RESUMEN
Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.
Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.
Asunto(s)
Ambiente , Diseño Interior y Mobiliario , PakistánRESUMEN
Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.
Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.
RESUMEN
Advanced computational methods are being actively sought to address the challenges associated with the discovery and development of new combinatorial materials, such as formulations. A widely adopted approach involves domain-informed high-throughput screening of individual components that can be combined together to form a formulation. This manages to accelerate the discovery of new compounds for a target application but still leaves the process of identifying the right "formulation" from the shortlisted chemical space largely a laboratory experiment-driven process. We report a deep learning model, the Formulation Graph Convolution Network (F-GCN), that can map the structure-composition relationship of the formulation constituents to the property of liquid formulation as a whole. Multiple GCNs are assembled in parallel that featurize formulation constituents domain-intuitively on the fly. The resulting molecular descriptors are scaled based on the respective constituent's molar percentage in the formulation, followed by integration into a combined formulation descriptor that represents the complete formulation to an external learning architecture. The use case of the proposed formulation learning model is demonstrated for battery electrolytes by training and testing it on two exemplary data sets representing electrolyte formulations vs battery performance: one data set is sourced from the literature about Li/Cu half-cells, while the other is obtained by lab experiments related to lithium-iodide full-cell chemistry. The model is shown to predict performance metrics such as Coulombic efficiency (CE) and specific capacity of new electrolyte formulations with the lowest reported errors. The best-performing F-GCN model uses molecular descriptors derived from molecular graphs (GCNs) that are informed with HOMO-LUMO and electric moment properties of the molecules using a knowledge transfer technique.
Asunto(s)
Suministros de Energía Eléctrica , Electrólitos , Electrólitos/química , Iones , Ensayos Analíticos de Alto Rendimiento , LitioRESUMEN
Introducción: La normativa existente que obliga a los establecimientos alimentarios a reflejar en el etiquetado la información sobre la presencia de alérgenos de declaración obligatoria no consigue evitar que puedan producirse reacciones adversas accidentales en los consumidores susceptibles. Por ello, en este trabajo se revisa la normativa europea existente en materia de alérgenos y se analizan las causas por las que sigue habiendo alertas sanitarias de alérgenos no declarados, proponiéndose posibles soluciones para solventar este problema. Método: Se ha llevado a cabo una investigación documental desarrollada en cinco etapas. Para ello, se recopiló literatura publicada hasta noviembre de 2022. Resultados: El Reglamento 1169/2011 sobre la información alimentaria facilitada al consumidor establece las normas de etiquetado aplicables a los alérgenos contenidos en los productos. En su artículo 36, una de las informaciones alimentarias voluntarias a incluir es la posible presencia no intencionada en el alimento de sustancias o productos que causen alergias o intolerancias, también conocido como etiquetado precautorio de alérgenos (EPA). Tanto la confusión que existe alrededor del uso del EPA, como la compleja estructura de la cadena alimentaria y, en algunos casos, la formación deficiente del personal, pueden aumentar el riesgo poner en el mercado productos inseguros al alcance de personas susceptibles. Conclusiones: Se considera conveniente intensificar la formación de los trabajadores de cualquier establecimiento alimentario y realizar actos de ejecución que regulen el EPA. (AU)
Introduction: Existing regulations requiring food establishments to label on the presence of mandatory declaration allergen fail to prevent accidental adverse reactions from occurring in susceptible consumers. Therefore, this paper reviews the existing European legislation on allergens and analyses the reasons why health alerts for undeclared allergens continue to occur, proposing possible solutions to solve this problem.Method: Documentary research was carried out in five stages. For this purpose, literature published up to Novem-ber 2022 was collected.Results: Regulation 1169/2011 on the provision of food information to consumers sets out the labelling rules appli-cable to allergens contained in products. In its article 36, one of the voluntary food information to be included is the possible unintended presence in the food of substances or products causing allergies or intolerances, also known as precautionary allergen labelling (PAL). Confusion surrounding the use of PAL, the complex structure of the food chain and, in some cases, poorly trained staff all can increase the risk of placing unsafe products on the market within the reach of susceptible people.Conclusions: It is considered appropriate to intensify the training of workers in all food establishments the PAL. (AU)
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Humanos , Hipersensibilidad a los Alimentos/prevención & control , Etiquetado de Alimentos/legislación & jurisprudencia , Alérgenos , Unión Europea , Industria de AlimentosRESUMEN
Biochemical oxygen demand (BOD) is one of the most important water/wastewater quality parameters. BOD5 is the amount of oxygen consumed in 5 days by microorganisms that oxidize biodegradable organic materials in an aerobic biochemical manner. The primary objective of this research is to apply microbial fuel cells (MFCs) to reduce the time requirement of BOD5 measurements. An artificial neural network (ANN) has been created, and the predictions we obtained for BOD5 measurements were carried out within 6-24 h with an average error of 7%. The outcomes demonstrated the viability of our AI MFC/BES BOD5 sensor in real-life scenarios.
