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.

Previous literature shows that the price-discovery ability of options market varies substantially over time. Using data of Shanghai Stock Exchange 50 exchange-traded fund options, this paper shows that options prices contribute relatively less to price discovery during low-sentiment periods, but the price-discovery ability of options market remains unchanged during high-sentiment periods. These results suggest that change in aggregate investor sentiment is an important source of the time variation in options’ price discovery ability. Moreover, the options market experiences greater bid-ask spreads when investor sentiment is lower, supporting a “transaction costs mechanism.” This paper fulfills related literature on the time variation in options’ price-discovery ability.

The progression in nanotechnology has revolutionized the biomedical sciences for diagnosis and treatment of diseases like cancer. There have been many kinds of nanomaterials but Inorganic nanomaterials have been considered potential candidates for anticancer activities due to their high biocompatibility, less toxicity, high stability, and high precision in targeting affected cells. Several synthesis approaches have been used to prepared these nanoparticles, such as physical, chemical, and biogenic methods. Due to higher toxicity and adverse effects of chemical methods, eco-friendly way such as biosynthesized inorganic nanomaterials have attained much attention for multiple application particularly treatment of diseases. This review presents a comprehensive and updated knowledge (2015-2023) regarding the cancer treatment. The article first categorizes biogenically synthesized inorganic nanoparticles into three main groups: metallic nanoparticles, metal oxide nanoparticles, and quantum dots and then successful stories related to cancer treatment. This will also provide very effective platform for researchers and academia to detail the biogenically synthesized inorganic nanoparticles’ morphology, their characterization, targeted cancer cells.

Public diplomacy is a significant factor in promoting policy communication, people-to-people bonds, and the protection of foreign assets between two nations, but there is little research on the economic worth of public diplomacy. Python was used to crawl the daily search frequency of "China", "African countries", and related terms to construct the heat index of China-Africa public diplomacy during 2011-2019, and a two-way fixed effect model was developed to examine the impact of public diplomacy on China’s outward foreign direct investment (OFDI) in Africa. The empirical results show that public diplomacy has a considerable favorable effect on China’s OFDI in Africa, and after a series of robustness tests, the basic conclusion still holds. Heterogeneity tests show the investment promotion effect of public diplomacy is more pronounced in sub-Saharan Africa and that the promotion mechanism exhibits the characteristics of poverty alleviation and risk aversion. In addition, the promotion effect of public diplomacy on China’s OFDI becomes greater as time goes on. In terms of impact mechanisms, public diplomacy may promote OFDI by enhancing financing capacity and improving national governance. The research conclusion has policy implications for promoting China-Africa public diplomacy and investment cooperation in the new era.

In China, the land arrangement behavior of over 160 million rural-urban migrant workers is closely related to the optimal allocation of rural land resources and sustainable development of urban and rural areas. Although previous studies show that social capital affects migrant workers’ land arrangement behavior, few empirical studies reveal the relationship between them, and the corresponding interventions remain unclear. Using survey data collected in Henan Province, China, and a multinomial logit model, this study empirically analyzes the mechanism behind the impact of social capital on migrant workers’ land arrangement behavior from the perspective of social capital. Results illustrate that social capital has a significant impact on the land arrangement behavior of migrant workers. The behavior is significantly correlated with the scale of migrant workers’ urban social networks, the degree of urban social trust, and urban belonging. More social capital in urban areas indicates a higher tendency for migrant workers to abandon their land contracting rights and become permanent urban residents. This study reveals the mechanism of social capital affecting migrant workers’ land arrangement behavior and provides a reference for decision-making with respect to guiding migrant workers’ land management behavior for other countries facing similar social problems.

The construction and optimization of a portfolio is a complex process that has been a historically active research area in finance. For portfolios with highly correlated assets, the performance of traditional risk-based asset allocations methods such as the mean-variance (MV) model is limited when numerous assets are correlated. A novel clustering-based asset allocation method, called Hierarchical Risk Parity (HRP), provides an opportunity to mitigate these limitations in portfolio construction. HRP utilizes the hierarchical relationships between the covariance of assets in a portfolio to determine weight distributions, eliminating the need for the inversion of the covariance matrix that is required by most traditional risk-based asset allocation methods. This research examines the viability of Hierarchical Risk Parity (HRP) method in portfolio construction of a US equity portfolio and compares the performances of HRP to traditional asset allocation methods exemplified by the mean-variance (MV) method. The results of this research show that the performance of the HRP method is comparable to the performance of the MV method. Given these findings, HRP provides an advantageous approach for portfolio construction in practical scenarios where correlated assets are present in the portfolios.

