Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

BACKGROUND: A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. METHOD: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. RESULTS: We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. CONCLUSION: These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

Financial development, resource richness, eco-innovation, and sustainable development: Does geopolitical risk matter?

Financial development and geopolitical risks can significantly affect sustainable development. However, the roles of these factors in sustainable development are rarely investigated. Thus, this study takes into account the role of geopolitical risk while exploring the effects of financial development, natural resource rents, and eco-innovation on sustainable development in the Organization for Economic Co-operation and Development (OECD) countries. To this end, yearly data from 1990 to 2019 is analyzed using advanced econometric tests. The Common Correlated Effects Mean Group (CCEMG) results indicate that financial development and eco-innovation are significantly and positively related to sustainable development. Natural resource rents have a detrimental impact on sustainable development which confirms the presence of the resource curse hypothesis in OECD countries. Furthermore, the results revealed that controlling geopolitical risk is useful in fostering sustainable development. Lastly, the panel Granger causality test unveiled one-way causality from financial development, eco-innovation, natural resource rents, and geopolitical risk to sustainable development. Moreover, causalities are found from geopolitical risk to financial development, eco-innovation and natural resources. These findings suggest that OECD countries should prioritize financial development and eco-innovation policies for sustainable development while mitigating the negative effects of natural resource rents. The geopolitical risk can harm sustainable development, so policymakers should promote international cooperation and risk-sharing.

Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism.

Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales. Mucor lusitanicus, a member of Mucorales, is commonly used as a model to understand disease pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of M. lusitanicus. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of Phycomyces blakesleeanus, with only one Tec homologue. tec1 and tec2 overexpression in M. lusitanicus increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene rfs, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore, tec1- and tec2-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δgpb1) increased cAMP-PKA activity, downregulation of both tec genes, decreased both virulence and hyphal development, but tec1 and tec2 overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δgpb1. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of M. lusitanicus.

Institutional quality, oil price, and environmental degradation in MENA countries moderated by economic complexity and shadow economy.

This paper aims to analyze the link between environmental degradation and institutional quality and the price of oil moderated by economic complexity and the underground economy. We use quantile regressions with annual panel data for 15 countries in the Middle East and North Africa during 1995-2021. The findings indicate that institutional quality, economic complexity, and output positively and heterogeneously impact environmental degradation. However, the square of production has a negative impact, confirming an inverted U relationship between production and environmental degradation. Likewise, we find that the price of oil and the underground economy have a negative and heterogeneous impact on environmental degradation. Based on our results, a potential recommendation for policymakers is that the institutional framework of Middle Eastern and North African countries should be accompanied by a more significant concern for the environment instead of prioritizing extractive growth that is detrimental to the environment's environmental sustainability. Likewise, economic diversification will mitigate environmental degradation and improve formal employment. Our findings are relevant to policymakers and researchers interested in promoting ecological sustainability.

Does globalization mitigate environmental degradation in selected emerging economies? assessment of the role of financial development, economic growth, renewable energy consumption and urbanization.

While the acceleration of globalization in newly developing (emerging) economies contributes positively to economic developments on the one hand, it is a research topic that can have an impact on environmental pollution on the other hand. Therefore, this study analyzes the impact of globalization on environmental pollution for 14 emerging economies in the 1991-2018 period by including economic growth, financial development, renewable energy consumption, and urbanization in the ecological footprint model. In addition to the AMG forecaster, Driscoll-Kraay, PCSE, and FGLS estimation techniques are used for long-term forecasting. Causal linkages among variables are analyzed by the Dumitrescu-Hurlin panel bootstrap causality test. The findings show that the series are cointegrated, that is, a long-term relationship between the variables. In the long term, globalization and renewable energy consumption reduce environmental pollution, while economic growth and financial development play a role in encouraging environmental pollution. Causality analysis enumerates a causality from economic growth and financial development to environmental pollution, as well as a two-way causality between globalization and environmental pollution and renewable energy consumption and environmental pollution. Empirical findings can offer important implications for policies that will reduce environmental pollution in these countries.

