Research progress on employing medicinal plants and their active compounds to target autophagic pathways for Parkinson's disease therapy.

Host-microbial co-mediated C-sulfonation attenuates celastrol hepatotoxicity while preserving anti-rheumatic efficacy.

ABSTRACT Following the 1867 Ausgleich, Historic Hungary as part of Austria-Hungary underwent an intense era of urban modernization. This study examines how urban green spaces evolved from representative tools into organic components of the urban fabric. While theorists like Camillo Sitte and Josef Stübben provided foundational models, local experts like Antal Palóczi synthesized and adapted these concepts to address specific Hungarian urban challenges and local circumstances. Through morphological analysis and integration depth studies of Sopron and Arad, the research evaluates how late nineteenth-century regulatory plans shaped contemporary structures. Findings reveal that Sopron’s historic core maintains highly preserved urban green spaces. Conversely, in Arad, modern development has often led to the residential conversion of planned green zones, failing to fully utilize potential ecological connectivity. These historical principles remain decisive for the accessibility and spatial continuity of modern cities in the former Hungarian Kingdom.

Interest in ayahuasca and its main component, N,N-Dimethyltryptamine (DMT), has currently moved from historical and experimental use into modern clinical development. Yet, current evidence is fragmented, and systematic mapping of trial methods and design choices remains limited. We therefore systematically examined registered interventional trials of DMT, ayahuasca, and DMT combined with harmine on ClinicalTrials.gov, identifying 26 eligible trial registers for review. We extracted and harmonized trial characteristics, participant eligibility and enrollment patterns, design features, administration routes, and registered outcomes, and linked completed registrations to associated publications. The registry landscape expanded after 2020-2021 and was dominated by early-stage development, with most trials in phase I and more than half listed as completed at the time of extraction. Trials were primarily DMT-only and most often sponsored by academic or hospital institutions. Eligibility criteria were conservative, emphasizing medically and psychiatrically healthy adult cohorts and extensive cardiovascular and psychiatric exclusions. Accordingly, primary outcomes prioritized acute safety and physiological monitoring, alongside structured characterization of the subjective and altered-states profile, while disorder-specific symptom endpoints were less commonly prioritized as primary objectives. Publications linked to included trials largely reflect this early-stage focus, describing controlled administration, tolerability limits, route and formulation refinement, and initial mechanistic readouts. A smaller set of publications from depression-focused trials provides preliminary evidence of potential clinical effects, supporting further controlled replication and broader disorder-focused development. Overall, registered trials indicate an active and maturing field that has generated foundational safety and regimen knowledge, but remains constrained by a limited number of indication-specific programs beyond depression.

The modern development of the oil and gas industry is closely linked to the need to explore and develop the subsoil of regions whose geological cross-section is composed of frozen rocks. The challenges of drilling wells in frozen rocks are related to changes in their physical and mechanical state during fracture, which can lead to accidents and, if coring is necessary, to data loss. Experience shows that optimal drilling tool geometry for given conditions allows for solving a number of problems and helps maintain a certain state of certain phenomena that arise during well drilling. Therefore, the development of drilling tools for drilling in frozen rocks is a promising area and an important challenge, the solution to which will ensure favorable conditions for accessing subsoil and working in strategically important areas, such as Russia's Arctic regions. The aim of this study is to investigate the design features of drilling tools used for penetrating and sampling frozen rock and to identify geometric parameters that significantly influence the drilling process for coring wells. The following parameters were considered: the physical and mechanical state of frozen rock, the design of the drilling tool for core sampling, and the phenomena and processes occurring during drilling wells in frozen rock. The study utilized analytical methods, experimental methods, production testing, and computer modeling.The study determined that the clearance between the borehole walls and the drilling tool affects the drilling temperature regime. The optimal clearance size is shown to depend on the properties of the rock being drilled, as well as the parameters and flow rate of the cleaning agent. Key directions for developing drilling tool design methods for sampling frozen rock are identified. The best solution for sampling frozen rock formations is a thick-matrix drill bit design with a combination of PDC cutters and carbide inserts arranged in a radial staggered pattern. Various drill bit designs are proposed that improve drilling and coring conditions in frozen rock formations.

