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Recent advances in the treatment of non-alcoholic fatty liver disease with astragaloside IV
No full textHUI WANG, YUNQIN JIANG, SHIYUN WANG, CHANCHAN LU, LUMIN TANG, TINGTING GU and SHU SHI
[email protected]
TCM Department, Shanghai Punan Hospital of Pudong New District, Shanghai, China
Accepted June 5, 2025
Published online June 6, 2025
Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has become a global health challenge. With the lack of effective FDA-approved treatments, alternative therapies are being explored. Astragaloside IV (AS-IV), a bioactive compound derived from the plant Astragalus membranaceus (Fisch. ex Bunge) (Fabaceae/Leguminosae), native to Inner Mongolia and Siberia, has shown significant therapeutic potential in NAFLD. This review discusses the pharmacological effects and molecular mechanisms of AS-IV, highlighting its role in improving insulin resistance, regulating lipid metabolism, reducing oxidative stress and modulating inflammation. AS-IV acts through key molecular pathways, such as AMPK, Nrf2 and SREBP-1c, to mitigate liver steatosis and inflammation. Additionally, AS-IV influences gut microbiota and bile acid metabolism, contributing to its therapeutic effects. Despite promising results from preclinical studies, clinical data supporting AS-IV's efficacy in NAFLD treatment are limited. Future research should focus on clinical trials, pharmacokinetics, and the combination of AS-IV with other therapeutic agents to optimise its therapeutic potential and reduce side effects
α-Heteroarylthiomethyl ketones: Small molecule inhibitors of 3CLproI
No full textThe main protease 3CLpro of the SARS-CoV-2 virus is a well-established therapeutic target for the treatment of COVID-19. In this study, we screened an in-house compound library and identified a series of α-heteroarylthiomethyl ketones as inhibitors of 3CLpro. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC50 values of 95.4 ± 3.1 and 95.0 ± 6.9 µmol L–1, respectively. Preliminary in vitro studies suggest a potential covalent mode of inhibition, although further studies are required to confirm this mechanism. These findings provide a new chemical scaffold for the development of 3CLpro-targeting inhibitors
Transition in Serbia: Institutions and Corruption
Get PDFThe present article deals with the transition period in Serbia in the period from 2000 to the present. Institutional reforms and the endemic occurrence of corruption at all levels are concomitant phenomena of this period. The authors try to provide answers to certain questions concerning: the causes of weak institutions in the transition period of Serbia, the possibilities of strengthening the institutions, the explanation of corrupt behavior and the lack of legislation in the supporting segments of public and economic life. The general hypothesis suggests that weak institutions and corruption are in correlative relationship: weak institutions cause greater corruption, and vice versa, stronger institutions suppress corruption. In scientific terms, this article seeks to provide answers to basic questions about the relationship of institutions and corruption, to describe the status of the studied phenomena (corruption and weak institutions) in the transition period of Serbia and to offer solutions for the problem situation. The social relevance of this study would be: identification of the problems, pointing to their harmful, and even fatal, consequences to the society and its population and, thus, contributing to the overcoming the criticality of present situation
Technology of nitrogen (N) fertilization in organic agricultural production
No full textDušik (N) je važan element za postizanje prinosa u ekološkoj poljoprivrednoj proizvodnji. Kako se u ekološkoj proizvodnji ne mogu koristiti mineralni oblici dušika, poljoprivredni proizvođači moraju se okrenuti drugim tehnologijama i koristiti nova tehnološka rješenja koja su sukladna ekološkom uzgoju. To su svakako primjena organsko-mineralnih gnojiva s višim sadržajem dušika, primjena fiksatora dušika i uzgoj leguminoznih usjeva. Time se osigurava dovoljna količina dušika za rast
