Search Results (565)

Background/Objectives: Microtubule-targeting agents remain foundational components of anticancer chemotherapy, yet their clinical utility is constrained by resistance and toxicity. Methods: Here, we present a theoretical exploration of a plausible “dual” binding pocket that spans the α-tubulin pironetin site and the inter-subunit todalam site. Eight virtual chimeric ligands, each merging key pharmacophoric elements of pironetin and todalam, were constructed and covalently docked to Cys316 of α-tubulin. Results: Covalent docking followed by 200 ns all-atom molecular dynamics simulations revealed that two derivatives (compounds 4 and 8) stably occupy the merged cavity, simultaneously anchoring in the pironetin region via Michael addition and in the todalam region via π-stacking and hydrogen bonding. These hybrids preserved the critical hydrogen-bonding networks of both parent ligands and exhibited low ligand RMSD values (~1.5 Å) and compact radii of gyration throughout the simulations, indicating a tight, persistent binding. Estimated HYDE affinities of 1.5 µM for compound 4 and 17.6 µM for compound 8, calculated with SeeSAR, suggest that covalent engagement can compensate for moderate non-covalent binding scores. Conclusions: In summary, our results provide compelling grounds for developing a new class of α-tubulin inhibitors that engage the hybrid pocket, laying a foundation for the structure-guided synthesis of first-in-class dual-site compounds capable of overcoming resistance to conventional microtubule-targeting drugs. Full article

Increasing the level of livability in cities is a topical area both in EU policies and in local urban development, as well as in scientific studies. The aim of this article is to assess the degree if livability of the large housing estates (LHEs) built during the socialist period in the main regional cities of Romania and how adequately they meet the requirements of current urban life. The research focused on assessing the accessibility of these neighborhoods to green spaces and other types of public facilities and services of interest, also taking into account the typology of LHEs. For this, we used mixed research methods, namely GIS remote sensing, fieldwork, and questionnaire surveys, with the results being digitally processed and mapped. This comparative research allowed us to see to what extent each type of neighborhood lends itself to the application of the European Green Deal principles (EGD). In this sense, we mapped the transformations undergone by urban green spaces, as a major dimension of sustainability, and we created an LHE accessibility index, using eight groups of indicators. Based on this index, we assessed the degree of livability and the compatibility of LHEs with some of the EGD principles. We believe that this study can be applied in other regions with similar characteristics, for the analysis of territorial accessibility of public services, in the creation of quality of life registers, or for the planning of spatial components of green cities. Full article

Using survey data from five countries in the Southeast Europe (SEE) region, we examine the factors that contribute to the green career intention. As expected, the prior pro-environmental orientation, as measured by the New Ecological Paradigm scale, is associated with green career intention. In addition, there is also a significant association between prior volunteering and the observed career plans. Other factors, including gender, age, study level, social background, and work-related experiences, did not prove to be empirically significant predictors in this context. There is an interesting, but insignificant, tendency among SEE business students at higher study levels to choose green careers; however, seemingly important career determinants, such as work experience, managerial experience, and entrepreneurial experience, do not appear to matter at all. The examined model explains only a small portion of the variation in career intentions, indicating that a wealth of factors remain to be accounted for in future research. We conclude the study with a discussion of implications for business education in the SEE region and offer recommendations for fostering ESG talent in emerging economies. Full article

Seismic design of reinforced concrete buildings in highly active seismic regions is challenging, as structural members are often oversized due to conservative design practices, leading to inefficient use of materials. This study proposes an optimization methodology based on the Peruvian seismic code E.030, implemented with the OpenSeesPy library for modeling and numerical analysis. The methodology automates the linear analysis of frame structures through the parametrization of member dimensions, span lengths, and material properties. Optimization is carried out using the Hill Climbing algorithm, which iteratively explores design alternatives and verifies compliance with code requirements for interstory drift and base shear. Results show material savings of up to 20% in beams and columns. Although interstory drifts increased by 60–85% compared to the initial configuration, they remained within code limits. The methodology establishes a framework for integrating optimization techniques into the seismic design of reinforced concrete frame buildings. Full article

The increasing global emphasis on sustainable transportation drives the need for strong electric vehicle (EV) charging networks. While national plans set high targets for EV adoption, translating these into practical infrastructure placement poses a significant hurdle. This study tackles this by creating detailed maps to show suitable locations for EV charging stations (EVCS) across the Attica region of Greece. Our main approach combines Geographic Information System (GIS) with Multi-Criteria Decision-Making (MCDM), specifically using the Analytic Hierarchy Process (AHP). After reviewing existing research to find important location factors, we adjusted these to fit the unique urban and social features of metropolitan Athens. We established four main criteria, accessibility, social, energy, and environmental, which were then divided into nine sub-criteria for our analysis. We developed four different models, each applying a unique weighting to these criteria (basic, energy-focused, environmental, and social) to see how various planning goals affect spatial outcomes. These models generated graded suitability maps, highlighting areas with high potential for new infrastructure. Central Athens consistently showed the highest suitability, which matches current research and confirms our method’s reliability. This work provides a useful, repeatable framework for local governments to strategically deploy EVCS, supporting urban planning and helping meet national goals for decarbonization and air quality. Full article