The article examines the residential architectural environment of modern Moscow. The aim of the work is to analyze decorative elements in architecture with the specifics of planning coloristic principles and their influence on the modern construction of urban complexes, which is necessary for the modern development of the city. The article examines the planning and organization of color perception of the socio-cultural space using the example of modern residential architecture in Moscow. By analyzing the architectural complexes of the modern city and its developing surroundings, a model for organizing the color space of urban developments is proposed. The article examines modern residential architectural complexes of the Russian Federation in the city of Moscow, the North-Eastern Administrative District, as well as various types of planning of decorative elements and architectural details of facades in the territories of modern urban developments. To achieve the stated goal, the work examined contemporary opinions and assessments of the planning of residential complex territories bordering historical architectural monuments and protected zones using various research methods. The obtained results make it possible to develop a model of a socially sustainable architectural ensemble that includes the functions of socio-cultural, artistic and educational significance.

The relevance of the study is due to the need to develop the theory of optimal control taking into account the level of modern development of technical systems. In scientific and applied practice, a number of new approaches to the synthesis of control systems have been formed. One of them is the N–i switching method, which attracts attention due to its algorithmic simplicity and relatively simple implementation. The generalization of the mathematical apparatus of the specified method for arbitrary order systems is based on the use of certain idealized assumptions, which lead to the limitation of the effectiveness of its use to real electromechanical control objects. Therefore, the purpose of this work is to refine the N–i switching method, aimed at increasing the performance of the relay control systems synthesized with its application. To achieve this goal, the work involved the formation of a fragment of the transition trajectory, its equivalent transformation into a rectangular diagram, the averaging of the jerk at separate time intervals, which became the basis for calculating the refined parameters of relay controllers, and a comparative analysis of the functioning of the positional electric drive control systems at various settings. Numerical experiments confirmed the improvement of the dynamic characteristics of the system. The result of the work is the expansion and refinement of the mathematical apparatus of the N–i switching method, focused on the optimization problems of third-order systems, which contributes to increasing the efficiency of control of electromechanical systems. The combination of the obtained formulas with the algorithms for the synthesis of relay systems for optimal and modal control of the electric drive is a promising implementation of the research results.

Background- Hridaya (Heart) is considered a vital organ in both Ayurveda and modern science, serving as the seat of life consciousness and circulation. Classical texts describe it as Trimarma and Sadhyapranahara Marma, highlighting its physiological and clinical significance. Objective: To elucidate the Ayurvedic and contemporary concepts of cardiac embryology with special emphasis on Hridayotpatti. Materials and Method: A qualitative, comparative review was conducted using classical Ayurvedic texts (Brihattrayi, Laghutrayi and their commentaries) and modern embryology literature. Relevant literature concepts were analyzed and correlated to identify similarities if any in cardiac development. Discussion: Ayurveda describes the origin of Hridaya as “Shonitakaphaprasadajam” formed from the essence of Shonita and Kapha along with contribution of Matruja, Pitruja and Atmaja Bhavas and Panchamahabhuta. Acharya’s state it develops early and becomes functionally active in intrauterine life. Modern embryology similarly identifies the heart as the first functional organ beginning in the third week post-fertilization from primary and secondary heart fields. The presence of cardiac jelly crucial for morphogenesis, shows resemblance to Kapha Prasada Bhaga due to its cohesive and supportive properties. Conclusion: Significant parallels exist between Ayurvedic and modern view reading early origin, functional primacy and development mechanisms of the heart.

Abstract In the flat-bottomed open ocean, the seawater density distribution yields alone the existence of geostrophic baroclinic currents and steric sea-level spatial changes. However, at basin margins, the bathymetry exerts a considerable control on both these quantities. Indeed, the steric sea level vanishes at the coast where depth is zero. Also, continental slopes are vorticity barriers hindering convergence (divergence) of baroclinic transport toward the coast and accumulation (removal) of water there. In the limit of no temporal development, how the coastal sea level is impacted by open-ocean density changes is hence nontrivial and must involve ageostrophic mechanisms. Here, we focus on bottom friction as one such process, provide derivations extending the arrested topographic wave theories to a fully baroclinic ocean, and discuss an application for an eastern boundary margin (representative of the Rockall Slope Current region, for example). We demonstrate that open-ocean density changes yield important joint effect of baroclinicity and relief (JEBAR) along-slope currents, which generate cross-slope Ekman currents due to friction with the seabed. The latter are associated with divergence and convergence leading to sea-level changes above the slope, mediated to the coast via coastally trapped waves. Through this process, not only the coastal sea level is modified but also the along-slope currents are slowed down to well-known asymptotical solutions. Hence, our results link modern theoretical developments in sea-level research and past analytical studies of slope currents. Our effort describes the fundamental notions, and we anticipate it paves the way for more sophisticated works.