lisne mase i plodova, te postizanje viših prinosa u ekološkoj poljoprivrednoj proizvodnji.Nitrogen (N) is an important element for achieving yields in organic agricultural production. Since mineral forms of nitrogen cannot be used in organic production, agricultural producers must turn to other technologies and use new technological solutions that are compatible with organic farming. These include the application of organic-mineral fertilizers with a higher nitrogen content, the application of nitrogen bacteria, and the cultivation of leguminous crops. This ensures sufficient nitrogen for the growth of leaves and fruits, and higher yields in organic agricultural production
Učinkovitost i ekološki učinak alternativnog suzbijanja korova u vinogradu
No full textIn the presented research, we tested two alternative concepts for controlling weeds under the vines as a counterweight to the glyphosate-based herbicide approach: control with plant extract-based organic fertilizer Stopeco with herbicidal action and mechanical control with the help of a combined tool consisting of rotary star tiller and finger weeder. A comparative analysis among the tested methods was done on fuel consumption, carbon footprint, grape yield, economic feasibility and environmental effect. The smallest environmental footprint was estimated for three-times application of organic fertilizer Stopeco (7.50 gha anno-1), followed by two-times glyphosate application (7.79 gha anno-1) and four times mechanical weed control (8.09 gha anno-1). However, Stopeco can be environmentally friendly from an eco-toxicological point of view. The biggest GWP emissions (990.91 kg CO2eq) and CO2 emissions (381.92 kg CO2) were again established for mechanical weeding and the smallest for glyphosate application (762.22 kg CO2eq and 351.46 kg CO2). Considering the economic
feasibility, both alternative weed control methods were comparable to the glyphosate-based herbicide because the financial benefit amounted to 1933 EUR per ha at mechanical weeding, 1085 EUR per ha at glyphosate-based herbicide, and organic fertilizer 989 EUR per ha, respectively.U ovom istraživanju testirali smo dva alternativna pristupa suzbijanju korova kod uzgoja vinove loze kao zamjenu za herbicid na bazi glifosata: suzbijanje korova organskim gnojivom Stopeco na bazi biljnih ekstrakata s herbicidnim djelovanjem te mehaničko suzbijanje pomoću kombiniranog alata koji se sastoji od rotacijske zvjezdaste freze i prstaste pljevačice. Provedena je usporedna analiza testiranih metoda u pogledu potrošnje goriva, ugljičnog otiska, prinosa grožđa, ekonomske isplativosti i utjecaja na okoliš. Najmanji ekološki učinak zabilježen je kod trostruke primjene organskog gnojiva Stopeco (7,50 gha/god), zatim kod dvostruke primjene glifosata (7,79 gha/god) i četverostrukog mehaničkog suzbijanja korova (8,09 gha/god). Međutim, Stopeco može biti ekološki prihvatljiv s ekotoksikološkog stajališta. Najveće emisije stakleničkih plinova (990,91 kg CO2eq) i emisije CO2 (381,92 kg CO2) ponovno su zabilježene kod mehaničkog uklanjanja korova, dok su najmanje emisije zabilježene kod primjene glifosata (762,22 kg CO2eq i 351,46 kg CO2). Što se tiče ekonomske isplativosti, obje alternativne metode suzbijanja korova bile su usporedive s herbicidom na bazi glifosata, s financijskom koristi od 1933 EUR po hektaru kod mehaničkog uništavanja korova, 1085 EUR po hektaru kod primjene glifosata i 989 EUR po hektaru kod primjene organskog gnojiva
Des imaginaires au-delà de l’individu. Cultures, corps et esprit au cœur de l’enseignement artistique
No full textThis paper explores the limitations of traditional approaches to art education through a biocultural lens, emphasizing the intersection of individual subjectivity and cultural influences. It critiques the conventional understanding of the aesthetic subject as autonomous, suggesting that such a view fails to account for the dynamic interaction among body, mind, and the changing world. Drawing on influential aesthetic theories and the Austrian national curriculum, the study highlights how theoretical frameworks shape educational policies and practices. Through qualitative research on “Aesthetic Practice and the Critical Faculty”, the paper exposes gaps in traditional pedagogy and proposes a phenomenologically grounded, biocultural alternative. This shift aims to offer a more holistic understanding of the aesthetic subject, enriching art education practices.