BioTransformations (United Kingdom)

This study explored the production of activated carbon from cocoa bean shells (CBS), both before and after solid-state fermentation, and evaluated its potential as a support for enzyme immobilization in aroma ester synthesis. Fermentation improved the physicochemical properties of the shells, increasing surface area and porosity of the resulting activated carbon. Activated carbon from fermented shells (AC-FCBS) displayed a surface area of 1158 m2/g, compared to 1050.30 m2/g for nonfermented shells (AC-CBS). These supports were tested for immobilization of Amano Lipase PS (APS), achieving relative activity yields of 72% ± 0.11 for AC-CBS, 82% ± 0.16 for AC-FCBS, and 85% ± 0.20 for the commercial resin Diaion HP-20 (DIR). In esterification reactions, APS immobilized on AC-FCBS reached 85% yield, surpassing the 75% obtained with AC-CBS. Regarding operational stability, APS-AC-FCBS retained 95% of its initial activity after five cycles and showed only a 5% reduction in conversion after seven cycles, whereas APS-DIR lost 30% under the same conditions. Notably, competitive results were achieved with lower enzyme concentrations (3 mg/g of support), highlighting the efficiency of the developed material. Overall, AC-FCBS proved to be a promising, low-cost, and effective support that enhances enzyme performance, valorizes agro-industrial residues, and contributes to sustainable esterification processes. These outcomes align with the United Nations Sustainable Development Goal 12 (Responsible Consumption and Production), promoting resource efficiency, waste reduction, recycling, and circular economy practices.

Abstract Epigenetic dysregulation is a hallmark of cancer, and tumors have evolved complex mechanisms to fine-tune oncogenic gene expression. In acute myeloid leukemia (AML), one such regulatory mechanism involves post transcriptional modification of RNAs. The most abundant post transcriptional modification is methylation of adenosine at the N6 position (m6A). This modification is catalyzed by the m6A “writer”, METTL3 and METTL14 complex, and is removed by “erasers” such as FTO and ALKBH5. m6A RNAs can regulate a variety of cellular processes which can impact tumor phenotypes, including RNA stability, splicing, and nuclear export; and METTL3 catalytic inhibitors are currently in clinical development for AML and other cancers (NCT05584111).The m6A “reader”, YTHDC1, has been recognized as a critical contributor to the proliferation and survival of AML cells. As the primary nuclear m6A reader, YTHDC1 localizes with m6A marked RNAs in phase-separated assemblies, termed biomolecular condensates, helping to maintain the stability of oncogenic transcripts such as MYC. Here, we have employed our proprietary microfluidics based screening platform (termed PhaseScanTM) to identify modulators of YTHDC1 biomolecular condensates. Evaluation of early screening hits helped identify that disruption of the interaction between YTHDC1 and m6A RNA is a functionally relevant mechanism of action (MoA) that results in dissolution of YTHDC1 condensates. Using computational and knowledge based approaches, we have identified other structurally distinct inhibitors that occupy the RNA binding pocket of YTHDC1 and disrupt its interaction with m6A RNA at nanomolar potencies. These compounds disrupt cellular YTHDC1 condensates, suppress oncogenic gene expression, and result in anti proliferative and pro-differentiation phenotypes in AML cell lines. Compounds are selective for YTHDC1 over other YTH family members and are also selective in dissolving YTHDC1 condensates over other nuclear and cytosolic condensate systems. Our optimized chemical matter has suitable ADME properties to support in vivo studies. Thus, targeting YTHDC1 biomolecular condensates represents a novel approach to the treatment of AML. Citation Format: Richard C. Centore, Mark Charles, Mansi Arora, Yiwen Chen, Matthew Watson, Charlotte Kelley, Magdalena Czekalska, Marius Rebmann, Mahmoud Ghandi, Jerome Cattin, Nagakumar Bharatham, Prathima Radhakrishnan, Alex Howarth, Gale Rudlaff, William E. Arter, Seema Qamar, Kadi Saar, Douglas Williamson, Andrew Seeber, Tuomas Knowles, Shilpi Arora. Pharmacological inhibition of the m6A RNA reader, YTHDC1, as a novel approach to targeting biomolecular condensates in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3231.

In this paper we report our kinetic study of an oxidation reaction from valencene to nootkatone using enzyme in an oscillatory baffled reactor (OBR). A full kinetic model using the Langmuir-Hinshelwood formalism was established and applied to the experimental data, allowing reactor schemes and orders to be confirmed and reaction rate constants to be extracted. The analysis of reaction rate constants suggests that most of the reversible reaction steps can be treated as irreversible, simplifying reaction schemes. The effect of mixing intensity on the kinetics was also investigated.