Native communities confronted Eurasian colonialism in ways that reflected their own unique histories, social organizations and cultural values. In this paper, we are interested in how such legacies shaped Indigenous survivance, the active presence of Indigenous peoples on the landscape or the refusal to disappear or assimilate into settler society. We seek to understand the climate changes that Native Alaskan Sugpiaq people faced during the Little Ice Age (LIA; ca. CE 1400–1850), how they responded to those changes prior to Russian incursion, and how new or renewed climate adaptations shaped Sugpiaq survivance. Drawing insight from a new multi-proxy analysis of climate change, ecological dynamics, human population history, archaeology, and ethnohistory of the Kodiak Archipelago, we argue that changes in climate variance during the LIA contributed to Sugpiaq cultural elaboration in the centuries prior to Russian colonialism. Persistent cultural values and relationships with marine resources, adaptations of those relationships under expanded levels of harvesting, and responses to evolving opportunities and political realities were key legacies carried into colonial circumstances by Sugpiaq people. In addition, we see the foundational role of Sugpiaq women in procuring and sharing subsistence foods and the development of regional Indigenous identities as important factors in Sugpiaq survivance in the Russian colonial period. While colonialism introduced novel threats, Sugpiaq people confronted those challenges with the tools and values they inherited from their past, and they persisted through the active deployment of creative and culturally appropriate responses to the co-crises of colonialism and climate unpredictability. Full article

Background/Objectives: Body surface area (BSA) is an important metric that represents human dimensionality and could provide a more accurate representation of body composition. The objectives were (a) to verify the validity of a set of equations based on BSA to estimate lean body mass (LBM), using dual X-ray absorptiometry (DXA) as a reference method and (b) to propose reference values of BSA by anthropometry and LBM by DXA in a regional sample of Chile aged 4 to 85 years. Methods: A descriptive cross-sectional study was performed. The sample size was 5493 participants. Weight and height were measured. BSA was calculated using seven equations. LBM was assessed by DXA. Results: Only three BSA equations (Dubois–Dubois, 1916, Fujimoto, Watanabe, 1969, and Mattar, 1981) best explained LBM. The explanatory power for males was R² = 83 to 84%, and that for females was R² = 69%. The standard error of estimation (SEE) of the three equations showed acceptable values in both sexes. These values ranged from 0.049 to 0.080 in males and from 0.035 to 0.088 in females. The Bland–Altman concordance analysis showed adequate limits of agreement. In men, they ranged from −0.092 to 0.069 m². In females, they ranged from −0.064 to 0.084 m². Reference values for BSA and LBM were constructed using percentiles. Conclusions: This study demonstrated the validity of three equations for estimating LBM in a Chilean sample aged between 4 and 85 years. These results show consistent behavior and acceptable accuracy, especially in the Mattar equation for all ages. However, the Dubois & Dubois and Fujimoto equations could also be an alternative in females. Reference values were generated for BSA and LBM according to age and sex. The results suggest their applicability and usefulness in clinical and public health contexts. Full article

Dengue fever is one of the most important mosquito-borne diseases worldwide. The Association of Southeast Asian Nations (ASEAN) region is a high-incidence area for dengue fever and a primary source of imported cases in China. Based on the Global Burden of Disease (GBD) data, this study statistically analyzed the spatiotemporal distribution of the age-standardized incidence rate (ASR) of dengue fever in ten ASEAN countries from 1990 to 2021. Joinpoint regression was used to analyze long-term trends, and future trends from 2022 to 2031 were predicted. In 2021, the ASR of dengue fever varied widely among ASEAN countries. Singapore had the highest ASR (8715 cases per 100,000 persons). After 2000, countries, such as Brunei Darussalam, experienced short-term outbreaks. From 1990 to 2021, seven countries showed a significant upward trend in the ASR (AAPC > 0, p < 0.05). Predictions indicate that the Philippines will continue to see a rising ASR from 2022 to 2031, and the dengue fever situation in ASEAN countries is severe and heterogeneous. We recommend differentiated control measures according to the ASR level of the source country in China. The results can support the development of Sino-ASEAN collaborative strategies for dengue fever prevention and control. Full article