Članak kroz biokulturnu leću istražuje granice tradicionalnih pristupa likovnom obrazovanju, naglašavajući sjecište individualne subjektivnosti i kulturnoga utjecaja. Kritizira konvencionalno razumijevanje estetičkog subjekta kao autonomnog i predlaže da takvo gledište ne uspijeva objasniti dinamičko međudjelovanje tijela, uma i mijenjajućega svijeta. Polazeći od utjecajnih estetičkih teorija i austrijskog nacionalnog kurikula, istraživanje ističe kako teorijski okviri oblikuju obrazovne politike i prakse. Kroz kvalitativno istraživanje »O praksi i kritičkoj moći«, članak iskazuje praznine u tradicionalnoj pedagogiji i predlaže alternativu temeljnu na fenomenologiji i biokulturnom pristupu. Ovaj pomak smjera ponuditi cjelovitije razumijevanje estetič- kog subjekta i na taj način obogatiti obrazovne prakse.Diese Arbeit untersucht die Einschränkungen traditioneller Ansätze der Kunstbildung durch ein biokulturelles Objektiv, indem sie die Schnittstelle zwischen individueller Subjektivität und kulturellen Einflüssen unterstreicht. Sie übt Kritik an der herkömmlichen Auffassung des ästhetischen Subjekts als autonom und legt dar, dass ein solcher Blickwinkel es verfehlt, die dynamische Wechselwirkung zwischen Körper, Geist und der sich wandelnden Welt zu erläutern. Unter Rückgriff auf tonangebende ästhetische Theorien und den österreichischen nationalen Lehrplan beleuchtet die Studie, wie theoretische Rahmenbedingungen der Gestaltung bildungspolitischer Maßnahmen und Praktiken ein besonderes Gepräge verleihen. Durch qualitative Forschung zu „Ästhetischer Praxis und Kritikfähigkeit“ legt das Paper die Lücken traditioneller Pädagogik offen und entwirft eine phänomenologisch untermauerte, biokulturelle Alternative. Dieser Paradigmenwechsel zielt darauf ab, das ästhetische Subjekt in einem ganzheitlicheren Verständnis zu erfassen und somit die kunstpädagogische Praxis zu veredeln.Cet article examine les limites des approches traditionnelles de l’enseignement artistique à travers une perspective bioculturelle, en mettant l’accent sur l’intersection entre la subjectivité individuelle et les influences culturelles. Il critique la conception conventionnelle du sujet esthétique comme entité autonome, en soulignant que cette vision ne tient pas compte de l’interaction dynamique entre le corps, l’esprit et un monde en perpétuel changement. En s’appuyant sur des théories esthétiques influentes ainsi que sur le programme scolaire national autrichien, l’étude montre comment les cadres théoriques façonnent les politiques et pratiques éducatives. À travers une recherche qualitative intitulée « Pratique esthétique et faculté critique », l’article met en lumière les lacunes de la pédagogie traditionnelle et propose une alternative bioculturelle fondée sur la phénoménologie. Ce changement de perspective vise à offrir une compré- hension plus holistique du sujet esthétique, enrichissant ainsi les pratiques en enseignement artistique
L’évitement de la connaissance – Cohérence, taxinomie et étiologie
No full textOften the obstacle to the advancement of knowledge is our reluctance to accept new ideas. Active ignorance thus also plays an important role in unethical behavior. Yet, despite being widely recognized as a major factor in moral misconduct across the ethical spectrum, knowledge avoidance is plagued by a lack of clarity about the precise nature and characteristics of the epistemic phenomena it encompasses. First, these phenomena appear to be contradictory, since avoidance usually requires knowledge of what is to be avoided, and thus avoidance of knowledge seems impossible. Second, knowledge avoidance seems to be an umbrella term that encompasses a variety of different doxastic states. And third, the reasons and motivations for knowledge avoidance seem to encompass biological factors as well as ontological and psychological aspects. Drawing on both traditional and contemporary philosophical literature, the present paper aims to shed light on all these faces of knowledge avoidance by exploring problems related to its consistency, taxonomy, and etiology. The essay concludes with an examination of the moral dimensions of these phenomena. It explores the problem of responsibility and culpability, and even the potential benefits of knowledge avoidance.