ST08 and ST09 are potent curcumin derivatives with antiproliferative, apoptotic, and migrastatic properties. Both ST08 and ST09 exhibit in vitro and in vivo anticancer properties. As reported earlier, these derivatives were highly cytotoxic towards MDA-MB-231 triple-negative breast cancer cells with IC50 values in the nanomolar (40-80nM) range.In this study,we performed whole-genome bisulfite sequencing(WGBS) of untreated (control), ST08 and ST09 (treated) triple-negative breast cancer cell line MDA-MB-231 to unravel epigenetic changes induced by the drug. We identified differentially methylated sites (DMSs) enriched in promoter regions across the genome. Analysis of the CpG island promoter methylation identified 12 genes common to both drugs, and 50% of them are known to be methylated in patient samples that were hypomethylated by drugs belonging to the homeobox family transcription factors.Methylation analysis of the gene body revealed 910 and 952 genes to be hypermethylatedin ST08 and ST09 treated MDA-MB-231 cells respectively. Correlation of the gene body hypermethylation with expression revealed CACNAH1 to be upregulated in ST08 treatment and CDH23 upregulation in ST09.Further, integrated analysis of the WGBS with RNA-seq identified uniquely altered pathways - ST08 altered ECM pathway, and ST09 cell cycle, indicating drug-specific signatures.

Parametric thinking has found wide acceptance in both the building industry and environmental sciences. In the context of environmental urban morphology however, parametric thinking has been neglected. This paper critically assesses environmental optimization with a focus on parametric urbanism. The analysis addresses two research questions: \"Can parametric thinking and its associated approaches facilitate an environmental urban morphology?\" and \"If yes, can parametric urbanism support environment optimization in complex urban areas?\" Methodologies include a case study in Beijing, qualitative and quantitative analysis, parametric modeling, and environmental simulation. Results indicate that parametric techniques can effectively simulate environmental urban morphology by generating parametric models. These models provide a rational foundation for schematic decision-making about optimizing environments in urban development. Findings include a critique of parametric thinking as applied to city environments and insights about the potential uses of parametric techniques to support quality environmental urban morphology.

The present fossil fuel-based energy sector has led to significant industrial growth. On the other hand, the dependence on fossil fuels leads to adverse impact on the environment through releases of greenhouse gases. In this scenario, one possible substitute is biohydrogen, an eco-friendly energy carrier as high-energy produces. The substrates rich in organic compounds like organic waste/wastewater are very useful for improved hydrogen generation through the dark fermentation. Thus, this review article, initially, the status of biohydrogen production from organic waste and various strategies to enhance the process efficiency are concisely discussed. Then, the practical confines of biohydrogen processes are thoroughly discussed. Also, alternate routes such as multiple process integration approach by adopting biorefinery concept to increase overall process efficacy are considered to address industrial-level applications. To conclude, future perspectives besides with possible ways of transforming dark fermentation effluent to biofuels and biochemicals, which leads to circular bioeconomy, are discussed.

Integrated water planning and management face multiple challenges, among which are the competing interests of several water-using sectors and changing climatic trends. This paper presents integrated and non-integrated climate-environment-water approaches for reservoir operation, illustrated with Karkhe reservoir, Iran. Reservoir operation objectives are meeting municipal, environmental, and agricultural water demands. Results show the integrated approach, which relies on multi-objective optimization of municipal, environmental, and agricultural water supply, improves the municipal, environmental, and agricultural objectives by 70, 32, and 65% compared with the objectives\' values achieved with the non-integrated approach, which implements a standard operating policy.

Ethical issues in animal toxicity testing have led to the search for alternative methods to determine the skin sensitization potential of cosmetic products. The emergence of ethical testing issues has led to the development of many alternative methods that can reliably estimate skin sensitization potentials. However, a single alternative method may not be able to achieve high predictivity due to the complexity of the skin sensitization mechanism. Therefore, several prediction assays, including both in chemico and in vitro test methods, were investigated and integrated based on the skin sensitization adverse outcome pathway. In this study, we evaluated three different integrated approaches to predict a human skin sensitization hazard using data from in vitro assays (KeratinoSens™ and human cell line activation test [h-CLAT]), and a newly developed in chemico assay (spectrophotometric direct peptide reactivity assay [Spectro-DPRA]). When the results of the in chemico and in vitro assays were combined, the predictivity of human data increased compared with that of a single assay. The highest predictivity was obtained for the approach in which sensitization potential was determined by Spectro-DPRA followed by final determination using the result of KeratinoSens™ and h-CLAT assays (96.3% sensitivity, 87.1% specificity, 86.7% positive predictive value, 96.4% negative predictive value and 91.4% accuracy compared with human data). While further optimization is needed, we believe this integrated approach may provide useful predictive data when determining the human skin sensitization potential of chemicals.

