio rebalancing from the fixed income to the equities market. Despite the weak connection between digital currency and the financial market, the paper recommends that the Central Bank of Nigeria and the Securities and Exchange Commission should maintain monitoring the development of crypto exchanges and continue reviewing the existing policy restricting cryptocurrency transactions through banks to avoid its unsavoury effects.

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.

Ferroptosis, a recently identified form of programmed cell death, is characterized by the accumulation of lipid peroxidation, reactive oxygen species, and elevated free iron levels, involving the regulation of glutathione metabolism, iron metabolism, lipid metabolism, and oxidative stress biology. Tumor metastasis, a critical hallmark of malignancy and a key contributor to cancer recurrence and mortality, has been extensively linked to iron dysregulation, highlighting the potential of agents inducing iron-mediated cell death as promising strategies for preventing and treating metastasis. This review offers a comprehensive understanding the regulatory mechanisms underlying ferroptosis and its crucial role in the three distinct stages of metastasis: invasion, circulation, and colonization.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.

Human factor inputs are key to promoting agricultural modernisation. Traditional economic theory suggests that improving human capital is the key to boosting agricultural productivity, but can this conclusion hold in China's dualistic economic structure? We use Chinese provincial panel data from 2000-2017 to examine the impact of rural human capital inputs on agricultural total factor productivity. We find that, on the whole, rural human capital inputs have a negative effect on agricultural total factor productivity, and that there is a "rural human capital trap". Mechanism analysis reveals that rural human capital inputs, on the one hand, cause labour loss and reduce the quality of agricultural workers, while on the other hand, they may promote the application of mechanization, which has both positive and negative effects on agricultural total factor productivity. Heterogeneity analysis finds that this negative effect is more pronounced in the central region of China because of the serious loss of rural labour. This study provides new policy insights for further improving the structure of rural education inputs and promoting human capital accumulation in agriculture.

Carbon emissions trading is an important part of emission reduction policy tools, and manufacturing is the foundation of a strong country. This paper explores the impact of carbon emissions trading pilot on the high-quality development of manufacturing industry by using the double difference method. It is found that carbon emissions trading can significantly promote the high-quality development of manufacturing industry, in which the government's will of ecological environment governance, technological progress and industrial structure rationalization have significant intermediary effects. Heterogeneity analysis reveals that the impact of carbon emissions trading on the high-quality development of the manufacturing industry is most significant in the western region. Accordingly, the study proposes suggestions on how to further improve China's carbon emissions trading market and realize the high-quality development of the manufacturing industry.

As prices have grown at their fastest pace in recent times, inflation has become a key concern for the macro-policy environment. In many jurisdictions, consumer prices have typically formed the basis for price stability policies. Notwithstanding, producer prices remain an important channel and must be closely watched. We utilise data on Ghana and investigate the causal links between consumer and producer inflation and assess the necessity to include producer inflation target in the monetary policy rule. Our VECM and Granger causality analyses show that consumer and producer prices exhibit very stable long-term relationship and short-term gaps between the two tend to normalise over time. The relationship between consumer and producer prices has not been a one-sided lag structure, even though producer prices lead more than lag consumer prices. We conclude that Bank of Ghana’s monetary policy design that does not distinguish between consumer and producer inflation is less problematic at the moment.

There must be a better match between the supply of financial news graduates in colleges and the media's demand for financial news talents. Based on 300 questionnaires and in-depth interviews from three universities, namely Shanghai University of Finance and Economics, Nanjing University of Finance and Economics, and Jiangxi University of Finance and Economics, this paper uses the interview method to excavate the professional quality improvement path for majoring in financial news students. Results reveal that undergraduates majoring in financial news have problems such as low professional identity, insufficient recognition of the discipline system, poor sense of professional identity, common matching between job selection and majors, and worrying about the status quo of professional literacy. Therefore, the improvement of the professional quality of students majoring in financial news and the reform of the training program needs to drive the professional quality of students in multiple dimensions, change their professional cognitive problems, strengthen their professional identity, and achieve an effective match between supply and demand of financial media professionals.

Liquidity and its associated issues are one of dominant strands in the market microstructure. In this study, microblogging-based behavioral perspective on economic unrest is linked to the market liquidity. The concept of liquidity is examined in terms of price dispersion relative to the quantity traded. The analysis contains the quantification of multiple linear regression, Gaussian distribution technique, and vector error correction methodology. In the economic stability period, the investor’s mood, either in positive manner or pessimistic context, had an influential role on the price impact volume-based liquidity. Meantime, the probability was higher for occurrence of price impact volume-based liquidity in response to the sentiment indicators. In the economic unrest environments, the positive bias investor’s mood was not vigorous enough to influence the dispersion of asset’s prices and trading quantity. Most importantly, the negative bias investor’s emotion was linked to increase the dispersion of asset’s prices relative to the quantity traded. Investors with a lower amount of trading quantity had declined the liquidity in the market. Additionally, there was a higher probability for occurrence of illiquidity in the pessimistic market periods. However, changes in past sentiment series were not associated with changes in pervious liquidity series, either in short run or long run. The findings may be potentially applicable to manage the behavioral perspective of liquidity risk.

"Climate Economics and Finance" has risen to prominence as a crucial field, encompassing three primary dimensions: Climate Economics, Climate Finance, and the Intersection of Climate Change and Financial Markets. The adverse externalities arising from climate change, exemplifying a classic instance of "market failure" within market economic frameworks, have garnered global attention. Subsequently, we delve into the literature across three dimensions: the interplay between climate change and macroeconomics, the nexus of climate change and financial markets, and economic or financial resilience. In conclusion, we outline various promising avenues for prospective research in the realm of climate economics and finance.