Često je prepreka napretku znanja naša nevoljkost da prihvatimo nove ideje. Aktivna ignorantnost, stoga, također igra važnu ulogu u neetičnom ponašanju. Ipak, unatoč tome što je široko prepoznato kao glavni čimbenik moralnog prijestupa unutar čitavog spektra etičnosti, izbjegavanje znanja suočava se s nedostatkom jasnoće u pogledu točne prirode i obilježja epistemičkih pojava koje obuhvaća. Prvo, te se pojave čine kontradiktornima s obzirom na to da izbjegavanje obično zahtijeva znanje o onome što se izbjegava, pa se stoga čini da je izbjegavanje znanja nemoguće. Drugo, čini se da je izbjegavanje znanja krovni termin koji obuhvaća različita doksastička stanja. I treće, razlozi i motivacije za izbjegavanje znanja čini se da obuhvaćaju biološke čimbenike, kao i ontološke i psihološke aspekte. Oslanjajući se na tradicionalnu i suvremenu filozofsku literaturu, ovaj rad ima za cilj rasvijetliti sva ta lica izbjegavanja znanja istražujući probleme povezane s njegovom konzistencijom, taksonomijom i etiologijom. Članak stvar zaključuje ispitivanjem moralnih dimenzija tih pojava. Istražuje se problem odgovornosti i krivnje, čak i moguće koristi izbjegavanja znanja.Oftmals ist die größte Hürde für den Aufstieg des Wissens unsere Abneigung, neue Ideen anzunehmen. Aktive Ignoranz spielt daher ebenfalls eine gewichtige Rolle im unethischen Verhalten. Doch obzwar Wissensvermeidung weithin als wesentlicher Faktor für moralisches Fehlverhalten über das gesamte ethische Spektrum hinweg anerkannt ist, leidet sie unter einem Mangel an Klarheit hinsichtlich der genauen Natur und Eigenschaften der epistemischen Phänomene, die sie umgreift. Erstens scheinen diese Phänomene widersprüchlich zu sein, da Vermeidung üblicherweise Wissen über das zu Vermeidende voraussetzt – und somit erscheint die Vermeidung von Wissen als undenkbar. Zweitens scheint Wissensvermeidung ein Oberbegriff zu sein, der eine Vielzahl differenter doxastischer Zustände umschließt. Und drittens scheinen die Gründe und Motivationen für die Wissensvermeidung sowohl biologische Faktoren als auch ontologische und psychologische Aspekte zu umfassen. Gestützt auf sowohl traditionelle als auch zeitgenössische philosophische Literatur setzt sich der vorliegende Beitrag zum Ziel, Licht auf all diese Facetten der Wissensvermeidung zu werfen, indem er Problemstellungen im Zusammenhang mit deren Konsistenz, Taxonomie und Ätiologie erforscht. Der Beitrag schließt mit einer Untersuchung der moralischen Dimensionen dieser Phänomene ab. Er untersucht die Problematik von Verantwortung und Schuld und beleuchtet sogar die potenziellen Vorteile der Wissensvermeidung.Il est fréquent que l’obstacle au progrès de la connaissance réside dans notre réticence à accepter de nouvelles idées. L’ignorance active joue ainsi un rôle important dans les comportements non éthiques. Pourtant, bien que largement reconnue comme un facteur majeur de faute morale à travers le spectre éthique, l’évitement de la connaissance souffre d’un manque de clarté quant à la nature précise et aux caractéristiques des phénomènes épistémiques qu’il recouvre. Premièrement, ces phénomènes semblent contradictoires, car éviter quelque chose suppose généralement d’en avoir connaissance, rendant ainsi paradoxal l’évitement de la connaissance. Deuxièmement, l’évitement de la connaissance semble être un terme générique englobant une diversité d’états doxatiques. Troisièmement, les raisons et les motivations de cet évitement semblent inclure des facteurs biologiques, ainsi des dimensions ontologiques et psychologiques. S’appuyant sur la littérature philosophique, à la fois classique et contemporaine, cet article vise à éclairer ces différentes facettes de l’évitement de la connaissance, en abordant les problèmes liés à sa cohérence, sa taxonomie et son étiologie. Il se conclut par un examen des dimensions morales de ces phénomènes, en examinant les questions de responsabilité, de culpabilité, et même les bénéfices potentiels que pourrait comporter l’évitement de la connaissance
Post-exercise creatine kinase variability: a literature review