The market for niche and novelty products in the food industry is growing. However, breaking into the market is tough and reaching the modern-day consumer is harder than ever before. Sorghum, a so-called “ancient grain,” has a chance to be able to compete, but its introduction to human food products needs to be done properly if it is to become a mainstream ingredient. Ten focus groups, with at least two in each of the United States (U.S.) census regions, were conducted to better understand the perceptions, opinions, beliefs, and attitudes for introducing new grain products to the market and specifically regarding grain sorghum. Participants were unfamiliar with sorghum. The few who had heard of sorghum before had difficulty recalling anything about it. When shown a fact sheet on a “new grain” and the nutrition information about the grain, the majority of responses were quite positive. Most consumers were interested in trying products made with the grain and provided various ways the grain (i.e., sorghum) could be introduced to consumers in the United States. A number of terms with potential positive connotations were mentioned by participants that could be used in future research to determine the specific marketability of the grain as an ingredient or in finished products. This qualitative market research demonstrates the open slate that groups such as sorghum commissions, industry, government, and consumer groups have related to sorghum use for consumer food products. It is important to give manufacturers ideas on how best to introduce this “new” grain and to determine which products people would like to see it in. It also is important to understand the marketing options people want to see for a food they have not tried before. Finally, what food advertising options consumers say they pay attention to and which they tend not to focus on is a focus of this research. Full article

Previous research identified three reasons for valuing nature (i.e., the basis for seeing nature as valuable and important): (1) valuing nature for what it gives to humans (instrumental), (2) valuing nature for its own sake (intrinsic), and (3) valuing nature because of the relationship between people and nature (relational). Of these, relational value-bases have been less studied, especially in non-Western cultures. Using a large sample (n = 2618), with participants from five distinct cultural regions (Japan, Taiwan, Italy, France, USA), the present research tests whether a three-factor framework of environmental value-bases generalizes to other cultures. Our findings demonstrate the configural and metric invariance of the recently validated Environmental Value-Bases Scale, indicating that the latent constructs generalize across sub-samples of the five regions and that the measure can be used to test associations between the value-bases and outcomes across cultures. However, we only found partial scalar invariance, suggesting (a) that caution is needed when comparing scale means between cultures and (b) that such tests are most appropriately performed using latent means. This research further contributes to the growing value-basis literature by comparing the latent means for each value-basis between and within each of the five regions and by demonstrating their associations with place attachment. Full article

Liposomal systems are advanced carriers of active substances which, thanks to their ability to encapsulate these substances, significantly improve their pharmacokinetics, bioavailability, and selectivity. This article presents the results of spectroscopic studies for a selected compound from the 1,3,4-thiadiazole group, namely 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol (NTBD, see below in the text), in selected liposomal systems formed from the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Detailed spectroscopic analyses were carried out using electronic absorption and fluorescence spectroscopy; resonance light scattering (RLS) spectra measurements; dynamic light scattering (DLS); as well as time-resolved methods—fluorescence lifetime measurements using the TCSPC technique. Subsequently, based on the interpretation of spectra obtained by FTIR infrared spectroscopy, the preliminary molecular organization of the above-mentioned compounds within lipid multilayers was determined. It was found that NTBD preferentially occupies the region of polar lipid headgroups in the lipid multilayer, although it also noticeably interacts with the hydrocarbon chains of the lipids. Furthermore, X-ray diffraction (XRD) techniques were used to study the effect of NTBD on the molecular organization of DPPC lipid multilayers. Monomeric structures and aggregated forms of the above-mentioned 1,3,4-thiadiazole analogue were characterized using X-ray crystallography. Interesting dual fluorescence effects observed in steady-state fluorescence measurements were linked to the excited-state intramolecular proton transfer (ESIPT) effect (based on our earlier studies), which, in the obtained biophysical systems—liposomal systems with strong hydrophobicity—is greatly enhanced by aggregation-induced emission (AIE) effects. In summary, the research presented in this study, concerning the novel 1,3,4-thiadiazole derivative NTBD, is highly relevant to drug delivery systems, such as various model liposomal systems, as it demonstrates that depending on the concentration of the selected fluorophore, different forms may be present, allowing for appropriate modulation of its biological activity. Full article