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Fuentes de Energía Bioeléctrica , Técnicas Biosensibles , Análisis de la Demanda Biológica de Oxígeno , Monitoreo del Ambiente , Oxígeno/análisisRESUMEN
Natural selection should favor individuals that synchronize energy-demanding aspects of reproductive activity with periods of high resource abundance and predictability, leading to seasonal patterns of reproduction at the population level. Nonetheless, few studies-especially those on bats in the Neotropics-have used rigorous quantitative criteria to distinguish among phenological patterns for different populations from the same habitat or for the same species in different habitats. To explore such issues, we quantified annual patterns of reproduction in male and in female bats from lowland Amazonia (environs of Iquitos, Peru), and did so at the level of populations and ensembles. Five species exhibited unimodal patterns including Artibeus obscurus, A. planirostris, Carollia benkeithi, Phyllostomus hastatus, and Rhinophylla pumilio. Two species (A. lituratus and Glossophaga soricina) evinced bimodal patterns with reproductive peaks separated by patterns of inactivity, whereas four species (C. brevicauda, C. perspicillata, Sturnira lilium, and S. tildae) evinced a bimodal pattern in which peaks in activity occur in tandem, with the first peak generally markedly higher than the second peak. Frugivore, gleaning animalivore, and nectarivore ensembles exhibited bimodal, unimodal, and bimodal reproductive phenologies, respectively. Nonetheless, interannual variation in phenology (i.e., the monthly timing of peaks within a season rather than the number of peaks per year) characterized four (A. obscurus, C. brevicauda, C. perspicillata, and S. lilium) of the eight species and each of the three ensembles (frugivores, gleaning animalivores, and nectarivores) with adequate sampling. Regardless of interspecific variation in strategies, the phenology of reproduction enhances the likelihood that parturition and recruitment of young into the population occurs during the wet season, the period of likely highest resource abundance. Based on a comparison of our results with those from other well-studied bat populations, four species did not exhibit geographic variation in reproductive phenologies (A. obscurus, G. soricina, C. brevicauda, and R. pumilio), whereas three species evinced such geographic variation (A. lituratus, A. planirostris, and C. perspicillata). Climate change will likely alter the seasons and extents of propitious times for reproductive activities, as well as the reliability of proximate cues for initiating reproduction, compromising current reproductive strategies and leading to altered phenological patterns of reproduction or reproductive success, possibly resulting in local extinction of some species.
