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Palladium (Pd) membranes are a crucial device for separating hydrogen and are usually operated at normal pressure on the permeate side with a single outlet. Instead of these common operating conditions, the difference between using a double outlet and a single outlet is studied. Four different vacuum degrees (15–60 kPa) are applied on the permeate side, and the results are compared with the non-vacuum operations. Situations under the vacuum and the effects of temperatures (300–400 °C) on H2 permeation are discussed. Finally, the influences of different feed gas mixtures (H2/N2, H2/CO2, and H2/CO) on the Pd membrane performance are investigated. The results show that there is no difference in H2 permeation impact the single outlet and the double outlet on the permeate side. When a vacuum is imposed on the permeate side, the H2 permeation rate and H2 recovery are efficiently intensified, that is, when the pressure difference is 9 atm, they increase from 73.21 to 84.51% and from 0.0035378 to 0.0040808 mol∙s−1, respectively. Moreover, the H2 recovery can be improved to up to 68.44% under a vacuum degree of 60 kPa. At a given Reynolds number, an increase in temperature increases the H2 permeation rate but lowers its recovery, stemming from more H2 in the feed gas. This study also investigates the feed gas of H2/N2 under a vacuum to provide a useful insight into H2 production and separation from ammonia, and the results are compared with two different feed gases of H2/CO2 and H2/CO mixtures. The results suggest that the impurities (i.e., N2, CO2, and CO) have a negative influence on the Pd membrane, which causes the H2 permeation rate to decrease, and the effect of N2 is the least significant compared to the other two.

INTRODUCTION AND OBJECTIVES Advanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. METHODS This cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. RESULTS The 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P

Hydrogen is a renewable gas, efficient to produce energy that makes it a suitable alternative and effective solution for a carbon-free environment. Unlike other fossil fuels, combustion of hydrogen does not produce toxic compounds, such as greenhouse gases, carbon monoxide, hydrocarbons, etc., resulting in less environmental pollution. Agro-industrial residues contain several lignocelluloses that favor the growth of microorganisms to produce valuable products such as hydrogen. Of the diverse techniques in hydrogen production, bioconversion proves to be an efficient method in permuting agro-industrial residues into hydrogen. This review provides detailed information on the bioconversion processes and factors involved in hydrogen production from agro-industrial residues including different fermentation processes such as dark fermentation and photo-fermentation, and fuel cell systems such as microbial electrolysis cell and microbial fuel cell. Different pretreatment techniques to enhance the availability of lignocellulose for hydrogen production have been elaborated in this review. Various factors including pH, temperature and nutrient composition of feed, affecting the production efficiency and purity of the products during fermentation have been discussed.

Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th.82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS.Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros.Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d’Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020.Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio.La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

Sunlight-powered reduction of CO2 to fuels and chemicals is a promising strategy to close the carbon loop and facilitate the energy transition. In this research, we demonstrate that Au nanoparticles supported on TiO2 are an efficient plasmonic catalyst for the sunlight-powered reverse water-gas shift (rWGS) reaction. A maximum CO production rate of 429 mmol g(Au)(-1) h(-1) with a selectivity of 98 % and an apparent quantum efficiency of 4.7 % were achieved using mildly concentrated sunlight (1.44 W cm(-2) equals 14.4 sun). The CO production rate showed an exponential increase with increasing light intensity, suggesting that the process is mainly promoted by a photothermal effect. Thermal reference experiments with the same catalysts promoted CH4 formation, dropping the CO selectivity to 70 %. Thus, mildly concentrated sunlight can efficiently and selectively enhance the promotion of the rWGS reaction without using external heating. European Fund for Regional Development through the cross border collaborative Interreg V program Flanders-The Netherlands (project LUMEN); Belgian province of Limburg; Dutch province of Limburg; Dutch province of Noord-Brabant; Solliance

Skeletonema costatum is a diatom widely distributed in red tide microalgae blooms and as one of the main algae causing harmful algal blooms, because of their rapid reproduction and production of toxic and harmful substances, often play a negative role in aquatic ecosystems, and human health and wellbeing. Bacillomycin D is a nonribosomal cyclic antifungal lipopeptide in the iturins family. In this study, synthetic Bacillomycin D was tested for its ability to inhibit the growth of S. costatum. The EC50. 24h of Bacillomycin D on S. costatum was 24.70 μg/mL. The chlorophyll fluorescence parameters Fv/Fm, Fv/Fo, and yield of the diatoms decreased significantly with increasing concentrations of Bacillomycin D. Study of the mechanism showed that Bacillomycin D induced cell death by changing cell membrane permeability, promoting the release of cellular contents. In this study, transcriptomic analysis showed Bacillomycin D significantly inhibited the photosynthesis and metabolism of S. costatum. These findings investigated the inhibitory effect of Bacillomycin D on the growth of S. costatum and provided a theoretical foundation for the development of new environmentally friendly biological algicide.