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs.

The benefit and burden of contemporary techniques for the molecular characterization of samples is the vast amount of data generated. In the era of \"big data\", it has become imperative that we develop multi-disciplinary teams combining scientists, clinicians, and data analysts. In this review, we discuss a number of approaches developed by our University of Texas MD Anderson Lung Cancer Multidisciplinary Program to process and utilize such large datasets with the goal of identifying rational therapeutic options for biomarker-driven patient subsets. Large integrated datasets such as the The Cancer Genome Atlas (TCGA) for patient samples and the Cancer Cell Line Encyclopedia (CCLE) for tumor derived cell lines include genomic, transcriptomic, methylation, miRNA, and proteomic profiling alongside clinical data. To best use these datasets to address urgent questions such as whether we can define molecular subtypes of disease with specific therapeutic vulnerabilities, to quantify states such as epithelial-to-mesenchymal transition that are associated with resistance to treatment, or to identify potential therapeutic agents in models of cancer that are resistant to standard treatments required the development of tools for systematic, unbiased high-throughput analysis. Together, such tools, used in a multi-disciplinary environment, can be leveraged to identify novel treatments for molecularly defined subsets of cancer patients, which can be easily and rapidly translated from benchtop to bedside.

Long-term monitoring, space-for-time substitutions along gradients, and in situ temperature manipulations are common approaches to understand effects of climate change on alpine and arctic plant communities. Although general patterns emerge from studies using different approaches, there are also some inconsistencies. To provide better estimates of plant community responses to future warming across a range of environments, there have been repeated calls for integrating different approaches within single studies. Thus, to examine how different methods in climate change effect studies may ask different questions, we combined three climate warming approaches in a single study in the Hengduan Mountains of southwestern China. We monitored plant communities along an elevation gradient using the space-for-time approach, and conducted warming experiments using open top chambers (OTCs) and plant community transplantation toward warmer climates along the same gradient. Plant species richness and abundances were monitored over 5 years addressing two questions: (1) how do plant communities respond to the different climate warming approaches? (2) how can the combined approaches improve predictions of plant community responses to climate change? The general trend across all three approaches was decreased species richness with climate warming at low elevations. This suggests increased competition from immigrating lowland species, and/or from the species already growing inside the plots, as indicated by increased biomass, vegetation height or proportion of graminoids. At the coldest sites, species richness decreased in OTCs and along the gradient, but increased in the transplants, suggesting that plant communities in colder climates are more open to invasion from lowland species, with slow species loss. This was only detected in the transplants, showing that different approaches, may yield different results. Whereas OTCs may constrain immigration of new species, transplanted communities are rapidly exposed to new neighbors that can easily colonize the small plots. Thus, different approaches ask slightly different questions, in particular regarding indirect climate change effects, such as biotic interactions. To better understand both direct and indirect effects of climate change on plant communities, we need to combine approaches in future studies, and if novel interactions are of particular interest, transplants may be a better approach than OTCs.

The aim of the paper is to test the influence of social status and psychological well-being (independent variables) on hypertensive condition (dependent variable), when adjusting for traditional risk factors of cardiovascular disease (control variables). The analysis is based on data collected from SEPHAR III, a nationally representative epidemiologic study of the Romanian adult population.
Understanding the social roots of health issues is of considerable importance in developing effective strategies and policies. In this context, most studies explain the influence of social and psychological indicators on hypertension by considering the mediating effects of class-based lifestyle practices, i.e., the full range of economic, social, or symbolic resources available to particular social classes. However, the effect of traditional risk factors of cardiovascular disease in shaping the relationship between psychosocial status and hypertension has remained mostly unexplored. The influence of socioeconomic status and psychological well-being on hypertensive condition is assimilated by age as a variable with both biological and social foundations. Age appears not only as a risk factor for high blood pressure but also as an emergent component of psychosocial status. Furthermore, people without higher education are more likely to be known hypertensives with uncontrolled blood pressure values. Social and economic vulnerabilities (e.g., age, education) are interrelated with several health conditions, which support the necessity to develop and implement integrated public policies based on interventions coordinated across several domains. Moreover, social and psychological determinants that predispose to certain health risks should be considered in medical practice.

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