21st Century Research Articles

Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review).

Cancer is a significant societal, public health and economic challenge in the 21st century, and is the primary cause of death from disease globally. Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) serves a crucial role in several biochemical processes, including adenosine triphosphate hydrolysis, purine metabolism and regulation of signaling pathways. Specifically, ENPP1, a type II transmembrane glycoprotein and key member of the ENPP family, may be upregulated in tumor cells and implicated in the pathogenesis of multiple human cancers. The present review provides an overview of the structural, pathological and physiological roles of ENPP1 and discusses the potential mechanisms of ENPP1 in the development of cancers such as breast, colon, gallbladder, liver and lung cancers, and also summarizes the four major signaling pathways in tumors. Furthermore, the present review demonstrates that ENPP1 serves a crucial role in cell migration, proliferation and invasion, and that corresponding inhibitors have been developed and associated with clinical characterization.

PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.

In the realm of oncology, the transformative impact of PROTAC (PROteolysis TAgeting Chimeras) technology has been particularly pronounced since its introduction in the 21st century. Initially conceived for cancer treatment, PROTACs have evolved beyond their primary scope, attracting increasing interest in addressing a diverse array of medical conditions. This expanded focus includes not only oncological disorders but also viral infections, bacterial ailments, immune dysregulation, neurodegenerative conditions, and metabolic disorders. This comprehensive review explores the broadening landscape of PROTAC application, highlighting ongoing developments and innovations aimed at deploying these molecules across a spectrum of diseases. Careful consideration of the design challenges associated with PROTACs reveals that, when appropriately addressed, these compounds present significant advantages over traditional therapeutic approaches, positioning them as promising alternatives. To evaluate the efficacy of PROTAC molecules, a diverse array of assays is employed, ranging from High-Throughput Imaging (HTI) assays to Cell Painting assays, CRBN engagement assays, Fluorescence Polarization assays, amplified luminescent proximity homogeneous assays, Timeresolved fluorescence energy transfer assays, and Isothermal Titration Calorimetry assays. These assessments collectively contribute to a nuanced understanding of PROTAC performance. Looking ahead, the trajectory of PROTAC technology suggests its potential recognition as a versatile therapeutic strategy for an expansive range of medical conditions. Ongoing progress in this field sets the stage for PROTACs to emerge as valuable tools in the multifaceted landscape of medical treatments.

Talent Development in Inclusive Classrooms: An Analysis of Student Growth

In this 21st century context, communities and nations cannot afford to lose the talents of any young people. Shifts in thinking and practices are needed: from one-dimensional definitions to varied talents and 21st century skills of creativity, critical thinking, collaboration, and communication; from identification to assessment; from the goal of eminence to wisdom; from special programs to services in inclusive settings. To substantiate these changes, we analyzed student growth in creative problem solving in mathematics and science, and knowledge structure in an Australian school. Significant gains were made by all students at all levels of performance on three assessments, showing that all students in inclusive classrooms benefitted from the implementation of Maker's (1982) talent development principles. Implementing a teaching model such as Real Engagement in Active Problem Solving (REAPS) and assessment of creative problem solving are recommended. Instruments with no ceilings are needed, especially for assessing growth of high ability learners.

Epidemiology and geographical patterns of common childhood cancers in Iran: Evidence from the National Cancer Registry

IntroductionCancer is projected to become the primary cause of death in the 21st century. Although childhood cancer is relatively rare, it remains a significant contributor to mortality among children. This study examines the geographical distribution of childhood cancer incidence in Iranian provinces using data from the National Cancer Registry between 2014 and 2018. Materials and methodsThis registry-based study analyzed data from 14,711 children under 20 diagnosed with common childhood cancers, sourced from the Iranian National Population-based Cancer Registry for the period 2014–2018. The age-standardized incidence rates (ASR) were calculated using direct standardization methods and reported per 1 million person-years. Spatial autocorrelation measures, including global and local indices such as Moran's I and Getis-Ord's G, were employed to identify high-risk and low-risk areas, assess overall spatial dependence, and pinpoint specific clusters and hotspots of incidence rates. ResultsASR for childhood cancer in Iran was 119.56 per 1 million individuals aged 0–19 years. Boys had a higher ASR (129.98) than girls (107.68). Childhood cancer cases increased from 2765 in 2014 to 3354 in 2018, with leukemia as the most common type, followed by brain and nervous system, lymphoma, bone, and connective and soft tissue cancers. Spatial analysis identified high-risk clusters in central Iran (Isfahan, Yazd, Tehran) and low-risk clusters in the northeast (Kermanshah, West and East Azerbaijan, Kurdistan). ConclusionThis study highlights high childhood cancer incidence in Iran, particularly among boys and in central regions, with elevated leukemia rates. These findings call for targeted prevention strategies and further research to address geographic and gender disparities and to improve care programs.