Contains fulltext : 248871.pdf (Publisher’s version ) (Open Access) BACKGROUND: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. OBJECTIVE: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. METHODS: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). RESULTS: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. CONCLUSION: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

The impact of different nitrogen sources on the microalga, Chlorella vulgaris, was studied in a newly developed microalgal-bacterial photobioreactor via a dual nutrient heterogeneity mode. The mechanisms of nitrogen transformation and valorisation were unveiled, and subsequently, optimized via dual nutrient heterogeneity feeding modes comprising of various NH4+-N and NO3−-N concentrations. The nitrogen-assimilation mechanism from the microalgal-bacterial consortium was found to reduce microalgal growth inhibition, stemming at high NH4+-N concentrations. Accordingly, the total nitrogen removal efficiency was enhanced from 40.91% to 96.38% accompanied with maximum microalgal biomass production of up to 792 mg/L at a balanced or higher NH4+-N loading from mixed nitrogen environment. The harvested microalgal biomass contained high lipid accumulation of approximately 30% when fed with optimum NH4+-N and NO3−-N loadings at 60 and 58 mg/d, respectively. At this mixed nitrogen species loadings, high unsaturated fatty acid methyl esters (FAME) were attained. Indeed, the major FAME species (97%–100%) fell within the C16-18 range, signifying biodiesel characteristics conformity to the requirements for quality biodiesel application. Therefore, the dual heterogeneity modes of balanced NH4+-N and NO3−-N loadings into photobioreactor could offer effective microalgal nitrogen assimilation for sustainable wastewater treatment and microalgae-based biodiesel production simultaneously.

This study contributes to anti-malarial research effort by conducting in silico assessment of 125 compounds originated from Cannabis sativa L. against plasmodium falciparum dihydrofolate reductase-thymidinesynthase (pfDHFR-TS) enzyme for potential inhibition activity. Drug-like and pharmacokinetic criteria were used to assess the drug-like properties of the studied compounds. AutoDock4.2.6 and AutoDock Vina software were used to calculate the possible binding pose of the studied compounds to pfDHFR-TS enzyme. The docking procedure was validated using two known inhibitors cycloguanil and WR99210. 65 out of 125 compounds violated no more than 2 of Lipinski’s rule of five and were sorted out as favorable for drug development. Amongst these 65 compounds, pharmacokinetic properties and toxicity evaluation identified 60 compounds that meet the criteria of drug-like properties and were subjected to further docking studies. Docking outcomes identified 10 compounds including compounds 4, 9, 19, 22, 23, 25, 30, 42, 43, and 59 as potential candidates for inhibiting the function of pfDHFR-TS at the active site through hydrogen bonds with Ile14, Asp54, and Ile 164 residues. Compound 9 is considered as the top “hit” with docking energy far more exceeding those of the standard compounds. High correlation coefficient between the docking energy of AutoDock4.2.6 and AutoDock Vina was recorded with the value of R 2 = 0.74.

Despite significant advances in silicon photonics, optical packaging and interconnection of photonic integrated circuits constitutes a large portion of the associated manufacturing costs. Optical fibers are the dominant approach to optical interconnection. However, techniques that rely on fibers lack scalability, have low efficiency and show poor misalignment tolerance. Proposed alternative solutions using polymer waveguides have shown improved coupling efficiency, misalignment tolerance and scalability. Here we present the design, simulation and the experimental confirmation of an adiabatic silicon nitride taper to polymer waveguide coupler with only 0.52 dB of TE coupling loss at 1550-nm wavelength, excluding material loss. The coupler demonstrates $\pm 4~\mu \text{m}$ of lateral misalignment tolerance with a 1-dB penalty which, to the best of our knowledge, is the highest reported tolerance for silicon nitride to polymer waveguide coupling.

Background With the advent of the 21st century, natural food products and functional food ingredients have been heavily marketed as additives to improve human health and well-being. Although the early iterations were chemically synthesized, more emphasis on natural raw materials for pharmaceutical products shifted the focus towards microorganisms such as algae Scope and approach Algae are known to contain a wide range of functional components, such as carotenoids, chlorophyll, docosahexaenoic acid, eicosapentaenoic acid, and astaxanthin. These components possess numerous benefits for value-added food applications and are widely sought after in the current market. Due to the high expenditure related to the production of these nutraceutical items, researchers are looking towards enhancing the yield with the help of nanotechnology. Key findings and conclusions Algae also proved to be a safe and cheaper alternative in the production of nanoparticles (NPs), which demonstrate a range of antimicrobial properties. Additionally, algae secrete various important biomolecules and bioactive components upon exposure to nanoparticles which can be utilized in the pharmaceutical industry. Further research focused on improving biomolecules secretion and sustainable NPs production is necessary for the exponential growth of this sector in the industrial world. This review highlights the studies conducted in the field of nanotechnology mediated with algae to enhance the generation of pharmaceuticals and nutraceuticals.

Hydrogen (H2) is a carbon-free clean energy source and can be generated from water by electrolysis. The fabrication of highly sustainable electrode materials to replace expensive platinum is vital for the supportable production of molecular hydrogen via electrolysis of water. Nickel based electrode materials have attracted a great attention in the water splitting reaction. In this context, supporting material such as carbon is adopted to increase the catalytic activity. In this study, a special route was advanced to construct carbon supported Ni3N/Ni, which was as an effective electrocatalyst for hydrogen evolution reaction (HER) in both 0.5 M H2SO4 and 1 M KOH electrolytes. We observed that the carbon support can effectively improve the electronic structure of Ni3N/Ni by introducing intrinsic active sites. The optimized Ni3N/Ni@C composite showed superior electrical conductivity and charge transfer rate. Consequently, the Ni3N/Ni@C750 °C composite showed enhanced electrocatalytic behaviour with a small overpotential of 163 and 172 mV to attain an optimal current density of 10 mA cm−2 and durability over 1000 cycles in acid and alkaline electrolytes towards HER application.