La selección natural debería favorecer a individuos que sincronicen aspectos de alta demanda de energía en su actividad reproductiva con períodos de alta abundancia y previsibilidad de recursos, lo que conduciría a patrones estacionales de reproducción a nivel poblacional. No obstante, pocos estudios, especialmente estudios sobre murciélagos en el Neotrópico, han utilizado criterios cuantitativos rigurosos para distinguir entre patrones fenológicos ya sea para diferentes poblaciones dentro del mismo hábitat o para la misma especie en diferentes hábitats. Para explorar este tema, cuantificamos los patrones anuales de reproducción de murciélagos machos (porcentaje de la población con testículos escrotales) y hembras (porcentaje de la población embarazada o lactante) en regiones bajas de la Amazonía (alrededores de Iquitos, Perú) a nivel de poblaciones y de ensamblajes. Cinco especies exhibieron patrones unimodales, incluidos Artibeus obscurus, Artibeus planirostris, Carollia benkeithi, Phyllostomus hastatus, y Rhinophylla pumilio. Dos especies (Artibeus lituratus y Glossophaga soricina) mostraron patrones bimodales, con picos reproductivos separados por patrones de inactividad, mientras que cuatro especies (Carollia brevicauda, Carollia perspicillata, Sturnira lilium, y Sturnira tildae) mostraron un patrón bimodal en el que los picos de actividad ocurren en tándem, con un primer pico considerablemente más alto que el segundo. Los grupos de frugívoros, animalívoros y nectarívoros exhibieron fenologías reproductivas bimodales, unimodales y bimodales respectivamente. No obstante, la variación interanual en la fenología (es decir, el mes dentro de una temporada en que ocurren los picos en lugar del número de picos por año) caracterizó a cuatro (A. obscurus, C. brevicauda, C. perspicillata y S. lilium) de las ocho especies y cada uno de los tres ensamblajes (frugívoros, animalívoros y nectarívoros) con un tamaño de muestra adecuado. Independientemente de la variación en las estrategias, la fenología en la reproducción aumenta la probabilidad de que el parto y el reclutamiento de crías en la población ocurran en la estación húmeda, el período de mayor abundancia de recursos. Cuando comparamos nuestros resultados con los de otras poblaciones de murciélagos mejor estudiadas, cuatro especies no mostraron variación geográfica en sus estrategias reproductivas (A. obscurus, G. soricina, C. brevicauda y R. pumilio), mientras que tres especies si mostraron esta variación geográfica (A. lituratus, A. planirostris y C. perspicillata). Es probable que el cambio climático altere las estaciones y la duración de los periodos propicios para el desarrollo de actividades reproductivas de alta demanda de energía, así como la regularidad de las señales activantes para iniciar la actividad reproductiva, comprometiendo las estrategias reproductivas actuales y conllevando a patrones fenológicos de reproducción alterados, lo que para algunas especies podría resultar en extinciones locales.
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The electrochemical performances and denitrification efficiency of microbial fuel cells (MFCs) are often limited by chemical oxygen demand/nitrogen (COD/N) of wastewater. To overcome this limitation, single-chamber air cathode MFCs with varying COD/N (16/1, 8/1, and 4/1) were established to investigate their electrochemical performances, denitrification efficiency, and bacterial communities. The optimal COD/N for maximizing electricity generation and denitrification efficiency was 8/1, as supported by the greatest corrected coulomb efficiency (13.6%) and electron transfer rate (2.36 C/h for electricity generation, 39.77 C/h for denitrification). As COD/N decreased, the electrochemically active genus Geobacter was replaced by the denitrifying genera Un._f_Burkholderiaceae, Dechlorosoma, and Petrimonas. These results indicated that the efficiency of electricity generation and denitrification was not solely determined by the abundance of electrochemically active and denitrifying bacteria. The presence of a faster electron transfer pathway, possibly direct interspecies electron transfer, enhanced simultaneous electricity generation and denitrification in MFCs with COD/N of 8/1.