Revolutionizing Antiviral Therapeutics: In silico Approaches for Emerging and Neglected RNA Viruses.

The 21st century has shown us how rapidly the pandemic can evolve and devastate the life of human beings without differentiating between the continents. Even after the global investment of billions of dollars into the healthcare sector, we are still lacking multiple therapeutics against emerging viruses. World Health Organization (WHO) has listed a number of viruses that could take the form of pandemics at anytime, depending upon their mutations. Among those listed, the SARS-CoV, Ebola, Zika, Nipah, and Chikungunya virus (CHIKV) are the most known viruses in terms of their number of outbreaks. The common feature among these viruses is their RNA-based genome. Developing a new therapeutic candidate for these RNA viruses in a short period of time is challenging. In silico drug designing techniques offer a simple solution to these problems by implementing supercomputers and complicated algorithms that can evaluate the inhibition activity of proposed synthetic compounds without actually doing the bioassays. A vast collection of protein crystal structures and the data on binding affinity are useful tools in this process. Taking this into account, we have summarized the in silico based therapeutic advances against SARS-CoV, Ebola, Zika, Nipah, and CHIKV viruses by encapsulating state-of-art research articles into different sections. Specifically, we have shown that computer- aided drug design (CADD) derived synthetic molecules are the pillars of upcoming therapeutic strategies against emerging and neglected viruses.

Bio-morphological traits, chemical composition, and antioxidant activity of two accessions from sainfoin seeds

The importance of some underutilized legume crops in creating sustainable bioeconomy is increasing constantly in the 21st century. Apart from the commonly used beans, the most of them are mainly utilized as animal forages. Such crop is sainfoin which has the ability to resist droughts and adapt to a wide range of climatic conditions. Hence, it is substantial to be performed detailed studies on the genetic diversity of the plant as well as to be established the main components derived from the sainfoin seeds. Therefore, the aim of the present study was the examination of the variability of some important bio-morphological traits of two sainfoin accessions – Onobrychis transcaucasica Grossh. and Onobrychis viciifolia Scop., as well as revealing the chemical composition and antioxidant activity of the seeds. The highest variability for both species was the trait top leaflet width. The amount of glyceride oil, total proteins, carbohydrates (water-soluble sugars, starch and fibers), ash and moisture of the seeds were determined. Total phenolics and flavonoids, as well as their individual content in the sainfoin seeds revealed them as a potent source of bioactive components. The antioxidant activity was examined using four methods based on different mechanisms (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant ability (FRAP) and cupric reducing antioxidant capacity (CUPRAC)). The results of this study have possibilities for enrichment the information on ex situ collection of O. transcaucasica and O. viciifolia accessions. They could be successfully used in the improvement of breeding programs and the seeds might have possible application for different industrial purposes because of their chemical composition.

Land reform catalysts of capitalism and communism: 150 years of agricultural change in Romania

This paper presents a comprehensive overview of historical Romanian agricultural changes from the nineteenth to the twenty-first centuries, focusing on the main land reforms and their effects on land ownership patterns, spatial disparities and their consequences on individual farms. The study follows a stepwise chronological approach covering these major historical periods: modern Romania before the First World War; Romania in the interwar period and during the Second World War; Communist Romania; and Post-communist Romania. Four major land reforms took place in Romania (in 1864, 1921, 1945 and 1991) within distinct political, economic and social historical contexts. One of the aims of these land reforms was to increase the individual rights of peasants, typically associated with the creation of individual households in agricultural economies. Moreover, this study provides a geographical examination of how the land reforms acted as a catalyst for the transition from capitalism to communism, and later, back to capitalism.