Get PDFCreatine kinase (CK) activity has been generally considered as reliable blood marker for assessing muscle function, damage, and repair. However, the greatest challenge in the interpretation of CK activity remains the high variability in CK increase in relation to degrees of muscle cell damage or disturbance. Several known contributors to CK variability have been identified. The most important include the type of training, exercise intensity, gender differences, body composition, intra- and interindividual biological variability, as well as preanalytical and analytical considerations. Creatine kinase variability following different types of exercise reflects the complex interplay between exercise modality, intensity, individual physiology, and recovery strategies. High-intensity exercises, especially those involving eccentric muscle contractions, tend to produce more significant CK responses due to greater muscle fiber disruption. Gender differences in CK variability are pronounced, with men generally exhibiting higher CK activities following exercise compared to women. Creatine kinase variability is also closely linked to body composition, with muscle mass generally leading to higher CK activities post-exercise, while higher body fat may correlate with lower CK responses. Regarding preanalytical and analytical considerations, perhaps the greatest challenge in CK measurement is the limited sample stability, which should always be taken into consideration when analyzing CK activity in stored samples for research or clinical purposes. This review, through exploring all of the above-mentioned sources of CK variability, could facilitate the development of evidence-based practices for preventing overuse injuries, and promoting long-term athlete health and well-being
SARS-CoV-2 structural proteins affect the expression of IL-8 and TNF-α cytokines and APOBEC genes in human lung A549 and liver Huh-7 cells
Get PDFThe apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of cytidine deaminases responsible for DNA and RNA sequence editing, playing pivotal roles in a wide range of biological processes, including immune responses, antiviral properties, and genetic mutations. In this work, we investigated the effect of SARS-CoV-2 structural proteins – Envelope (E), Spike (S), Nucleocapsid (N), Membrane (M) and protein ORF6 – on the expression of cytokines Interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α), and APOBEC3s proteins (APOBEC3B and APOBEC3F) genes in Huh-7 and A549 human cell lines. While there is plenty of scientific evidence about the effects of SARS-CoV-2 on the inflammatory cascade, the current literature regarding the impact of SARS-CoV-2 on APOBEC expression is scarce. Our findings reveal a complex relationship between SARS-CoV-2 structural proteins and the host immune response, as certain viral structural proteins (S, M, E) modulate cytokine expression, potentially contributing to the dysregulated immune responses seen in COVID-19 patients. Additionally, our research uncovered interactions between viral proteins and APOBEC genes. This study contributes to a better understanding of the host-virus interactions in the context of SARS-CoV-2 infection and provides some insights into potential therapeutic targets for mitigating the immunopathological consequences of the disease
Superposition Methods for Topology Optimization for Non-Concurrent Loads
Get PDFProblems with non-concurrent loads with variable load directions are often encountered in engineering. While dynamic topology optimization more realistically solves such problems, it is also much more computationally expensive and requires complex mathematical formulations and solvers. Hence, in this paper, we compared the performances of three superposition methods for fusing topologies obtained for various load directions. The top88 algorithm was used to generate 91 initial topologies using MATLAB, which were then joined via the superimposition method, weighted-density parameter, and the revolutionary superposition layout method. The performances of superposed topologies were then analysed by calculating their compliances for various load conditions via the finite element method also using MATLAB. The results have shown that the superimposition method and the weighted-density parameter method yield rather similar results. Both methods provided structures with lower total compliances compared to the revolutionary superposition layout method, making them more suitable for problems where stiffness is paramount