Asunto(s)
Fuentes de Energía Bioeléctrica , Análisis de la Demanda Biológica de Oxígeno , Electrones , Bacterias , NitrógenoRESUMEN
Attributable to the prosperous production growth of palm oil in Malaysia, the generated palm oil mill effluent (POME) poses a high threat owing to its highly polluted characteristic. Urged by the escalating concern of environmental conservation, POME pollution abatement and potential energy recovery from the effluent are flagged up as a research topic of interest. In this study, a cutting-edge photocatalytic fuel cell (PFC) system with employment of ZnO/Zn nanorod array (NRA) photoanode, CuO/Cu cathode, and persulfate (PS) oxidant was successfully designed to improve the treatment of POME and simultaneous energy production. The photoelectrodes were fabricated and characterized by field emission scanning electron microscopy with energy (FESEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), and Brunauer, Emmett, and Teller analysis (BET). Owing to the properties of strong oxidant of PS, the proposed PFC/PS system has exhibited exceptional performance, attaining chemical oxygen demand (COD) removal efficiency of 96.2%, open circuit voltage (Voc) of 740.0 mV, short circuit current density (Jsc) of 146.7⯵A cm-2, and power density (Pmax) of 35.6 µW cm-2. The pre-eminent PFC/PS system performance was yielded under optimal conditions of 2.5 mM of persulfate oxidant, POME dilution factor of 1:20, and natural solution pH of 8.51. Subsequently, the postulated photoelectrocatalytic POME treatment mechanism was elucidated by the radical scavenging study and Mott-Schottky (M-S) analysis. The following recycling test affirmed the stability and durability of the photoanode after four continuous repetition usages while the assessed electrical energy efficiency revealed the economic viability of PFC system serving as a post-treatment for abatement of POME. These findings contributed toward enhancing the sustainability criteria and economic viability of palm oil by adopting sustainable and efficient POME post-treatment technology.
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Electricidad , Residuos Industriales , Aceite de Palma/análisis , Residuos Industriales/análisis , Malasia , Análisis de la Demanda Biológica de Oxígeno , Aceites de Plantas/química , Eliminación de Residuos LíquidosRESUMEN
There is a critical need for small molecules capable of rescuing pathophysiological phenotypes induced by alpha-synuclein (aSyn) misfolding and oligomerization. Building upon our previous aSyn cellular fluorescence lifetime (FLT)-Förster resonance energy transfer (FRET) biosensors, we have developed an inducible cell model incorporating the red-shifted mCyRFP1/mMaroon1 (OFP/MFP) FRET pair. This new aSyn FRET biosensor improves the signal-to-noise ratio, reduces nonspecific background FRET, and results in a 4-fold increase (transient transfection) and 2-fold increase (stable, inducible cell lines) in FRET signal relative to our previous GFP/RFP aSyn biosensors. The inducible system institutes greater temporal control and scalability, allowing for fine-tuning of biosensor expression and minimizes cellular cytotoxicity due to overexpression of aSyn. Using these inducible aSyn-OFP/MFP biosensors, we screened the Selleck library of 2684 commercially available, FDA-approved compounds and identified proanthocyanidins and casanthranol as novel hits. Secondary assays validated the ability of these compounds to modulate aSyn FLT-FRET. Functional assays probing cellular cytotoxicity and aSyn fibrillization demonstrated their capability to inhibit seeded aSyn fibrillization. Proanthocyanidins completely rescued aSyn fibril-induced cellular toxicity with EC50 of 200â nM and casanthranol supported a 85.5% rescue with a projected EC50 of 34.2â µM. Furthermore, proanthocyanidins provide a valuable tool compound to validate our aSyn biosensor performance in future high-throughput screening campaigns of industrial-scale (million-compound) chemical libraries.
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Técnicas Biosensibles , Emodina , Proantocianidinas , alfa-Sinucleína/metabolismo , Transferencia Resonante de Energía de Fluorescencia/métodos , Ensayos Analíticos de Alto RendimientoRESUMEN
Enediyne antibiotics are a striking family of DNA-cleaving natural products with high degrees of cytotoxicity and structural complexity. Microbial genome sequences, which have recently accumulated, point to an untapped trove of "cryptic" enediynes. Most of the cognate biosynthetic gene clusters (BGCs) are sparingly expressed under standard growth conditions, making it difficult to characterize their products. Herein, we report a fluorescence-based DNA cleavage assay coupled with high-throughput elicitor screening for the rapid, targeted discovery of cryptic enediyne metabolites. We applied the approach to Streptomyces clavuligerus, which harbors two such BGCs with unknown products, identified steroids as effective elicitors, and characterized 10 cryptic enediyne-derived natural products, termed clavulynes A-J with unusual carbonate and terminal olefin functionalities, with one of these congeners matching the recently reported jejucarboside. Our results contribute to the growing repertoire of enediynes and provide a blueprint for identifying additional ones in the future.