Microalgae are a promising feedstock for carbon-neutral biofuel production due to their superior cellular composition. Alternatively, oxidative torrefaction has been recognized as a potential thermochemical technique for microalgal solid biofuel upgrading. Herein, by using microalga N. oceanica as a feedstock, several characterizations are adopted for evaluating the potential of oxidative torrefaction towards microalgal solid biofuel production. The oxidatively torrefied microalgae can be upgraded as lignite. After in-depth analysis, significant change in the surface microstructure of oxidatively torrefied microalgae is largely changed (via wrinkle and fragmentation) The hydrophobicity, thermal decomposition, thermal stability, and aromatization of oxidatively torrefied microalgae can be largely enhanced as the oxidative torrefaction severity increase. With the increasing torrefaction temperature, the hydrophobicity of oxidative torrefied microalgae gradually improved. The decomposition of C-2/3/5, and −OCH3, the CO bonds of CH3CO-, and the aromatization occurs via oxidative torrefaction according to the NMR analysis. For XPS analysis, torrefaction operation significantly decreases the carbide carbon and enhances the graphitization. As a result, the thermal stability of oxidatively torrefied microalgae is improved. Conclusively, the information obtained in this study can provide insights into the evaluation of oxidative torrefaction performance and fuel properties of microalgal solid biofuel, which may help accelerate the advancement of oxidative torrefaction industrialization.

Cylinder-shaped NaY zeolite was used as an adsorbent for eradicating both heavy metal ions (Cu2+, Zn2+, Ni2+, and Co2+) and proteins from the waste streams. As a pseudo-metal ion affinity adsorbent, NaY zeolite was used in the capture of heavy metal ions in the first stage. The amount (molar basis) of metal ions adsorbed onto NaY zeolite decreased in the order of Cu2+ > Zn2+ > Co2+ > Ni2+. Bovine serum albumin (BSA) was utilized as a model of proteins used in the waste adsorption process by NaY zeolite. The adsorption capacities of NaY zeolite and Cu/NaY zeolite for BSA were 14.90 mg BSA/g zeolite and 84.61 mg BSA/g zeolite, respectively. Moreover, Cu/NaY zeolite was highly stable in the solutions made of 2 M NaCl, 500 mM imidazole or 125 mM EDTA solutions. These conditions indicated that the minimal probability of secondary contamination caused by metal ions and soluble proteins in the waste stream. This study demonstrates the potential of Cu/NaY zeolite complex as an efficient pseudo-metal chelate adsorbent that could remove metal ions and water-soluble proteins from wastewater concurrently.

Ibrutinib demonstrated robust efficacy, regardless of high-risk features, in previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL). The IBRORS-CLL study supports the effectiveness and the manageable safety profile of single-agent ibrutinib, which was not adversely affected by high-risk characteristics in real-world CLL patients in Spain. We also found a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status. Background: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain.Patients: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019. Results: A total of 269 patients were included (median age: 70.9 years; cardiovascular comorbidity: 55.4%, including hypertension [47.6%] and atrial fibrillation [AF] [7.1%]). Overall, 96.7% and 69% of patients underwent molecular testing for del(17p)/TP53 mutation and IGHV mutation status. High-risk genetic features included unmutated IGHV (79%) and del(17p)/TP53 mutation (first-line: 66.3%; second-line: 23.1%). Overall, 84 (31.2%) patients received ibrutinib as first-line treatment, and it was used as second- and third-line therapy in 121 (45.0%) and 64 (23.8%) patients. The median progression-free survival and overall survival were not reached irrespective of del(17p)/TP53, or unmutated IGHV. Common grade >= 3 adverse events were infections (122%) and bleeding (3%). Grade >= 3 AF occurred in 1.5% of patients. Conclusion: This real-world study shows that single-agent ibrutinib is an effective therapy for CLL, regardless of age and high-risk molecular features, consistent with clinical trials. Additionally, single-agent ibrutinib was well tolerated, with a low rate of cardiovascular events. This study also emphasized a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status in clinical practice according to guideline recommendations. (C) 2021 The Author(s). Published by Elsevier Inc.

The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling., This study explores the role of ATPase inhibitory factor 1 (IF-1) in neuronal function, revealing that IF-1-mediated changes in ATP synthase modulate the production of mitochondrial reactive oxygen species, and that these changes influence synaptic transmission and cognition.

Arsenic-contaminated water is a major concern in many areas worldwide, causing several diseases such as cancer. There is therefore a need for advanced methods to clean waters because conventional methods have drawbacks such as generation of hazardous sludge, heavy operation and high costs. Here we review arsenic sources, chemistry, toxicity and remediation methods. We discuss also sociological aspects of arsenic prevention. Sources include surface water, groundwater and seawater. Methods include bioremediation, phyto-remediation and biofilters. Sociological aspects are public awareness, sharing information on arsenic-free water sources, removing As at the household level, building a community plant and training facilitators.

Oxidant-free Au(I)/Au(III) catalysis can still be regarded as a young and promising chemistry. Because the first examples of gold catalysis were limited to the activation and functionalization of π-C−C bonds and very little was known on fundamental organometallic transformations at gold, countless works during the past 15 years have been devoted to disclosing the elementary reactivity of gold and implementing it in catalysis. Remarkably, great emphasis on triggering oxidative addition at Au(I) has been placed, as the high redox potential of the Au(I)/Au(III) pair disfavors this reaction. In fact, different strategies such as strain release, ligand design and photochemistry have been proven successful at allowing the bottleneck oxidative addition to occur. These approaches have led to the rational development of oxidant-free Au(I)/Au(III) redox catalysis, particularly catalytic cycles in cross-coupling transformations where oxidative addition is usually the entry point to the cycle. Herein, the background story, the development process, and relevant examples of oxidant-free gold-catalyzed cross-coupling reactions are reviewed We acknowledge financial support from MINECO-Spain forprojects PID2019-104498GB- I00 and a FPU PhD grant to P.F.Generalitat de Catalunya is also acknowledged for project2017SGR264