Under the dual pressures of climate change and rapid urbanization, extreme heat events pose growing risks to densely populated megaregions. The Guangdong–Hong Kong–Macao Greater Bay Area (GBA), a densely populated and economically vital region, serves as a critical hotspot for heat risk aggregation. This study develops a high-resolution multi-dimensional framework to assess the spatiotemporal evolution of its heat risk profile from 2000 to 2020. A Heat Risk Index (HRI) integrating heat hazard and vulnerability components to measure potential heat-related impacts is calculated as the product of the Heat Hazard Index (HHI) and Heat Vulnerability Index (HVI) for 1 km grids in GBA. The HHI integrates the frequency of hot days and hot nights. HVI incorporates population density, GDP, remote-sensing nighttime light data, and MODIS-based landscape indicators (e.g., NDVI, NDWI, and NDBI), with weights determined objectively using the static Entropy Weight Method to ensure spatiotemporal comparability. The findings reveal an escalation of heat risk, expanding at an average rate of 342 km² per year (p = 0.008), with the proportion of areas classified as high-risk or above increasing from 21.8% in 2000 to 33.3% in 2020. This trend was characterized by (a) a pronounced asymmetric warming pattern, with nighttime temperatures rising more rapidly than daytime temperatures; (b) high vulnerability dominated by the concentration of population and economic assets, as indicated by high EWM-based weights; and (c) isolated high-risk hotspots (Guangzhou and Hong Kong) in 2000, which have expanded into a high-risk belt across the Pearl River Delta’s industrial heartland, like Foshan seeing their high-risk area expand from 3.4% to 27.0%. By combining remote sensing and socioeconomic data, this study provides a transferable framework that moves beyond coarse-scale assessments to identify specific intra-regional risk hotspots. The resulting high-resolution risk maps offer a quantitative foundation for developing spatially explicit climate adaptation strategies in the GBA and other rapidly urbanizing megaregions. Full article

In the context of intensifying climate change, it is particularly important to assess the transformation of spring floods as a key phase of the hydrological regime of rivers. This study provides a comprehensive analysis of the characteristics of maximum runoff in the Zhaiyk–Caspian basin for the modern period and projected changes for 2030, 2040, and 2050 based on CMIP6 climate scenarios (SSP3-7.0 and SSP5-8.5). Analysis of observations at 34 hydrological stations showed a reduction in spring runoff by up to 35%, a decrease in the duration of high water and a reduction in maximum water discharge on some rivers by up to 45%. It has been established that those rising temperatures, more frequent thaws, and reduced autumn moisture lead to lower maximum water discharge and a redistribution of the seasonal flow regime. Scenario projections revealed significant spatial heterogeneity: some rivers are expected to experience an increase in maximum discharge of up to 72%, while others will see a steady decline in maximum discharge of up to 35%. The results obtained indicate the need to transition to an adaptive water management system focused on the regional characteristics of river basins and the sensitivity of small- and medium-sized watercourses to climate change. Full article

The lack of reliable methods for cropland and forest monitoring remains a challenge in the Betsiboka basin and Ankarafantsika National Park (ANP), Madagascar. A key novelty of our study is the comparative analysis of multiple high-resolution datasets for 2017 and 2021 and future projections under five Shared Socioeconomic Pathways (SSPs) from 2020 to 2100 using Google Earth Engine and Python. Results indicate that forest cover has remained below ~9% in the Betsiboka basin and above ~35% in ANP, while cropland stays under 7% in both areas. Inter-dataset agreement showed high overall accuracy (OA = 0.87–0.95), with stronger agreement in ANP (Kappa = 0.68–0.90). FROM-GLC10 and ESA performed best for cropland classification in Betsiboka, while Dynamic World and ESRI were most accurate for forest, particularly in ANP. Projections suggest that by 2100, forest area in Betsiboka may increase by +230% under SSP3 and +300% under SSP5, whereas ANP could see declines up to 39% under SSP1, −2.2% SSP5, and −1.4% SSP3. The predicted minor cropland increase across both regions suggests that forest expansion is unlikely to significantly constrain agricultural land, illustrating the potential for sustainable intensification and agroforestry to address food security challenges. Full article

The equitable allocation of carbon emission responsibility is fundamental to advancing China’s industrial decarbonization, achieving its dual-carbon goals, and realizing regional sustainable development. However, prevailing interprovincial carbon accounting frameworks often neglect the coupled dynamics of economic benefits, energy flows, and ecological capacity, leading to systematic misattribution of industrial carbon footprint transfers. Here, we develop an integrated analytical framework combining multi-regional input–output (MRIO) modeling and net primary productivity (NPP) assessment to comprehensively quantify industrial carbon footprints and their transfers across 30 Chinese provinces. By embedding both the benefit principle (aligning responsibility with trade-generated economic gains) and the energy flow principle (accounting for interprovincial energy trade), we construct a dual-adjustment mechanism that rectifies spatial and sectoral imbalances in traditional accounting. Our results reveal pronounced east-to-west industrial carbon footprint transfers, with resource-rich provinces (e.g., Inner Mongolia, Xinjiang) disproportionately burdened by external consumption, impacting the balance of sustainable development in these regions. Implementing benefit and energy flow adjustments redistributes responsibility more fairly: high-benefit, energy-importing provinces (e.g., Shanghai, Jiangsu, Beijing) assume greater carbon obligations, while energy-exporting, resource-dependent regions see reduced responsibilities. This approach narrows the gap between production- and consumption-based accounting, offering a scientifically robust, policy-relevant pathway to balance regional development and environmental accountability. The proposed framework provides actionable insights for designing carbon compensation mechanisms and formulating equitable decarbonization policies in China and other economies facing similar regional disparities. Full article