Using mercury and lead stable isotopes to assess mercury, lead, and trace metal source contributions to Great Salt Lake, Utah, USA

Great Salt Lake is a critical habitat for migratory birds that is threatened by elevated metal concentrations, including mercury (Hg) and lead (Pb), and is subject to severe hydrologic changes, such as declining lake level. When assessing metal profiles recorded in Great Salt Lake sediment, a large data gap exists regarding the sources of metals within the system, which is complicated by various source inputs to the lake and complex biogeochemistry. Here, we leverage Hg and Pb stable isotopes to track relative changes in metal source contributions to Great Salt Lake over time. Mercury and Pb concentrations increase in sediments deposited after 1920 and peak between 1965 and 1995, following closure of several local smelters and the onset of increased emission controls. The nominal associations above are confirmed via Hg stable isotopes in pre-1920 background sediments, which reflect atmospheric inputs from regional and global origin, whereas Hg and Pb stable isotopes together indicate that elevated metal concentrations in mid-late 20th century sediments reflect increased mining/smelting inputs. The observed minimal rebound towards pre-1920 Pb isotope signatures in 21st century sediments indicates that mining/smelting inputs, though reduced, remain a primary source of Pb to Great Salt Lake. In contrast, the more pronounced rebound of Hg stable isotope signatures to pre-1920 values indicate a greater contribution of atmospheric inputs of regional/global origin to current Hg inputs, though Hg concentrations are ~10 times greater than pre-1920 background values due to global increases in atmospheric Hg concentrations or possibly slow recovery from local contamination. The importance of regional/global Hg sources to the system suggests that reductions in Hg bioaccumulation in the open water food webs of Great Salt Lake are more dependent on national and global reductions in Hg emissions and management strategies to limit methylmercury production within system. This work highlights the utility of using coupled Hg and Pb stable isotope values to assess trace metal pollution sources and pathways in aquatic systems.

Effects of Consuming Repeatedly Heated Edible Oils on Cardiovascular Diseases: A Narrative Review.

Edible oils are inevitable requisites in the human diet as they are enriched with essential fatty acids, vitamins, carotenoids, sterols, and other antioxidants. Due to their nutritive value and commercial significance, edible oils have been used for food preparation for many centuries. The use of global consumption of edible oils has dramatically increased throughout the world in the 21st century owing to their incredible application in all kinds of food preparation. However, a variety of pollutants, such as pesticides, toxic chemicals, heavy metals, and environmental pollution, have contributed to the contamination of edible oils. Furthermore, the benzophenanthridine alkaloids, sanguinarine, dihydrosanguinarine, butter yellow, and other several agents are added intentionally, which are known to cause a number of human diseases. Apart from this, repeated heating and reusing of oils results in trans fats, and lipid peroxidation alters the fatty acid composition, which adversely affects the health of consumers and increases the risk of cardiovascular diseases. Moreover, the prevention of edible oil contamination in human health at various levels is inevitable to ensure consumer safety. Hence, the present review provides an overview of vegetable cooking oils and the health ailments that detection techniques are focused on.

A Review on Innovative Nanomaterials for Enhancing Energy Performance of the Building Envelope

Abstract: The greatest threat of the 21st century is global warming. The building sector is a major contributor to energy consumption and greenhouse gas emissions. About 60% of the total energy consumed in the buildings is caused by HVAC systems. Nanotechnology is an emerging technology that can introduce innovative materials in the building sector which offers great potential for development of innovative building products to enhance performance and energy efficiency of the building. Nanomaterials are a promising candidate for building thermal insulation. This paper presents a theoretical overview of twenty case-based scenarios on the application of nanomaterials to reduce energy consumption in buildings. A comprehensive list of different nanomaterials is reviewed from the literature, as non-structural, insulation, and thermal energy storage materials to improve the insulation performance of the building. Extensive testing and simulation modelling have turned out to be the most popular in this area of research methods for experimental and theoretical studies. The combination of these methods can yield a reliable technique for studying nanomaterials. Finally, embedding nanomaterials into building walls, floors, and roofs can reduce energy consumption and enhance thermal performance of a building’s envelope.