Summary The use of the methylotrophic yeast Pichia pastoris (Komagataella phaffi) to produce heterologous proteins has been largely reported. However, investigations addressing the potential of this yeast to produce bulk chemicals are still scarce. In this study, we have studied the use of P. pastoris as a cell factory to produce the commodity chemical 3‐hydroxypropionic acid (3‐HP) from glycerol. 3‐HP is a chemical platform which can be converted into acrylic acid and to other alternatives to petroleum‐based products. To this end, the mcr gene from Chloroflexus aurantiacus was introduced into P. pastoris. This single modification allowed the production of 3‐HP from glycerol through the malonyl‐CoA pathway. Further enzyme and metabolic engineering modifications aimed at increasing cofactor and metabolic precursors availability allowed a 14‐fold increase in the production of 3‐HP compared to the initial strain. The best strain (PpHP6) was tested in a fed‐batch culture, achieving a final concentration of 3‐HP of 24.75 g l−1, a product yield of 0.13 g g−1 and a volumetric productivity of 0.54 g l−1 h−1, which, to our knowledge, is the highest volumetric productivity reported in yeast. These results benchmark P. pastoris as a promising platform to produce bulk chemicals for the revalorization of crude glycerol and, in particular, to produce 3‐HP., Production of 3‐HP through the Malonyl‐CoA pathway was achieved in Pichia pastoris. Expressing the two subunits of the Malonyl‐CoA reductase separately led to a substantial increase in 3‐HP production. Further metabolic engineering to increase precursors availability increased the 3‐HP titre, achieving a final product concentration of 24.75 g l−1 in fed‐batch cultures, and the highest 3‐HP volumetric productivity value reported for yeast to date (0.54 g l−1 h−1).

New pandemic infection of coronaviridae family virus spread to more than 210 countries with total infection of 1,136,851 and 62,955 (4.6%) deaths until 5th April 2020. Which stopped the regular cycle of humankind but the nature is consistently running. There is no micro molecule remedy found yet to restore the regular life of people. Hence, we decided to work on natural biophores against the COVID proteins. As a first step, major phytoconstituents of antiviral herbs like Leucas aspera, Morinda citrifolia, Azadirachta indica, Curcuma longa, Piper nigrum, Ocimum tenuiflorum, and Corallium rubrum collected and performed the lock and key analysis with major spike protein of COVID-19 to find the best fitting lead biophore using computational drug design platform. The results of protocol run showed, phytoconstituents of Morinda citrifolia and Leucas aspera were found lower binding energy range of − 55.18 to − 25.34 kcal/mol, respectively and compared with Hydroxychloroquine (HCQ) (− 24.29 kcal/mol) and Remdesivir (− 25.38 kcal/mol). The results conclude that, core skeletons chromen, anthracene 9, 11 dione and long-chain alkyl acids/ester-containing biophores showen high stable antagonistic affinity with S-protein. Which leads the breakdown of spike protein and ACE2 receptor complex formation and host mechanism of corono virus. In addition, the dynamic trajectory analysis confirmed the complete denaturation of spike protein by the molecule 4-(24-hydroxy-1-oxo-5-n-propyltetracosanyl)-phenol from Leucas aspera and stability of spike-ligand complex. These biophores will aid the researcher to fabricate new promising analogue and being recommended to assess its COVID-19 treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s12033-021-00358-z.

Chemical descriptors encode the physicochemical and structural properties of small molecules, and they are at the core of chemoinformatics. The broad release of bioactivity data has prompted enriched representations of compounds, reaching beyond chemical structures and capturing their known biological properties. Unfortunately, bioactivity descriptors are not available for most small molecules, which limits their applicability to a few thousand well characterized compounds. Here we present a collection of deep neural networks able to infer bioactivity signatures for any compound of interest, even when little or no experimental information is available for them. Our signaturizers relate to bioactivities of 25 different types (including target profiles, cellular response and clinical outcomes) and can be used as drop-in replacements for chemical descriptors in day-to-day chemoinformatics tasks. Indeed, we illustrate how inferred bioactivity signatures are useful to navigate the chemical space in a biologically relevant manner, unveiling higher-order organization in natural product collections, and to enrich mostly uncharacterized chemical libraries for activity against the drug-orphan target Snail1. Moreover, we implement a battery of signature-activity relationship (SigAR) models and show a substantial improvement in performance, with respect to chemistry-based classifiers, across a series of biophysics and physiology activity prediction benchmarks., Small molecules bioactivity descriptors are enriched representations of compounds, reaching beyond chemical structures and capturing their known biological properties. Here the authors present a collection of deep neural networks able to infer bioactivity signatures for any compound of interest, even when little or no experimental information is available for them.

The objective of this study is to develop a simple protocol to isolate and characterise small extracellular vesicles (sEVs) from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSCs were characterised through analysis of morphology, immunophenotyping and multidifferentiation ability. SEVs were successfully isolated by ultrafiltration from the conditioned medium of hUC-MSCs. The sEVs' size distribution, intensity within a specific surface marker population were measured with zetasizer or nanoparticle tracking analysis. The expression of surface and internal markers of sEVs was also assessed by western blotting. Morphology of hUC-MSCs displayed as spindle-shaped, fibroblast-like adherent cells. Phenotypic analysis by flow cytometry revealed that hUC-MSCs expressed MSC surface marker, including CD90, CD73, CD105, CD44 and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. Populations of sEVs with CD9, CD63 and CD81 positive were detected with size distribution in the diameter of 63.2 to 162.5 nm. Typical sEVs biomarkers such as CD9, CD63, CD81, HSP70 and TSG101 were also detected with western blotting. Our study showed that sEVs from hUC-MSCs conditioned medium were successfully isolated and characterised. Downstream application of hUC-MSCs-sEVs will be further explored.

