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.

Carbon emissions trading is essential for reducing carbon emissions, and its role in regional carbon unlocking needs further clarification. This study uses the difference-in-differences (DID) model and synthetic control model (SCM) to evaluate the carbon unlocking effect of China’s six pilot carbon trading provinces. This study found that (1) carbon lock-in effects in China are mainly influenced by technology lock-in and fixed input lock-in; (2) each province’s overall carbon lock-in level presents a decreasing trend yearly, and the regional distribution presents characteristics of “low in the east and high in the west”; (3) carbon emissions trading pilot policies effectively promote the carbon unlocking effect in pilot regions overall, with Guangdong having the most significant unlocking effect. Conversely, Beijing, Hubei, Chongqing, and Shanghai also had different degrees of carbon unlocking. Finally, (4) an assessment of impact mechanisms indicates that technology and institutions have a significant mediating role in effectively promoting carbon unlocking under the carbon trading policy. Conversely, social behavior has an inverse effect, and fixed assets are not affected by the policy. This study demonstrates the carbon unlocking effect of carbon emissions trading and provides a quantitative reference for implementing carbon emissions trading policies and determining carbon unlocking paths.

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.

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 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.

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.

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.