The acquisition and long-term retention of new vocabulary are frequently impeded by traditional, passive learning methods like rote memorization, which fail to address the cognitive principles of memory and contextual understanding. This project, the Smart Vocabulary Builder, presents a full-stack, AI-powered web application designed to overcome these challenges by creating a highly efficient, personalized, and interactive learning environment. The system is architected with a robust Python-based FastAPI backend, a dynamic React.js frontend, and leverages a database managed by SQLAlchemy. At its core, the application implements a Spaced Repetition System (SRS), utilizing a priority queue to intelligently schedule word reviews at optimal intervals, thus combating the natural forgetting curve. Innovation within the project is driven by the deep integration of the Google Gemini API, which transforms the learning process into a conversational experience. When a user adds a new word, the application initiates an "AI Consultation," providing not just a definition, but also a contextual example sentence and a creative mnemonic. This interaction is dynamic, allowing users to regenerate explanations if clarity is not achieved. The platform further personalizes the learning journey by proactively suggesting new, relevant words based on the user's existing vocabulary. A key feature is the integrated, browser-native "Listen & Practice" tool, which combines text-to-speech and speechto-text functionalities for pronunciation feedback without reliance on costly external services. The result is a feature-complete, intelligent learning platform that successfully merges fundamental computer science algorithms, modern full-stack development practices, and the power of generative AI to offer a demonstrably more effective and engaging alternative to conventional vocabulary-building methods.

This study examines the application of humanistic psychology in modern Islamic education, departing from the issue that educational practices remain predominantly mechanistic and deterministic, thereby providing limited space for freedom, meaning, and the optimal development of students’ innate potential (fitrah). This condition calls for an alternative approach that is more oriented toward learners as active subjects in the educational process. The objective of this study is to elaborate on the development of humanistic psychology, starting from its philosophical roots, the classical phase (the ideas of Maslow and Rogers), to its contemporary phase (positive psychology, third-wave CBT, and neuroscience), as well as to formulate its practical implications for designing Islamic education that is relevant to current needs. The subject of this research consists of key literature on humanistic psychology, existentialism, phenomenology, and various contemporary writings in the field of Islamic education. The findings indicate a strong alignment between humanistic principles and the fundamental concepts of Islamic education, such as human dignity, fitrah, responsible freedom, and holistic character development. Classical humanism emphasizes empathetic and learner-centered educational relationships, while modern developments provide an empirical foundation for examining well-being, self-awareness, and character strengthening. It is concluded that integrating humanistic psychology with Islamic values has the potential to produce a more humanistic, dialogical, contextual, and transformative model of Islamic education.

This study aims to examine the application of an expository approach in the scriptwriting of the documentary film "Jejak Rasa," which highlights Southern Chinese cuisine in Bandung as a representation of cultural acculturation. The background of this research is based on the declining interest of the younger generation in traditional culinary arts due to the influence of globalization and social media trends. The methods used included literature research, field observations, and interviews with relevant sources, such as culinary entrepreneurs and museum officials. The results show that the expository approach is effective in conveying information systematically, factually, and easily understood through the use of voice-over narration as the main direction of the story. Furthermore, the use of an implied first-person perspective creates an emotional connection between the audience and the material presented. This documentary serves not only as an information medium but also as a means of education and preservation of Peranakan Chinese culinary culture. By combining visual elements, narrative, and interviews, this documentary comprehensively presents historical, social, and cultural values. Therefore, this work is expected to raise public awareness of the importance of preserving culinary cultural heritage amidst modern developments.

The digital economy is one of the central trends of modern global development. In addition, the small and medium-sized business segment is one of the main pillars of the economy. Digital transformation of businesses requires the integration of new business models, digital technologies and innovative solutions. State support plays a crucial role in this process, especially for small and medium-sized businesses, which often do not have sufficient financial or human resources for digital transformation. Various state programs implemented in Georgia aim to strengthen the digital skills of small businesses and develop the technological ecosystem. However, it is important to assess how effective these programs are in practice — how they affect business productivity, employment, regional development and the overall growth of the digital economy. The aim of the study is to assess the effectiveness of state support programs for digital small and medium-sized businesses in Georgia in the context of economic development. The objectives of the study are: to examine the structure and goals of the main programs implemented by the state; To analyze the impact of these programs on the digital level of business, employment and innovative activity; to identify problematic aspects of the effectiveness of the programs; to develop recommendations for improving state policy. The study is based on a mixed approach - a combination of quantitative and qualitative analysis. The study shows that Georgia's digital support programs actually contribute to the growth of small and medium-sized businesses, especially in urban environments. However, limitations in effectiveness are visible in various areas, including access to financing, digital skills shortage, lack of long-term monitoring, etc. The study showed that the programs contributed to the formation of a startup ecosystem, the development of digital services and employment growth, however, maximizing their effectiveness requires the implementation of structural reforms.