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Productos Biológicos , Productos Biológicos/química , Transferencia Resonante de Energía de Fluorescencia , Ensayos Analíticos de Alto Rendimiento , Antibacterianos , Enediinos/química , Familia de MultigenesAsunto(s)
Sistemas CRISPR-Cas , Producción de Cultivos , Productos Agrícolas , Unión Europea , Edición Génica , Plantas Modificadas Genéticamente , Sistemas CRISPR-Cas/genética , Producción de Cultivos/legislación & jurisprudencia , Producción de Cultivos/métodos , Productos Agrícolas/genética , Edición Génica/legislación & jurisprudencia , Plantas Modificadas Genéticamente/genéticaAsunto(s)
Dióxido de Carbono , Carbono , Cooperación Internacional , Energía Renovable , Desarrollo Sostenible , Carbono/provisión & distribución , Dióxido de Carbono/provisión & distribución , Energía Renovable/economía , Energía Renovable/legislación & jurisprudencia , Desarrollo Sostenible/economía , Desarrollo Sostenible/legislación & jurisprudencia , Desarrollo Sostenible/tendencias , Cooperación Internacional/legislación & jurisprudenciaRESUMEN
We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA's function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening two different small validation libraries using novel microplate readers that detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from FRET-HTS of 50,000 compounds using the same biosensor, with hit compounds functionally evaluated using assays for Ca2+-ATPase activity and Ca2+-transport. We focused on 18 hit compounds, from which we identified eight structurally unique scaffolds and four scaffold classes as SERCA modulators, approximately half of which are activators and half are inhibitors. Five of these compounds were identified as promising SERCA activators, one of which activates Ca2+-transport even more than Ca2+-ATPase activity thus improving SERCA efficiency. While both activators and inhibitors have therapeutic potential, the activators establish the basis for future testing in heart disease models and lead development, toward pharmaceutical therapy for heart failure.
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Transferencia Resonante de Energía de Fluorescencia , Insuficiencia Cardíaca , Humanos , Ensayos Analíticos de Alto Rendimiento , Corazón , Insuficiencia Cardíaca/tratamiento farmacológico , Adenosina TrifosfatasasRESUMEN
Small molecules that bind to allosteric sites on target proteins to alter protein function are highly sought in drug discovery. High-throughput screening (HTS) assays are needed to facilitate the direct discovery of allosterically active compounds. We have developed technology for high-throughput time-resolved fluorescence lifetime detection of fluorescence resonance energy transfer (FRET), which enables the detection of allosteric modulators by monitoring changes in protein structure. We tested this approach at the industrial scale by adapting an allosteric FRET sensor of cardiac myosin to high-throughput screening (HTS), based on technology provided by Photonic Pharma and the University of Minnesota, and then used the sensor to screen 1.6 million compounds in the HTS facility at Bristol Myers Squibb. The results identified allosteric activators and inhibitors of cardiac myosin that do not compete with ATP binding, demonstrating high potential for FLT-based drug discovery.