This paper explores how the medical expenditure risk affects the households’ portfolio choice across health status theoretically in a life cycle model and empirically using machine learning methods. Medical expenditure risk, as a background risk, has the potential to influence households’ financial decisions. A higher medical expenditure risk leads to a larger fluctuation and more uncertainty in households’ consumption and therefore utility. As a result, risk-free assets become more attractive. Our machine learning analysis provides evidence that aligns with the predictions of the theoretical life cycle model. Specifically, households with better health hold a larger proportion of stocks in their portfolios. Furthermore, when facing increased medical expenditure risk, households in good health demonstrate a greater willingness to invest in safe assets.

We present two approaches to forecasting parameters in the SABR model. The first approach is the vector autoregressive moving-average model (VARMA) for the time series of the in-sample calibrated parameters, and the second is based on machine learning techniques called epsilon-support vector regression (ε-SVR). Using daily data of S&P 500 ETF option prices from January 1, 2014, to December 31, 2018, we first calibrate the daily values of the model parameters from the training sample, then conduct out-of-sample forecasting of parameters and pricing of options. Both approaches produce good fits between the forecasted and calibrated parameters for out-of-sample dates. A comparison study shows that using forecasted parameters as inputs, the SABR model generates better pricing results than assuming constant parameters or using lag parameters. We also discuss the market conditions under which one approach outperforms the other.

Environmental degradation is becoming a fundamental issue as it is directly associated with human lives and environmental sustainability. This research particularly highlights the significance of green transportation taxes in achieving environmental sustainability due to limited available literature considering the environmental sustainability and green transportation taxes nexus. By employing the newly developed QARDL approach, this study is unfolding the linkages of green transportation taxes on transport-based CO2 emissions for Chinese economy spanning 1992 to 2020. The results infer that green transportation taxes to enhance environmental sustainability in the long-run for the highest quantiles, i.e., 0.70 to 0.95. Though, green transportation taxes enhance environmental sustainability in all quantiles in the short-run. Based on these results, the study suggests that the Chinese government and policymakers should increase green transportation taxes that help in combating CO2 emissions, which ultimately enhances environmental sustainability.

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.

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

This study estimates the impact of third-party online payment systems on trade, export, import, and Internet retailing in China. Also, the study examines the financial development mechanism via which third-party payment affects trade, export, import, and Internet retailing in China. By employing a sample of 31 provinces in China covering 2011 to 2018, the findings indicate that, third-party payment drives China’s trade (0.43%), export (0.42%), import (0.47%), and Internet retailing (0.24%). The study also finds that third-party payment complements financial development to positively affect trade, export, import, and Internet retailing in China. The study recommends policymakers promote third-party payment development in China to boost trade, export, import, and Internet retailing.

Peripheral nerve injury is a serious and disabling disease prevalent in the world. It caused by trauma is often accompanied with soft tissue injuries, fractures, infections, etc., and can cause permanent damage. The treatment methods of peripheral nerve injury mainly include traditional microsurgical repair, neurotrophic drug treatment, as well as cuttingedge nerve conduit treatment, nerve stimulation, cell therapy, etc. However, more than 30% of patients with peripheral nerve injury still have poor recovery, including partial loss or complete loss of motor and/or sensory function, muscle atrophy，chronic pain and severe disability, among can lead to permanent disease. Phenolic compounds are secondary metabolites which is the most abundant in plants, consisting of an aromatic ring and one or more hydroxyl substituents, the main groups including flavonoids, phenolic acids, tannins, stilbene and lignans. A lot of studies have shown that natural phenolic compounds have various properties, such as antioxidant, anti-infective, anticancer, anti-inflammatory, etc., and have broad applications in the prevention of heart disease, cancer, diabetes, oxidative stress-related diseases, and neuroprotection prospect. This review discusses the potential applications and molecular mechanisms of natural phenolic compounds its polymer derivatives in the treatment of peripheral nerve injury.