This article analyzes Indigenous peoples’ negotiations in the implementation of the Sustainable Development Goals through a comparative study of the Malaumkarta communities in Indonesia and the Bonda communities in India. Integrating Gramsci and Spivak’s subaltern theories with Escobar’s political ecology, this study identifies five dimensions of negotiation: everyday resistance, strategic adaptation, lawfare, maintenance of traditional practices, and multi-scale negotiation. Malaumkarta adopts formal engagement through the Sasi system and the Customary Council, while Bonda employs strategic isolation through traditional millet farming. The findings demonstrate that Indigenous peoples’ environmental struggles are ontological struggles that articulate the pluriversity of knowledge, challenging the hegemony of modern development discourse. This article calls for decolonizing the Sustainable Development Goals toward a platform that recognizes Indigenous knowledge as an equal epistemology.

Examines the main approaches to chemical, physical, and composite modification of polyethylene, including functionalization, the creation of nanocomposites, and the use of biofillers. Modern PE waste recycling technologies are analyzed, including mechanical recycling, thermal processing (pyrolysis), and promising methods of chemical depolymerization. It is shown that integrating modification and rational recycling not only improves the material's properties but also reduces its environmental footprint. Directions for further research aimed at improving the quality of recycled polyethylene and expanding its applications are proposed.

The increasing adoption of Large Language Models (LLMs) has created a critical need for high-quality, structured training data derived from real-world, unstructured sources such as documents and web content. However, existing research primarily focuses on model architectures or isolated data processing stages, lacking a unified solution for end-to-end dataset preparation. This project proposes a reusable, production-ready Dataset Preparation Pipeline that automates the ingestion, cleaning, chunking, task-specific data generation, and quality evaluation of raw data for multiple LLM applications including question answering, summarization, and classification. The system integrates automated quality assessment to filter low-quality or biased samples and exports curated datasets in standard formats for seamless downstream use. By adopting a data-centric approach, the proposed pipeline bridges the gap between raw real-world data and reliable LLM training datasets, enabling scalable, continuous, and efficient dataset generation for modern language model development.

The FDA's Project Optimus initiative emphasizes dose optimization through randomized cohorts and comprehensive evaluation across dose levels. Additionally, early-phase oncology trials must efficiently evaluate antitumor activity while maintaining patient safety, requiring robust statistical frameworks for futility monitoring. We propose a seamless two-stage Phase I/II trial design integrating dose optimization with efficacy evaluation. Stage 1 employs a dose-finding approach with patient backfilling, utilizing Bayesian optimal boundaries for efficacy and toxicity to select two promising doses for further evaluation. The backfill strategy enables sequential enrollment while previous patients continue their evaluation periods, thereby accelerating the trial. Stage 2 simultaneously identifies the optimal dose and evaluates treatment effectiveness through joint monitoring of efficacy and toxicity outcomes. Stage 2 incorporates Bayesian optimal boundaries for both futility and efficacy stopping, enabling early decision-making while explicitly controlling Type I error rates. Simulation studies across realistic scenarios demonstrate superior operating characteristics of the proposed design compared to existing designs, making this approach particularly valuable for modern oncology drug development where efficiency, accuracy, and patient safety are paramount.