Responses of vegetation low-growth to Extreme Climate Events on the Mongolian Plateau

Since the 21st century began, the frequency and intensity of extreme climate events have significantly increased globally, becoming a widely recognized phenomenon of global change. These extreme events, including droughts and heatwaves, have profound impacts on the structure and function of ecosystems. This study focuses on the Mongolian Plateau. It utilizes meteorological and remote sensing vegetation data, combined with consistency and sensitivity analyses. These approaches aim to provide an in-depth understanding of the relationship between various extreme climate events and vegetation low-growth. The study found that extreme drought and extreme heat events are the primary drivers affecting vegetation low-growth on the Mongolian Plateau. The analysis results indicate that the sensitivity of vegetation to these extreme climate events is regulated by regional hydrothermal conditions, with vegetation in long-term drought areas being more susceptible to the suppression of extreme drought, while humid areas exhibit some resistance. As the temperature gradient increases, the sensitivity of vegetation to extreme high temperatures increases, while sensitivity to extreme low temperatures decreases. Furthermore, the study also revealed differences in the responses of different vegetation types to extreme events under the same climatic conditions, highlighting the ecological basis of ecosystem resilience and adaptability. This research not only enhances our understanding of vegetation dynamics under the influence of extreme climate events but also provides scientific evidence for ecological management and climate adaptation in the Mongolian Plateau region.

Nano - Based Therapeutic Strategies in Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, progressively distinctive via cartilage destruction, auto-antibody production, severe joint pain, and synovial inflammation. Nanotechnology represents as one of the utmost promising scientific technologies of the 21st century. It exhibits remarkable potential in the field of medicine, including imaging techniques and diagnostic tools, drug delivery systems and providing advances in treatment of several diseases with nanosized structures (less than 100 nm). Conventional drugs as a cornerstone of RA management including disease-modifying antirheumatic drugs (DMARDS), Glucocorticosteroids, etc are under clinical practice. Nevertheless, their low solubility profile, poor pharmacokinetics behaviour, and non-targeted distribution not only hamper their effectiveness, but also give rise to severe adverse effects which leads to the need for the emergence of nanoscale drug delivery systems. Several types of nano-diagnostic agents and nanocarriers have been identified; including polymeric nanoparticles (NPs), liposomes, nanogels, metallic NPs, nanofibres, carbon nanotubes, nano fullerene etc. Various patents and clinical trial data have been reported in relevance to RA treatment. Nanocarriers, unlike standard medications, encapsulate molecules with high drug loading efficacy and avoid drug leakage and burst release before reaching the inflamed sites. Because of its enhanced targeting specificity with the ability to solubilise hydrophobic drugs, it acts as an enhanced drug delivery system. This study explores nanoparticles potential role in RA as a carrier for site-specific delivery and its promising strategies to overcome the drawbacks. Hence, it concludes that nanomedicine is advantageous compared with conventional therapy to enhanced futuristic approach.

How could 50 °C be reached in Paris: Analyzing the CMIP6 ensemble to design storylines for adaptation

Reaching a surface temperature of 50 °C in a heavily populated region, like Paris, would have devastating effects. Although such a high value seems far from the present-day record of 42.6 °C, its occurrence cannot be dismissed by the end of the 21st century, due to the continuous increase of global mean temperature. In this paper, we address two questions that were asked by the City of Paris to a group of scientists: When does this event start to be likely? What are the prevailing meteorological conditions? We base our study on the CMIP6 simulation ensemble. Many of the CMIP6 yield biases in temperature. Rather than using methods of bias correction, which are not necessarily adapted to high extremes, we propose a pragmatic approach of model selection in order to seek such high temperature events that are deemed realistic. We analyze the meteorological conditions leading to first occurrences of such hot events and their common atmospheric patterns. This paper describes a simple data mining approach (on a large ensemble of climate model simulations) which could be adapted to other regions of the world, in order to help decision makers anticipating and adapting to such devastating meteorological events.

A Comprehensive review on COVID-19: From clinical characterizations to treatment

In December 2019, the outbreak of COVID-19 started which was originally believed to be pneumonia. Later on, after studies of vaccination and sign, symptoms revealed it to be a SAR-CoV (severe acute respiratory syndrome coronavirus 2), results in infection of the lower respiratory areas that centrals to risky breath shortness and even death. This pandemic not only brought massive human lives but also economic as well as societal loss, rising death numbers in millions, 21st century’s deadliest viral disease till now. The world economic forum supported and appreciated each step for the treatment of COVID 19. Leading supporters to work immensely for the vaccine’s formulation. Though, being an RNA virus, it deploys its genetics speedily and makes it hard almost impossible for the next mutated strain to be targeted by the same vaccine. Structurally it is like crown with spikes on it, that gets attached to the host cell. COVID-19 identified in the year 2019 but documented in February 2020, by the World Health Organization.