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Transferencia Resonante de Energía de Fluorescencia , Ensayos Analíticos de Alto Rendimiento , Ensayos Analíticos de Alto Rendimiento/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos , Miosinas Cardíacas , Descubrimiento de Drogas/métodosRESUMEN
The MUS81-EME1/2 structure-specific endonucleases play a crucial role in the processing of stalled replication forks and recombination intermediates, and have been recognized as an attractive drug target to potentiate the anti-cancer efficacy of DNA-damaging agents. Currently, no bioactive small-molecule inhibitors of MUS81 are available. Here, we performed a high-throughput small-molecule inhibitors screening, using the FRET-based DNA cleavage assay. From 7920 compounds, we identified dyngo-4a as a potent inhibitor of MUS81 complexes. Dyngo-4a effectively inhibits the endonuclease activities of both MUS81-EME1 and MUS81-EME2 complexes, with IC50 values of 0.57 µM and 2.90 µM, respectively. Surface plasmon resonance (SPR) and electrophoretic mobility shift assay (EMSA) assays reveal that dyngo-4a directly binds to MUS81 complexes (KD â¼ 0.61 µM) and prevents them from binding to DNA substrates. In HeLa cells, dyngo-4a significantly suppresses bleomycin-triggered H2AX serine 139 phosphorylation (γH2AX). Together, our results demonstrate that dyngo-4a is a potent MUS81 inhibitor, which could be further developed as a potentially valuable chemical tool to explore more physiological roles of MUS81 in the cells.
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Proteínas de Unión al ADN , Endodesoxirribonucleasas , Humanos , Endodesoxirribonucleasas/química , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Proteínas de Unión al ADN/química , Células HeLa , Transferencia Resonante de Energía de Fluorescencia , Ensayos Analíticos de Alto Rendimiento , Endonucleasas/metabolismo , Replicación del ADN , ADN/metabolismoAsunto(s)
Unión Europea , Investigadores , Apoyo a la Investigación como Asunto , Investigación , Unión Europea/economía , Unión Europea/organización & administración , Reino Unido , Investigadores/economía , Investigadores/legislación & jurisprudencia , Apoyo a la Investigación como Asunto/economía , Apoyo a la Investigación como Asunto/legislación & jurisprudencia , Investigación/economía , Investigación/legislación & jurisprudenciaRESUMEN
Lymphocyte activation gene 3 (LAG-3) is a negative immune checkpoint and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. Fibrinogen-like protein 1 (FGL1) is a major LAG-3 functional ligand that is upregulated in various human cancers. LAG-3 positive T cells bind FGL1 expressed by cancer cells, which inhibits T-cell activation and cytokine secretion via indirect blocking of T cell receptor (TCR) signaling. High expression of LAG-3 and FGL1 in patients with solid tumors is associated with drug resistance and decreased survival in response to FDA-approved immune checkpoint inhibitors. Therefore, targeting the LAG-3/FGL1 pathway represents a promising therapeutic strategy to maximize the number of patients benefiting from checkpoint blockade therapy. However, there are no small molecules in existence that target LAG-3/FGL1 interaction. Herein, we report a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate the ability of small molecules to inhibit LAG-3/FGL1 interaction. We further demonstrate the implementation of the developed assay in screening chemical libraries of small molecules from the NCI Diversity Set VII, FDA-approved drugs, and a focused library of NF-κB modulators. This work will pave the way for drug discovery efforts focused on therapeutic targeting of LAG-3/FGL1 interaction using small molecules.
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Transferencia Resonante de Energía de Fluorescencia , Ensayos Analíticos de Alto Rendimiento , Humanos , Descubrimiento de Drogas , Bibliotecas de Moléculas Pequeñas/farmacología , Activación de Linfocitos , FibrinógenoRESUMEN
The sustainable development of human society in today's high-tech world depends on some form of eco-friendly energy source because existing technologies cannot keep up with the rapid population expansion and the vast amounts of wastewater that result from human activity. A green technology called a microbial fuel cell (MFC) focuses on using biodegradable trash as a substrate to harness the power of bacteria to produce bioenergy. Production of bioenergy and wastewater treatment are the two main uses of MFC. MFCs have also been used in biosensors, water desalination, polluted soil remediation, and the manufacture of chemicals like methane and formate. MFC-based biosensors have gained a lot of attention in the last few decades due to their straightforward operating principle and long-term viability, with a wide range of applications including bioenergy production, treatment of industrial and domestic wastewater, biological oxygen demand, toxicity detection, microbial activity detection, and air quality monitoring, etc. This review focuses on several MFC types and their functions, including the detection of microbial activity.