The nexus between government spending, economic growth, and tourism under climate change: testing the CEM model for the USA.

This study examines the impact of government spending, income, and tourism consumption on CO2 emissions in the 50 US states through a novel theoretical model derived from the Armey Curve model and the Environmental Kuznets Curve hypothesis. The findings of this research are essential for policymakers to develop effective strategies for mitigating environmental pollution. Utilizing panel cointegration analysis, the study provides valuable insights into whether continued increases in government spending contribute to higher pollution levels. By identifying the threshold point of spending as a percentage of GDP, policymakers can make informed decisions to avoid the trade-off between increased spending and environmental degradation. For instance, the analysis reveals that Hawaii's tipping point is 16.40%. The empirical results underscore the importance of adopting sustainable policies that foster economic growth while minimizing environmental harm. These findings will aid policymakers in formulating targeted and efficient approaches to tackle climate change and promote long-term environmental sustainability in the United States. Moreover, the impact of tourism development on CO2 emissions varies across states, with some US states experiencing a decrease while others see an increase.

Non-linear effect of manufacturing on an environmental pollution index in Latin America.

Manufacturing is one of the primary sources of environmental pollution due to the emission of polluting gases and waste generation. This research aims to examine the manufacturing industry's effect on an environmental pollution index in nineteen Latin American countries using non-linear methods. The youth population, globalization, property rights, civil liberties, the unemployment gap, and government stability moderate the relationship between the two variables. The research has a temporal coverage between 1990 and 2017 and uses threshold regressions to verify the hypotheses. In order to obtain more specific inferences, we group countries according to the trade block and geographic region to which they belong. Our findings indicate that manufacturing has limited explanatory power for environmental pollution. This finding is supported by the fact that the manufacturing industry in the region is scarce. In addition, we find a threshold effect on the youth population, globalization, property rights, civil liberties, and government stability. Consequently, our results highlight the importance of institutional factors in designing and applying environmental mitigation mechanisms in developing regions.

Renewable energy, economic freedom and economic policy uncertainty: New evidence from a dynamic panel threshold analysis for the G-7 and BRIC countries.

This study aims to demonstrate the impact of renewable energy consumption (REC) on environmental degradation using the EKC hypothesis testing for the BRIC and G-7 countries. Two EKC models were created and tested, with Model 2 including REC and other independent variables such as economic freedom (EF) and economic policy uncertainty (EPU), which affect the level of renewable energy consumption and CO2 emissions. Empirical findings indicate that the EKC hypothesis is verified faster in the REC-EF-EPU-based EKC model (Model 2) than in the EF-EPU-based EKC model (Model 1) for G-7 countries since the turning point takes place earlier in Model 2 than in Model 1 with REC. This suggests that renewable energy consumption accelerates the reduction of CO2 emissions. Moreover, this earlier turning point results in lower environmental cleaning costs, less time vesting, and saving resources and money for G-7 countries. However, the study found no evidence supporting the EKC hypothesis for the BRIC countries.

Is environmental sustainability transmissible? Transportation-based environmental taxation spillovers for sustainable development.

Environmental sustainability investigation has been a hotly debated topic of the modern literature; however, past studies have primarily overlooked its transmissibility or spillover outreach across economies. Herein, we investigate the novel aspect of whether transportation-based environmental taxation spatially induces spillover impacts across Italy, Germany, and France over the 1994-2020 period by employing a simultaneous spatial equation with multi-country dynamic stochastic general equilibrium modeling (DSGEM) framework. Transportation-based environmental taxation of the domestic economy negatively impacts its own investment and consumption, while it impacts the economy of neighboring economies positively. Change in output and investment in the domestic economy can be well explained by the environmental volatility of the domestic economy, whereas the environmental volatility of neighboring economies does not contribute much to explain the change in investment and output of the domestic economy. Volatility in pollution discharge occurs more by environmental volatility in the neighboring economy than in the domestic economy, and validating that environmental sustainability is transmissible across regions and economies. It urgently calls for environmental protection policies integrated and coordinated across the countries and regions to spread and capitalize on environmentally and economically favorable and sustainable effects globally. Achieving the spatially transmitted positive environmental and economic outcomes would help strengthen the Sustainable Development Goals (SDG), with a particular focus on Climate Action (SDG13), Sustainable Production and Consumption (SDG12), and Affordable and Sustainable Energy for All (SDG7).