Cryogenic carbon dioxide (CO2) capture technologies showed promising results for the purification of highly sour natural gas reserves. However, quantitative experimental data for solid and liquid CO2 formation during cryogenic separation is not adequately examined in the previous studies. Moreover, an economical and efficient cryogenic CO2 capture technology with reduced energy and hydrocarbon losses is necessary to make it attractive for commercial use. A high-pressure cryogenic hybrid network comprised of the packed bed and the cryogenic separator was developed for the cryogenic experimental study on CO2 capture from binary CO2-CH4 mixture to focus these areas. Feed containing 30, 50 and 70 % CO2 content were used and the separation study was conducted in vapor-solid (V-S), vapor-liquid (V-L), and vapor-liquid-solid (V-L-S) regions of phase equilibria. The packed bed was used in the V-S operational domain to quantify CO2 solid up to 20 bar because of the operational limitations. Separation characteristics and V-L isothermal flash measurements at 20, 30, and 40 bar pressure and temperature ranges from -20 to −60 °C were carried out in the cryogenic separator. The operation in the setups was carried out at different compositions of the CH4-CO2 binary mixture to define the boundaries of the hybrid cryogenic network. Liquid formation at 40 bar for 70% CO2 feed was 0.15 kg at -55 °C as compared to 0.03 kg for 30 % CO2 feed. The simulation study was carried out using Aspen Plus along with the Peng Robinson Equation of State (EoS), and the results were compared with the experimental data, which showed good agreement. The hybrid cryogenic network showed an energy reduction of 37 % compared to the conventional cryogenic distillation network with 90.6 to 97.3 % CH4 purity and 2.65 to 12.39 % methane losses with different arrangements of the hybrid cryogenic network.

Virgin coconut oil is a useful substance in our daily life. It contains a high percentage of lauric acid which has many health benefits. The current industry has developed several methods to extract the oil out from the coconut fruit. This review paper aims to highlight several common extraction processes used in modern industries that includes cold extraction, hot extraction, low-pressure extraction, chilling, freezing and thawing method, fermentation, centrifugation, enzymatic extraction and supercritical fluid carbon dioxide. Different extraction methods will produce coconut oil with different yields and purities of lauric acid, thus having different uses and applications. Challenges that are faced by the industries in extracting the coconut oil using different methods of extraction are important to be explored so that advancement in the oil extraction technology can be done for efficient downstream processing. This study is vital as it provides insights that could enhance the production of coconut oil.

In-situ transesterification of wet microalgae is one of the emerging methods to produce biodiesel as this approach exclude energy-intensive steps (e.g. drying and lipid extraction) through process merging. Nevertheless, studies related to reaction kinetics and thermodynamic of such process are still limited in the literature while this information are necessary for process design and intensification. Thus, the present study was aimed to evaluate the reaction kinetics and thermodynamics of in-situ transesterification of wet Chlorella vulgaris. It was found that the fatty acid esters (FAE) yield was increased with reaction time and temperature due to gradual conversion of esterifiable lipids to FAE and higher kinetic energy of reactants. In-situ transesterification of C. vulgaris at 60 °C resulted high FAE yields (>90 wt.%) within a short reaction duration (25–35 min). The in-situ transesterification of C. vulgaris was found to follow first order of overall reaction (with respect to esterifiable lipids) and attained activation energy (EA) of 50.4–60.4 kJ/mol. In addition, the in-situ transesterification of wet C. vulgaris is an endothermic (ΔH = 50.4–60.4 kJ/mol) and non-spontaneous (ΔG = 87.7–88.4 kJ/mol) reaction that decreased the randomness of reaction system (ΔS = −0.082 to −0.114 kJ/mol K).

The synthesis and characterization of four platinum(II) complexes using azobenzenes conveniently functionalized as ligands has been carried out. The characteristic photochemical behavior of the complexes due to the presence of azobenzene-type ligands and the role of the ligands in the activation of the complexes has been studied. Their promising cytotoxicity observed in HeLa cells prompted us to study the mechanism of action of these complexes as cytostatic agents. The interaction of the compounds with DNA, studied by circular dichroism, revealed a differential activity of the Pt(II) complexes upon irradiation. The intercalation abilities of the complexes as well as their reactivity with common proteins present in the blood stream allows to confirm some of the compounds obtained as good anticancer candidates.

The enhanced catalytic activity of permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, largely depends on both the experimental conditions used to prepare crystalline hydroxyapatite from its calcium and phosphate precursors and the polarization process parameters. A mineral similar to brushite, which is an apatitic phase that can evolve to hydroxyapatite, is found at the surface of highly crystalline hydroxyapatite. It appears after chemical precipitation and hydrothermal treatment performed at 150 °C for 24 h followed by a sinterization at 1000 °C and a polarization treatment by applying a voltage of 500 V at high temperature. Both the high crystallinity and the presence of brushite-like phase on the electrophotocatalyst affect the nitrogen and carbon fixation under mild reaction conditions (95 °C and 6 bar) and the synthesis of glycine and alanine from a simple gas mixture containing N2, CO2, CH4 and H2O. Thus, the Gly/Ala ratio can be customized by controlling the presence of brushite on the surface of the catalyst, enabling to develop new strategies to regulate the production of amino acids by nitrogen and carbon fixation.