Based on provincial panel data in China, this study is the first to investigate whether industry-university-research collaborative innovation (IURCI) can help to improve factor misallocation. It is found that IURCI can significantly improve capital misallocation and labor misallocation, and the effect has regional differences, which shows that the improvement effect is obvious in areas with factor under-allocation, such as the central and western regions, but not obvious in areas with factor over-allocation, which conforms to the rule of diminishing marginal returns. A regulatory effect model is built to explore the impact of regional heterogeneity, through which we find that after considering three external environmental conditions, including economic development level, academic research level, and marketization degree, the improvement effect of IURCI on factor misallocation undergoes significant changes. The research results show that to deepen the marketization reform of factor allocation, we can start with IURCI. The government should form a sustainable and normalized industry-university-research collaborative innovation ecological mode through pilot cases and adopt measures according to local conditions to ensure the efficient use and reasonable distribution of capital and human resources of enterprises, universities, and scientific research institutions.

The digital transformation provides an opportunity for the development of a green and low-carbon economy. This study used panel data collected from 30 Chinese provinces between 2011 and 2018, and assessed the impact of digitization (Dig) on environmental efficiency (EE). Quantile regression is employed to scrutinize the evolution of the marginal effect. From the perspectives of population and institutional factors, this study empirically investigates nonlinear relationships and potential mechanisms using Hansen threshold and mediation models. The findings reveal several key insights. Overall, levels of digitization and environmental efficiency (EE) are increasing with regional dispersion expansion, indicating a “polarization” characteristic. The impact of digitization on EE exhibits noticeable stage and regional heterogeneity. Analysis of population factors reveals that population structure, population size, and human capital trigger a sharp “marginal increase” of positive effects with single thresholds of 0.8155, 7.2284, and 11.0497, respectively. Analysis of institutional factors highlights the significance of fiscal policy quality (tax proportion), education expenditure, and tax system structure as important intermediaries. Finally, this paper presents corresponding policy implications.

It's critical for environmental governance to understand the effectiveness of policy interventions as well as their working mechanisms. This paper focuses on the vehicle license plate-based management, a sort of policy intervention understudied in environmental governance literature. Specifically, we study the automobile purchase restriction (APR), a major method of license management to address urban air pollution and traffic congestion recently launched by the authorities of China. However, limited studies have quantified the environmental impact of such purchase restriction. Based on the panel data of PM2.5 concentration in 330 cities in China during 1998-2016, this study aims to explore the causal impact of Beijing automobile purchase restriction on air quality, using the regression control method and high-dimensional data regression of machine learning. The average PM2.5 concentration did not decrease but increased because of the purchase restriction. Over time, the deterioration effect on urban air quality will not alleviate. Besides, the restriction cannot enhance urban air quality by decreasing the increase of PM2.5. Despite excluding the impact of driving restriction, the purchase restriction markedly aggravate urban air quality. This paper has some policy implications for policymakers on the impact of urban vehicle license management with caution. Hence, it is essential to promote urban economy, production, and lifestyle to attain the win-win goal of air pollution control and urban development.

Green credit policy (GCP) relies on financial means to promote environmental governance. Whether it can achieve the goals of economic development and environmental protection, especially in the context of different institutional supplies, remains to be scientifically tested. Based on the implementation of China’s Green Credit Guidelines in 2012, this study uses panel data of Chinese companies from 2009 to 2019 to explore the influence of GCP on green technology innovation and the role of institutional supply in it. The results show that GCP is instrumental in promoting green innovation in heavily polluting enterprises, and the promotion effect is heterogeneous based on green patent types, firms’ ownership, and regional financial development levels. Further analysis finds that the supply of environmental protection systems by local governments can strengthen the green innovation effect of GCP. However, the institutional supply of innovation has not yet released a promotional effect. This paper finds that green credit can be used as an environmental governance tool and provides inspiration for local governments to issue environmental protection policies scientifically.

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.

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.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.