Determinants of environmental quality in India: evidence using the bootstrapped ARDL model with structural breaks.

This current study examines the impact of renewable energy consumption, agriculture, and globalization on carbon emissions in India over the period from 1980 to 2018. For long-run estimates, we apply Gregory-Hansen's co-integration test, bootstrap ARDL approaches, fully modified ordinary least squares, and dynamic OLS. The empirical results of long-run estimates indicate that a 1% increase in renewable energy consumption, agriculture, and economic globalization will increase carbon emissions by 0.764%, 1.675%, and 0.517%, respectively. Moreover, this study confirms the detrimental effect of these variables on carbon dioxide emissions. Economic globalization coefficients indicate that the scale effect is valid in India. The 2002 economic crisis slowed down the country's growth rate, which reduced the ecological pollution. Several policy recommendations are derived from the empirical findings.

Metformin, a biological and synthetic overview.

Metformin is the most widely known anti-hyperglycemic, officially acquired by the USA government in 1995 and in 2001 it became the most prescribed treatment for type II diabetes. But how did it become the must-use drug for this disease in such a short period of time? it all started with traditional medicine, by using a plant known as "goat's rue" for the reduction of blood glucose levels. Its use arose in 1918 and evolved to the metformin synthesis in laboratories a couple of years later, using very rudimentary methods which involved melting and strong heating. Thus, a first synthetic route that allowed the preparation of the initial metformin derivates was established. Some of these resulted toxics, and others outperformed the metformin, reducing the blood glucose levels in such efficient way. Nevertheless, the risk and documented cases of lactic acidosis increased with metformin derivatives like buformin and phenformin. Recently, metformin has been widely studied, and it has been associated and tested in the treatment of type II diabetes, cancer, polycystic ovarian syndrome, cell differentiation to oligodendrocytes, reduction of oxidative stress in cells, weight reduction, as anti-inflammatory and even in the recent COVID-19 disease. Herein we briefly review and analyze the history, synthesis, and biological applications of metformin and its derivates.

Analyzing the role of green innovation and public-private partnerships in achieving sustainable development goals: a novel policy framework.

The environment's quality is the cornerstone for every country's long-term growth. Pakistan, like other countries, is embracing modern, efficient technologies to build a sustainable environment following the SDGs. In this situation, policymakers and experts have emphasized more on environmental factors. To do this, the study explores the impact of green innovation (GI), public-private partnerships in energy (PPP), energy use (EU), economic development (ED), and power prices (PP) on CO2 emissions in Pakistan from 1980 to 2019. The research uses a novel econometric technique for estimating environmental factors, notably the dynamic autoregressive distributed lag simulations (ARDLS) model and spectral frequency domain causality (SFDC), to examine positive and negative shocks for the prediction of the short-, medium-, and long-run impact of selected determinants, respectively. Additionally, robustness checks were performed using the fully modified OLS (FMOLS), dynamic OLS (DOLS), and canonical cointegrating regression (CCR) estimations. The short and long-term empirical findings indicate that GI lowers emissions; nevertheless, PPP, EU, and ED have a significant impact on emissions in the short run, while the EU increases emissions in the long run. PP, on the other hand, reduces emissions both short and long-term. The FMOLS, DOLS, and CCR estimations indicate significant discoveries. Additionally, the SFDC finding supports the long, medium, and short-term causation theories. This research advocates green innovation for a greener manufacturing process and PPP investment in renewable energy. In addition, the Pakistani government considers these variables while designing a comprehensive protracted environmental plan to meet SDGs 7 and 13.

Are economic growth and environmental pollution a dilemma?