Biohydrogen production from biomass waste, not only addresses the energy demand in a renewable manner but also resolves the safe disposal issues associated with these biowastes. Also, scalable and low-cost techniques to enhance biohydrogen production have gained more attraction and are highly explored. In this research work, date-palm fruit wastes have been studied for their biohydrogen production potential using Enterobacter aerogenes by dark fermentation. Hydrogen yield and productivity were improved through the addition of iron oxide nanoparticles (Fe3O4 NPs) and its date seed activated carbon nanocomposites (Fe3O4/DSAC) to the fermentation media. Studies on discrete inclusions of these NPs showed that the appropriate dosage of NPs promoted, while higher dosages repressed the hydrogen production performance. Optimal dosage and fermentation time was observed as 150 mg/L and 24 h for both the additives. Fe3O4/DSAC nanocomposites showed better hydrogen production enhancement than Fe3O4 NPs. Maximum hydrogen yield of 238.7 mL/g was obtained for the 150 mg/L nanocomposites, which was 65.7% higher than that of the standalone Fe3O4 NPs and three folds higher than the yield of the control run without any NPs inclusion (78.4 mL/g). Metabolites analysis showed that the hydrogen evolution followed the ethanol-acetate pathway. Formation levels of longer chain propionate and butyrate co-metabolites were significantly low in the presence of Fe3O4/DSAC than Fe3O4. The carbon support in the nanocomposites acted as an adsorbent-buffer, which favored the medium pH in-addition to the stimulatory effects of Fe3O4 NPs. Cell growth and specific hydrogenase activity analysis were also performed to supplement the hydrogen production results. Gompertz and modified Logistic kinetic models were employed for kinetic modeling of experimental hydrogen production values. The Fe3O4/DSAC nanocomposites exhibited significant application potential for the production of biohydrogen from date fruit wastes.

Renewable biogas production technology is an excellent method for eradication of greenhouse gas emission and thereby reducing global warming. This review discusses extensively on global biomass potential, energy need and method of satisfying the energy demand through sustainable techniques. One of the best alternative technological developments for the conversion of waste into useful energy is anaerobic digestion to produce biogas. It is recognized as one among leading green energy to manage the environmental and meet the current energy tasks to tackle globally. Generally, biogas can be utilized for cooking, heat and electricity generation. In order to extend the scope of application, traces of carbon dioxide, hydrogen sulphide has to be removed by several upgrading technologies to produce high purity methane (90%). This study discusses on biogas up-gradation using physical and chemical absorption, membrane separation, cryogenic separation, hybrid technology etc. Among the various up-gradation techniques, hybrid technology yields methane purity of 97%. In addition, this work reviews about benefits and problems in anaerobic integrated Solid Oxide Fuel Cell (SOFC) with latest real-world achievement in SOFC. Several SOFC systems with dynamic model development were reviewed based on efficiency of power generation. SOFC generates 45% more electricity than generator with heat engine. This review extends the scope for further research in biogas upgradation and global warming mitigation potential with carbon credits.

Sweetening units using methyl diethanolamine (MDEA) solvent are instrumental in removing hydrogen sulfide and carbon dioxide from natural gas. However, over time MDEA degrades and loses its scaveng...

To reach the emission limits imposed by governments and reduce the negative impact on the environment, the use of aftertreatment systems has become essential for internal combustion engine (ICE) based powertrains. In particular, the selective catalytic reduction (SCR) system is a widespread aftertreatment technology with high efficiency for [Formula: see text] abatement which shows complex dynamics and requires urea injection as reducing agent. Current urea injection strategies usually rely on the [Formula: see text] emissions feedback. This work presents a model for the on-line simultaneous prediction of [Formula: see text] and [Formula: see text] emissions after the SCR catalyst, allowing the emissions estimation even in conditions of urea injector failure, when it is not possible to rely on the injector feedback signal. The proposed model is based on state of the art on-board after-treatment instrumentation and proposes an extended Kalman filter (EKF) to combine a data-based model and the analysis of sensor signals to provide a reliable estimation of [Formula: see text] and [Formula: see text] slip. The proposed strategy is experimentally assessed in dynamic driving cycles, such as Worldwide harmonised Light vehicles Test Cycle (WLTC) and Standardised Random Test (RTS). The proposed method is evaluated in standard conditions (without failures) and with urea injection failures of 25% and 120% of the nominal injection amount. As a result, the prediction on [Formula: see text] and [Formula: see text] slip has been improved in all injection failure conditions, by an overall average of 47.8% and 61.8%, respectively, when compared to state-of-the-art control oriented models (physically based zero dimensional model or data-based).

International audience; Pectin, the major non-cellulosic component of primary cell wall can be degraded by polygalacturonases (PGs) and pectin methylesterases (PMEs) during pathogen attack on plants. We characterized two novel enzymes,VdPG2 and VdPME1, from the fungal plant pathogen Verticillium dahliae. VdPME1 was most active on citrus methylesterified pectin (55–70%) at pH 6 and a temperature of 40 °C, while VdPG2 was most active on polygalacturonic acid at pH 5 and a temperature of 50 °C. Using LC-MS/MS oligo profiling, and various pectins,the mode of action of VdPME1 and VdPG2 were determined. VdPME1 was shown to be processive, in accordance with the electrostatic potential of the enzyme. VdPG2 was identified asendo-PG releasing both methylesterified and non-methylesterified oligogalacturonides (OGs). Additionally, whenflax roots were used as substrate, acet-ylated OGs were detected. The comparisons of OGs released from Verticillium-susceptible and partially resistant flax cultivars identified new possible elicitor of plant defence responses.