Introduction: The diagnosis, treatment, and prevention of neurodegenerative conditions and dementia remain highly important. One of the most common anatomical manifestations of the conditions accompanied by cognitive impairment is ventriculomegaly, which is assessed using ventricular-cranial coefficients. The modern development of information technologies allows estimating the distribution of coefficient values across the general population and clarifying the normal values of these coefficients for patients of different age groups, depending on their gender. Objective: Тhe study was to use modern AI technologies to evaluate generally accepted indicators of ventriculomegaly in the population as risk factors for various neurodegenerative processes and to determine the normal values of ventricular-cranial coefficients depending on the gender and age of the study subjects. Materials and methods : A retrospective descriptive epidemiological study was conducted in Moscow for a period of one calendar year — from February 2024 to February 2025. The results of brain CT scans of 121,973 subjects were analyzed, of which 59,079 (48.4%) were men and 62,885 (51.6%) were women. The analysis included the assessment of such indicators as VCR1, VCR2, VCR3, and the width of the third ventricle of the brain and was performed in an automated mode. Statistics: Data were summarized using descriptive statistics, including the number of non-missing values (N), minimum (Min), maximum (Max), arithmetic mean (M), standard deviation (SD), 95% confidence interval (CI) for the mean, median (Me), and first and third quartiles (Q1, Q3). Analysis of variance (ANOVA) was employed to compare numerical variables. Regression analysis was performed to identify factors significantly correlating with fluctuations in coefficients. Results: With age, the median of VCR1 increases from 25.0% to 31.0% in the mixed group (men and women), VCR2 from 9.0% to 17.0%, VCR3 from 4.0% to 9.0%, and the width of the third ventricle from 5 mm to 11 mm. An increase in age by one year has a significant impact on the change in these indices in all groups, e.g., the VCR1 increases by 0.15 units for each year of increase in the subject’s age. The dynamics of the VCR1, VCR2, and VCR3 are identical for men and women. The width of the third ventricle in men increases by 10% more than in the female group. According to the regression analysis data, all four assessed indicators are significantly higher on average in men than in women of the same age (p<0.001, confidence intervals: VCR1 – 1.63, 2.0; VCR2 – 1.3, 1.78; VCR3 – 0.41; 1.33; the third ventricle width – 0.95, 1.16). The average VCR1 values in the group of centenarians are more than 0.3 for both sexes. Discussion: The observed morphometric parameters exhibited population-level variability; however, as we achieved sufficient sample size, our analysis revealed that sexual dimorphism and deviations from normal values significantly correlate with patient age. Reference values for the evaluated morphometric coefficients cannot be identical across sex and age groups. In healthy cohorts, these coefficients are inherently higher in elderly individuals than in younger populations, with males exhibiting higher values than females within the same age group. Deviations from the reference values are critical, particularly among elderly patients and more specifically within the male demographic. Conclusion: The value of VCR1, VCR2, VCR3, and the width of the third ventricle are statistically significantly higher in men of all age groups than in women of the same age group. With age, the value of VCR1, VCR2, and VCR3 increases synchronously in both sexes, and the width of the third ventricle in men increases at an accelerated rate compared to women (the difference is approximately 10%). New refined normal values of ventricular-cranial coefficients for different age groups of the Russian population depending on gender are proposed.

This study aims to examine and analyze the changes in the expanded meaning of netizens' comments on Fiersa Besari's Instagram account (@fiersabesari). This research method uses a qualitative descriptive method. The results of the study indicate that the expansion of expanded mea ning occurs in netizens' comments on the Indonesian artist's Instagram social media account. This expansion of meaning most likely occurs as a result of increasingly rapid technological and modern developments. Netizens as language users are also influenced by the conditions that occur around them. In addition, changes in expanded meaning also show that language is static and not dynamic. There are several characteristics that language has, namely language can live and continue to develop if the language is continuously used by its users and language can change its meaning according to the wishes of its users. In other words, there are no boundaries in language, which means language is able to develop and change according to the needs of its users. This phenomenon of changing meaning is also a concrete example that language does experience development and language is arbitrary.

Community service is part of the implementation of the Tri Dharma of Higher Education, which is directed at improving the quality of education through empowering students according to the needs of modern learning developments. Through community service activities, universities not only play a role in the development of science but also make a real contribution in addressing practical needs in the educational environment. This community service activity aims to improve the ability of elementary school students in using interactive digital media to support more effective learning in the classroom. The activity was carried out from February to March 2026, involving 40 students as the main participants. The implementation method used a participatory approach and drill and practice through four training sessions: an introduction to interactive projectors and screens, presentation training using Microsoft PowerPoint, visual design practice using Canva, and presentation of student work. The results of the activity showed that students were able to understand the basic functions of digital media, create simple presentations, and present their work in front of the class with more confidence. The use of digital media also helps create more structured learning, increases student participation, and facilitates understanding of the material through visual presentations. This program demonstrates that simple digital media training can be an effective first step in supporting technology-based active learning in elementary schools.