For the first time, this study introduces-proposes using the Armey curve hypothesis (ACH) for testing the environmental Kuznets curve hypothesis (EKCH) in the relevant literature. The rationale for this new proposed methodology is that both hypotheses are expected to have similar inverted U-shaped curves. Hence, we combine the aforementioned hypotheses to obtain a single composite model. This single model may allow us to calculate a maximum (optimum) level of government expenditures that will increase or decrease CO2 emissions for USMCA (the USA-Mexico-Canada Agreement) countries. To this end, our study employs an augmented mean group (AMG) estimator. The results demonstrate that the EKCH is verified by way of the AC model only for Mexico. Additionally, with the advantage of this approach, we calculated the optimal government spending level, which will increase both per capita real GDP (RGDPPC) and CO2 emissions in this country by around 26.4% of RGDPPC. This level of spending will be a kind of threshold point for the Mexican government's policymakers. Hence, they will know that if they continue to spend more than this level, both the RGDPPC and CO2 emissions will decrease, implying either a lower RGDPPC or a cleaner environment. The primary purpose of the proposed methodology in this study is to reveal the possible effects of the government's economic growth-oriented increased public expenditures on the environment in a single composite model. In other words, the relationship between economic growth and the environment is approached from the perspective of public spending, and it is reminded that governments should have harmonious and sustainable public spending policies for both economic growth and a cleaner environment.

A novel EKC perspective: do agricultural production, energy transition, and urban agglomeration achieve ecological sustainability?

We aim to analyze the existence of a novel agricultural production-augmented environmental Kuznets curve (EKC-AP) theory for energy transition, urban agglomeration, and financial depth. To conduct this research, we use a global panel of selected 54 countries belonging to low, medium, and high levels of economic development from 1971 to 2017. Since our data are distributed into three development levels, it is highly likely to face cross-sectional dependence across the countries within and between the development levels, which may provide biased empirical results. To outpace such possibility, we employ advanced econometric strategies, which are robust to cross-sectional dependence and slope heterogeneity issues. We found that agricultural production, energy transition, urban agglomeration, financial depth, and ecological degradation experience a long-term cointegrating equilibrium association. We also confirm that exists an EKC-AP linkage of agricultural production with ecological degradation in highly developed economies, while those at the low and medium levels of development reveal a positive exponential and monotonic impact, respectively, of agricultural production on ecological degradation. The energy transition is found to promote ecological sustainability in developed countries through technique impact, while it deteriorates the ecological quality in countries at the medium development level. Moreover, urban agglomeration adversely impacts the ecological quality in the economies at low and medium development levels, whereas it improves the ecological sustainability in developed economies. Besides, financial depth proves harmful to ecological sustainability, with less subtle effects in developed economies. Based on our findings, for countries at low and medium levels of development, we propose advancing farming techniques using ecologically friendly technologies, promoting green energy transition, expanding the share of the services sector, and providing green financial systems to support green investment projects to achieve the Sustainable Development agenda of the United Nations.

Role of the nonribosomal peptide synthetase siderophore enzyme (Rfs) of Mucor lusitanicus in controlling the growth of fungal phytopathogens.

Dimorphic species of Mucor, which are cosmopolitan fungi belonging to subphylum Mucoromycotina, are metabolically versatile. Some species of Mucor are sources of biotechnological products, such as biodiesel from Mucor circinelloides and expression of heterologous proteins from Mucor lusitanicus. Furthermore, Mucor lusitanicus has been described as a model for understanding mucormycosis infections. However, little is known regarding the relationship between Mucor lusitanicus and other soil inhabitants. In this study, we investigated the potential use of Mucor lusitanicus as a biocontrol agent against fungal phytopathogens, namely Fusarium oxysporum f. sp. lycopersici, Fusarium solani, and Alternaria solani, which destroy economically important crops. Results showed that aerobic cell-free supernatants of the culture broth (SS) from Mucor lusitanicus inhibited the growth of the fungal phytopathogens in culture, soil, and tomato fruits. The SS obtained from a strain of Mucor lusitanicus carrying the deletion of rfs gene, which encodes an enzyme involved in the synthesis of siderophore rhizoferrin, had a decreased inhibitory effect against the growth of the phytopathogens. Contrarily, this inhibitory effect was more evident with the SS from an rfs-overexpressing strain compared to the wild-type. This study provides a framework for the potential biotechnological use of the molecules secreted from Mucor lusitanicus in the biocontrol of fungal phytopathogens.