Silymarin is an extract from the seeds (fruits) of Silybum marianum that contains flavonolignans and flavonoids. Although it is frequently used as a hepatoprotective agent, its application remains somewhat debatable, in particular, due to the low oral bioavailability of flavonolignans. Moreover, there are claims of its potential interactions with concomitantly used drugs. This review aims at a systematic summary and critical assessment of known information on the pharmacokinetics of particular silymarin flavonolignans.There are two known major reasons for poor systemic oral bioavailability of flavonolignans: (1) rapid conjugation in intestinal cells or the liver and (2) efflux of parent flavonolignans or formed conjugates back to the lumen of the gastrointestinal tract by intestinal cells and rapid excretion by the liver into the bile. The metabolism of phase I appears to play a minor role, in contrast to extensive conjugation and indeed the unconjugated flavonolignans reach low plasma levels after common doses. Only about 1%-5% of the administered dose is eliminated by the kidneys. Many in vitro studies tested the inhibitory potential of silymarin and its components toward different enzymes and transporters involved in the absorption, metabolism, and excretion of xenobiotics. In most cases, effective concentrations are too high to be relevant under real biological conditions. Most human studies showed no silymarin-drug interactions explainable by these suggested interferences. More interactions were found in animal studies, likely due to the much higher doses administered.

In the last decade unprecedented technological changes have taken place, resulting in the emergence of a fundamentally new economic model. Based on the widespread spread of smartphones, the world has become more “connected”. The digitalization of demand and supply contributed to the creation of entirely new digital markets managed by platform enterprises based on an open business model, that enabled external consumers and producers to connect and interact with each other. A more interconnected world generates vast amounts of data, allowing platform companies to invest in machine learning and artificial intelligence and ultimately improve their efficiency. Finally, a steady digitalization of business processes, markets and global value chains is observed. In these circumstances, approaches to value addition are fundamentally changing in the context of new dimensions of the digital economy, the analysis of which was the purpose of our study. It has been identified, that in the absence of a standardized international methodology for measuring the digital economy, the latter is so far possible on disparate development-left and national statistics. Initiatives taken at the international level to overcome national differential approaches are still insufficient, as there is a lack of statistics and variables related to digital data. It has been revealed, that the lack of quality statistics on key indicators of the digital economy makes it difficult to assess the value added in the world economy scale and international comparisons. Much of the challenges of measuring value added in the digital economy, as shown in the article, are related to the principle of “scale without mass,” the intangible nature of capital, the intense growth of large-scale cross-border data flows, and the emergence of new sources of value creation.

A partir de algumas civilizações, e recorrendo a tradições conceituais diversas, este artigo é uma reflexão sobre a Educação. Recupera e resume ideias presentes em outros textos do mesmo autor sobre a participação da educação no processo de transformação social e sua relação com a democracia e com o poder. Mediante várias interrogações sobre o papel dos processos educativos em diferentes sociedades, busca-se indagar sobre as distintas práticas de educação, pensadas e vividas, seja como instrumentalização funcional de quem aprende apenas se “instruindo”, através de uma capacitação destinada a uma adaptação ao “mundo real do mercado”, seja uma educação praticada como formação integral com vistas à transformação de quem aprende através de uma inacabável partilha de saberes destinados à auto, alter e sociotransformação.

Rapeseed and its oil are the source of many biologically active substances. From crude rapeseed oil, canolol is isolated and from edible oil its dimer. Herein, we tested the biological activity of those two compounds isolated from the oils by determining their antioxidant capacity and in vitro cytotoxicity on human tumor cell lines. Canolol and its dimer showed antiproliferative activity on both cell lines with IC50 values of 46.45 μM in HeLa, and 51.19 μM in MCF7 cells, respectively. Evaluation of cell death was also done, while the oxygen radical absorbance capacity method confirmed that the canolol dimer has higher antioxidant potential than canolol. Stability of canolol and its dimer under different storage conditions showed that for a longer period of time both compounds should be stored in a freezer, but also that the dimer is more stable against degradation than canolol. Presented results indicate possible applications of canolol and its dimer in the food and pharmaceutical industry as a natural antioxidant and an anticancer agent, respectively.

Abstract Diese Arbeit zeigt, wie sich unterschiedliche Gebäude und deren unmittelbare Umgebung auf das Mikroklima in der Stadt auswirken und das Innenraumklima beeinflussen. Dafür wurden im Rahmen eines Forschungsprojektes Oberflächentemperaturen an Gebäuden, die Lufttemperaturen sowie die Luftfeuchtigkeit in Innenräumen, im Außenraum vor Fassaden und im Straßenraum gemessen. Der Niederschlag, die Sonneneinstrahlung und die Windgeschwindigkeit wurden ebenso über einen langen Zeitraum im Versuchsgebiet untersucht. Aus den Messdaten werden Auswirkungen der unterschiedlichen Gebäude auf das Innen‐ und Außenraumklima an Hitzetagen abgeleitet. Der Sockelbereich und die Fassaden der Gebäude wurden in Abhängigkeit von Farbe, Aufbau, Struktur und Dämmung analysiert. Die messtechnischen Ergebnisse dieser Arbeit bieten die Basis zur Entwicklung von Maßnahmen zur Umgestaltung und Begrünung des Straßenraumes samt angrenzenden Gebäudefassaden am Beispiel des vom UHI (Urban Heat Island)‐Effekt betroffenen Pilotgebietes Aspangstraße.