[Background]: The dynamics of the actomyosin machinery is at the core of many important biological processes. Several relevant cellular responses such as the rhythmic compression of the cell cortex are governed, at a mesoscopic level, by the nonlinear interaction between actin monomers, actin crosslinkers, and myosin motors. Coarse-grained models are an optimal tool to study actomyosin systems, since they can include processes that occur at long time and space scales, while maintaining the most relevant features of the molecular interactions. [Results]: Here, we present a coarse-grained model of a two-dimensional actomyosin cortex, adjacent to a three-dimensional cytoplasm. Our simplified model incorporates only well-characterized interactions between actin monomers, actin crosslinkers and myosin, and it is able to reproduce many of the most important aspects of actin filament and actomyosin network formation, such as dynamics of polymerization and depolymerization, treadmilling, network formation, and the autonomous oscillatory dynamics of actomyosin. [Conclusions]: We believe that the present model can be used to study the in vivo response of actomyosin networks to changes in key parameters of the system, such as alterations in the attachment of actin filaments to the cell cortex., DGM acknowledges funding from the Spanish Ministerio de Econoíma y Competitividad (BFU2014-53299-P, RTI2018-096953-B-I00). PCF acknowledges funding from IFIMAC-UAM, through the “María de Maeztu” Programme for Units of Excellence in R&D from the Spanish Ministerio de Economía y Competitividad (CEX2018-000805-M). ALI acknowledges funding from Comunidad de Madrid (PEJD-2018- PRE/BMD-7980). Institutional grants by Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2018-000805-M).

Computer-assistance allows selecting the most adequate low-cost organic structure directing agents (OSDAs) for the crystallization of Al-rich CHA-type zeolites. The host-guest stabilization energies of tetraethylammonium (TEA), methyltriethylammonium (MTEA) and dimethyldiethylammonium (DMDEA), in combination with Na, were first theoretically evaluated. This “ab-initio” analysis reveals that two TEA show a serious steric hindrance in a cha cavity, whereas two MTEA would present excellent host-guest confinements. The synthesis of Al-rich CHA-type zeolites has been accomplished using TEA and MTEA. Electron diffraction and high-resolution transmission electron microscopy reveal large CHA-domains with narrow faulted GME-domains in the CHA-type material synthesized with TEA, confirming the better OSDA-directing roles of MTEA cations towards the cha cavity, in good agreement with DFT calculations. Cu-exchanged Al-rich CHA-type samples achieved with MTEA and TEA show excellent catalytic activity and hydrothermal stability for the selective catalytic reduction (SCR) of NOx with ammonia under conditions relevant for future heavy duty diesel conditions., This work has been supported by Umicore and by the Spanish Government-MCIU through RTI2018-101033-B-I00 (MCIU/AEI/FEDER, UE) and PID2020-112590GB-C21 (AEI/FEDER, UE). T.W. acknowledges financial support by the Swedish Research Council (Grant No. 2019-05465). E.B. acknowledges the Spanish Government-MCIU for a FPI scholarship (PRE2019-088360). P.F. thanks ITQ for a contract. The Electron Microscopy Service of the UPV is acknowledged for their help in sample characterization. The computations were performed on the Tirant III cluster of the Servei d'Informàtica of the University of Valencia.

In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet-Spengler cyclization on steroid-derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase-independent cell-death mechanism, an appealing feature when new antitumor compounds are searched.

Gaining an in-depth understanding of the response of Saccharomyces cerevisiae to the different inhibitors generated during the pretreatment of lignocellulosic material is driving the development of new strains with higher inhibitor tolerances. The objective of this study is to assess, using flow cytometry, how three common inhibitors (vanillin, furfural, and acetic acid) affect the membrane potential, the membrane permeability and the concentration of reactive oxygen species (ROS) during the different fermentations. The membrane potential decreased during the detoxification phase and reflected on the different mechanisms of the toxicity of the inhibitors. While vanillin and furfural caused a metabolic inhibition and a gradual depolarization, acetic acid toxicity was related to fast acidification of the cytosol, causing an immediate depolarization. In the absence of acetic acid, ethanol increased membrane permeability, indicating a possible acquired tolerance to ethanol due to an adaptive response to acetic acid. The intracellular ROS concentration also increased in the presence of the inhibitors, indicating oxidative stress. Measuring these features with flow cytometry allows a real-time assessment of the stress of a cell culture, which can be used in the development of new yeast strains and to design new propagation strategies to pre-adapt the cell cultures to the inhibitors.

HO radicals are the most important reactive species generated during water treatment by non-thermal plasma devices. In this letter, we report the first quantification of the steady-state concentration and lifetime of plasma-produced hydroxyl radicals in water solutions at pH 3 and 7, and we discuss the differences based on their reactivity with other plasma-generated species. Finally, we show to what extent the use of chemical probes to quantify short-lived reactive species has an influence on the results and that it should be taken into account.

Biodiesel is an alternative to fossil fuels for diesel engines, yet actual biofuel properties need to be tuned to comply with fuel standards. In particular, fuel stability is required for efficiency and commercial use. Fuel stability varies with the nature and proportion of chemical functional groups of biodiesel. Optimum oxidation stability is required because degradation by oxidation gives products that compromise fuel properties and impair fuel quality and engine performance. For instance, oxidation induces the formation of short-chain corrosive acids and deposits. Here, we review techniques to improve the oxidation stability of biodiesel. For instance, stability is improved by additives such as antioxidants. Factors influencing oxidation stability include composition of fatty acids, acid content, peroxide content, iodine content, viscosity, insoluble impurities, external conditions, and storage material. Antioxidants reduce lipid peroxidation at the beginning of the chain reaction and increase the onset temperatures.