Past, Present and Future of Phase 3 Vaccine Trial Design: Rethinking Statistics for the 21st Century.

Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomised controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.

Can 21st century women have the best of both worlds? Reality or dream?

PurposeThis study explored whether women could “have it all,” both at home and in the workplace. Using neoliberal feminism, mental load theory and intergenerational perspective as theoretical frameworks, this study explored how neoliberal ideologies which emphasized individual agency, economic empowerment and self-responsibility interact with persistent gendered expectations/norms to influence women’s experiences in navigating familial commitments and career aspirations.Design/methodology/approachAround 140 (N = 140) women living in Australia were recruited to participate in a qualitative, open-ended questionnaire that aimed to explore their: (1) perceptions and (2) expectations about (a) how gender roles evolved for them from youth to adulthood in various contexts, (b) how their family structures and dynamics, such as attitudes toward marriage, caregiving and/or household responsibilities, have changed and (c) what has/have influenced their career aspirations and family choices.FindingsResults revealed a trend of women who worked hard at home and professionally. Unlike women who in the past lived more traditional lives, women in our cohort focused on their career as an important part of their identity and self-fulfillment. However, many women did report heightened mental load, stress and a lack of physical exercise in their daily lives.Originality/valueThis study revealed complex interplay between societal norms, intergenerational influences and the cognitive burdens associated with managing multiple roles. By examining these dynamics and using an integrated theoretical framework, the article aimed to holistically explain the challenges women in Australia encounter as they try to balance familial obligations with career ambitions within changing socioeconomic contexts.

Collective Land Rights and Capitalist Economy, 19th–21st Centuries

Collective Land Rights and Capitalist Economy, 19th–21st Centuries

Prostitution in Bulgaria during the 19th, 20th and 21st Centuries – from Economic Activity to Social Parasitism

Prostitution in Bulgaria during the 19th, 20th and 21st Centuries – from Economic Activity to Social Parasitism

The perceptions of secondary school students regarding the learning of computer programming at Key Stage 4 in the revised curriculum in England: problems and solutions.

Programming is becoming progressively important for many societies in the world today. It is also required in educational institutions and is especially important for students who will be graduating and looking for employment opportunities in the future. However, the teaching of a programming is not well developed in many secondary schools in different areas in England. Today, teaching programming is considered to be of the priority domain of several countries in the twenty-first century. Interest in this domain is wide and the amount of research conducted in the field is numerous. This study was designed to investigate and to aid a critical students’ understanding of the learning of programming in the revised Key Stage 4 (KS4) Computer Science (CS) curriculum. It seeks to understand the impact of learning programming on student’s perceptions toward programming and how to improve the teaching and learning of programming. The study found that the issues faced by students learning programming include a lack of time, the perception that it is a ‘difficult’ subject and students’ insufficient understanding of programming. The findings also suggest that schools have made efforts to overcome these challenges and are willing to adopt programming as a subject and to help, encourage, develop and improve students’ ability to learn programming.

The Fifth Generation of Revolution Studies. Part I: When, Why, and How Did It Emerge

There are grounds for claiming that a new (‘fifth’) generation of revolution studies has emerged in the 21st century. It can be noted that the characteristics of this generation are as follows: a tendency toward a macro-level outlook, encompassing both historical and geographical dimensions, coupled with a propensity toward a systemic approach; study of distinct types of revolutionary processes, such as Mark Beissinger’s ‘urban civic revolutions’, and the pivotal revolutionary innovations, including the impact of new information technologies in recent revolutions; innovations regarding the factors and causes of revolutions and innovations in the analysis of the factors influencing the choice of revolutionary strategy and revolution outcomes; a special interest in the topic of revolutionary waves/‘the diffusion of revolution’; a strong understanding that armed and unarmed revolutionary events are characterized by significantly different factors, structure, and consequences; a focus on the study of unarmed revolutionary episodes/‘non-violent maximalist campaigns’; the use of global databases of revolutionary events; extensive use of modern methods of quantitative analysis.