Transport infrastructure, economic growth, and transport CO2 emissions nexus: Does green energy consumption in the transport sector matter?

Attaining Sustainable Development Goals (SDGs) is important to control the adverse impacts of climate change and achieve sustainable development. Among the 17 SDGs, target 13 emphasizes enhancing urgent actions to combat climate-related changes. This target is also dependent on target 7, which advocates enhancing access to cheap alternative sustainable energy. To accomplish these targets, it is vital to curb the transport CO2 emissions (TCO2) which increased by approximately 80% from 1990 to 2019. Thus, this study assesses the role of transport renewable energy consumption (TRN) in TCO2 by taking into consideration transport fossil fuel consumption (TTF) and road infrastructure (RF) from 1970 to 2019 for the United States (US) with the intention to suggest some suitable mitigation policies. Also, this study assessed the presence of transport environmental Kuznets curve (EKC) to assess the direction of transport-induced growth. The study used the Bayer-Hanck cointegration test which utilizes four different cointegration techniques to decide cointegration along with the Gradual Shift causality test which considers structural shift and fractional integration in time series data. The long-run findings of the Dynamic Ordinary Least Squares (DOLS) test, which counters endogeneity and serial correlation, revealed that the transport renewable energy use mitigates as well as Granger causes TCO2. However, transport fossil fuel usage and road infrastructure enhance TCO2. Surprisingly, the transport EKC is invalid in the case of the US, and increased growth levels are harmful to the environment. The association between TCO2 and economic growth is similar to a U-shaped curve. The Spectral Causality test revealed the growth hypothesis regarding transport fossil fuel use and economic growth connection, which suggests that policymakers should be cautious while decreasing the usage of transport fossil fuels because it may hamper economic progress. These findings call for revisiting growth strategies and increasing green energy utilization in the transport sector to mitigate transport emissions.

The nexus between environmental strategy and environmental performance: analyzing the roles of green product innovation and mechanistic/organic organizational structure.

The relationship between environmental strategy and environmental performance has been extensively analyzed in the environmental management literature. However, this relationship is spurious due to the inconsistence outcomes, lack of intervening mechanism, and scarcity of appropriate context. This study undertakes these considerations by exploring the underlying moderation-mediation mechanism through which proactive corporate environmental strategy affects corporate environmental performance. The hypotheses of the study were empirically tested on the data gathered from 147 ISO 14001:2015 certified firms in Pakistan. The data was statistically validated and then tested with Bootstrapping method using Preacher and Hayes Process Macros. The findings of the study revealed that a proactive corporate environmental strategy predicts corporate environmental performance through green product innovation. Moreover, the moderation hypothesis of the organizational structure variable in the nexus between proactive corporate environmental strategy and green product innovation was not supported in the full sample, whereas the split sample based on organizational size indicated moderation effects in the small firm's sample. The findings of the study carry important implications for firms related to corporate environmental strategy and green product innovation strategy.

Globalization and renewable energy use: how are they contributing to upsurge the CO2 emissions? A global perspective.

The present study major aim was to examine the impact of globalization, economic growth, population growth, renewable energy usage and nuclear energy on CO2 emissions globally by taking the annual data varies from 1985 to 2020. Stationarity among study variables were tested via unit root testing, while nonlinear autoregressive distributed lag (NARDL) technique was used to demonstrate the linkages among variables with the estimation of long-run and short-run. Study results reveal that both in the short run and long run, negative globalization and economic growth shocks positively and negatively influence CO2 emissions, respectively. Besides, higher population growth is found to positively influence CO2 emissions while renewable energy consumption cannot influence the CO2 emission figures. Lastly, positive and negative shocks to alternative nuclear energy consumption are evidenced to negatively influence CO2 emissions both in the short run and long run. Hence, in line with these findings, several new policies and strategies are recommended for reducing carbon emissions globally.