Altres ajuts: CERCA Programme/Generalitat de Catalunya, Fundaluce and "la Caixa" foundations (ID 100010434, agreement LCF/PR/HR19/52160010), Co-financed by the European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014-2020 Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice.

In the present study, ozone was introduced as an alternative approach to harvest and disrupt microalgae cells (Chlorella vulgaris) simultaneously for biodiesel production. At the optimum ozonation conditions (6.14 g·h−1 ozone concentration, 30 min ozonation time, 1 L·min−1 of ozone flowrate at medium pH of 10 and temperature of 30 °C), the sedimentation efficiency of microalgae cells increased significantly from 12.56% to 68.62%. It was observed that the microalgae cells aggregated to form flocs after pretreated with ozone due to the increment of surface charge from −20 to −6.59 mV. Besides, ozone had successfully disrupted the microalgae cells and resulted in efficient lipid extraction, which was 1.9 times higher than the control sample. The extracted microalgae lipid was mainly consisted of methyl palmitate (C16:0), methyl oleate (C18:1) and methyl linolenate (C18:3), making it suitable for biodiesel production. Finally, utilization of recycled culture media after ozonation pre-treatment showed robust growth of microalgae, in which the biomass yield was maintained in the range of 0.796 to 0.879 g ·h−1 for 5 cycles of cultivation.

The use of oxidative stress generated by Cold Atmospheric Plasma (CAP) in oncology is being recently studied as a novel potential anti-cancer therapy. However, the beneficial effects of CAP for treating osteosarcoma have mostly been demonstrated in 2-dimensional cultures of cells, which do not mimic the complexity of the 3-dimensional (3D) bone microenvironment. In order to evaluate the effects of CAP in a relevant context of the human disease, we developed a 3D tissue-engineered model of osteosarcoma using a bone-like scaffold made of collagen type I and hydroxyapatite nanoparticles. Human osteosarcoma cells cultured within the scaffold showed a high capacity to infiltrate and proliferate and to exhibit osteomimicry in vitro. As expected, we observed significantly different functional behaviors between monolayer and 3D cultures when treated with Cold Plasma-Activated Ringer's Solution (PAR). Our data reveal that the 3D environment not only protects cells from PAR-induced lethality by scavenging and diminishing the amount of reactive oxygen and nitrogen species generated by CAP, but also favours the stemness phenotype of osteosarcoma cells. This is the first study that demonstrates the negative effect of PAR on cancer stem-like cell subpopulations in a 3D biomimetic model of cancer. These findings will allow to suitably re-focus research on plasma-based therapies in future., Graphical abstract Image 1, Highlights • Tissue-engineered 3D osteosarcoma model exhibits osteomimicry in vitro. • 3D microenvironment scavenges RONS diminishing lethality of Plasma-Activated Ringer. • Expression of RONS-protective genes in the tumor model diminishes sensitivity to PAR. • Cancer Stem-Like Cell properties are enhanced in 3D following PAR treatment. • PAR treatment of OS in the microenvironment favoring adaptation to oxidative stress.

Graphical abstract, SMAD transcription factors, the main effectors of the TGFβ (transforming growth factor β) network, have a mixed architecture of globular domains and flexible linkers. Such a complicated architecture precluded the description of their full-length (FL) structure for many years. In this study, we unravel the structures of SMAD4 and SMAD2 proteins through an integrative approach combining Small-angle X-ray scattering, Nuclear Magnetic Resonance spectroscopy, X-ray, and computational modeling. We show that both proteins populate ensembles of conformations, with the globular domains tethered by disordered and flexible linkers, which defines a new dimension of regulation. The flexibility of the linkers facilitates DNA and protein binding and modulates the protein structure. Yet, SMAD4FL is monomeric, whereas SMAD2FL is in different monomer–dimer-trimer states, driven by interactions of the MH2 domains. Dimers are present regardless of the SMAD2FL activation state and concentration. Finally, we propose that SMAD2FL dimers are key building blocks for the quaternary structures of SMAD complexes.

Contains fulltext : 235283.pdf (Publisher’s version ) (Open Access) Background: The 29th EADV Virtual Congress took place between the 29th-31st of October 2020. On October 29th, there was a Session on systemic treatment in which Professors Ulrich Mrowietz and Mar Llamas-Velasco presented the latest research on the efficacy of dimethyl fumarate (DMF) treatment for moderate-to-severe plaque psoriasis (BRIDGE and DIMESKIN 1 studies, respectively). The accepted DMF abstract from Professor Matthias Augustin, on the SKILL study, is also presented here. Results: Data from either prospective interventional (BRIDGE) or non-interventional (DIMESKIN 1, SKILL) studies among patients with moderate-to-severe psoriasis showed that DMF provides a positive efficacy profile in all four body regions included in the Psoriasis Area and Severity Index assessment (head and neck, trunk, upper and lower extremities) and a particularly interesting profile (strong efficacy) in the head and neck region. These findings may be of special interest to patients with scalp psoriasis who have been using topical therapies for a long time. Patient-reported outcomes (quality of life, pruritus) also improved during the 24 weeks of DMF treatment. The safety profile of DMF was similar to the previously described with fumaric acid esters. Conclusions: In summary, these results confirm the favorable efficacy and safety profile of DMF in long-term treatment.