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Abstract Cobalt is an efficient catalyst for Fischer−Tropsch synthesis (FTS) of hydrocarbons from syngas (CO + H2) with enhanced selectivity for long-chain hydrocarbons when promoted by Manganese. However, the molecular scale origin of the enhancement remains unclear. Here we present an experimental and theoretical study using model catalysts consisting of crystalline CoMnOx nanoparticles and thin films, where Co and Mn are mixed at the sub-nm scale. Employing TEM and in-situ X-ray spectroscopies (XRD, APXPS, and XAS), we determine the catalyst’s atomic structure, chemical state, reactive species, and their evolution under FTS conditions. We show the concentration of CHx, the key intermediates, increases rapidly on CoMnOx, while no increase occurs without Mn. DFT simulations reveal that basic O sites in CoMnOx bind hydrogen atoms resulting from H2 dissociation on Co0 sites, making them less available to react with CHx intermediates, thus hindering chain termination reactions, which promotes the formation of long-chain hydrocarbons.

Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.

El sistema de justicia juvenil está mostrando cambios en sus enfoques y principios. El objetivo de esta investigación es identificar qué efectos surgen cuando se trabaja de manera interdisciplinaria, situando a los menores no como infractores, sino como adolescentes, reconociendo sus necesidades, capacidades y derechos. A partir de un enfoque cualitativo, se diseña un estudio de caso. Se eligen tres individuos entre el alumnado de un instituto de enseñanza secundaria donde se llevan a cabo medidas de internamiento. Mediante entrevistas, análisis documental y observación participante, se analizan las historias de vida, el acompañamiento de las familias y el trabajo realizado por los miembros del equipo docente en la identificación y eliminación de las barreras. Los resultados ponen de manifiesto la necesidad de partir de las vivencias de cada adolescente para identificar las barreras que encuentra. Se concluye que cuando se detectan las barreras y se trabaja en ellas se promueve el trabajo en red, la compartición de responsabilidades, la cohesión de criterios y el compromiso institucional.

Abstract Electrochemical CO2 reduction reaction in aqueous electrolytes is a promising route to produce added-value chemicals and decrease carbon emissions. However, even in Gas-Diffusion Electrode devices, low aqueous CO2 solubility limits catalysis rate and selectivity. Here, we demonstrate that when assembled over a heterogeneous electrocatalyst, a film of nitrile-modified Metal-Organic Framework (MOF) acts as a remarkable CO2-solvation layer that increases its local concentration by ~27-fold compared to bulk electrolyte, reaching 0.82 M. When mounted on a Bi catalyst in a Gas Diffusion Electrode, the MOF drastically improves CO2-to-HCOOH conversion, reaching above 90% selectivity and partial HCOOH currents of 166 mA/cm2 (at −0.9 V vs RHE). The MOF also facilitates catalysis through stabilization of reaction intermediates, as identified by operando infrared spectroscopy and Density Functional Theory. Hence, the presented strategy provides new molecular means to enhance heterogeneous electrochemical CO2 reduction reaction, leading it closer to the requirements for practical implementation.

Abstract Metal promotion could unlock high performance in zinc-zirconium catalysts, ZnZrO x , for CO2 hydrogenation to methanol. Still, with most efforts devoted to costly palladium, the optimal metal choice and necessary atomic-level architecture remain unclear. Herein, we investigate the promotion of ZnZrO x catalysts with small amounts (0.5 mol%) of diverse hydrogenation metals (Re, Co, Au, Ni, Rh, Ag, Ir, Ru, Pt, Pd, and Cu) prepared via a standardized flame spray pyrolysis approach. Cu emerges as the most effective promoter, doubling methanol productivity. Operando X-ray absorption, infrared, and electron paramagnetic resonance spectroscopic analyses and density functional theory simulations reveal that Cu0 species form Zn-rich low-nuclearity CuZn clusters on the ZrO2 surface during reaction, which correlates with the generation of oxygen vacancies in their vicinity. Mechanistic studies demonstrate that this catalytic ensemble promotes the rapid hydrogenation of intermediate formate into methanol while effectively suppressing CO production, showcasing the potential of low-nuclearity metal ensembles in CO2-based methanol synthesis.

Abstract Vaccines based on mRNA technology have revolutionized the field. In fact, lipid nanoparticles (LNP) formulated with mRNA are the preferential vaccine platform used in the fight against SARS-CoV-2 infection, with wider application against other diseases. The high demand and property right protection of the most potent cationic/ionizable lipids used for LNP formulation of COVID-19 mRNA vaccines have promoted the design of alternative nanocarriers for nucleic acid delivery. In this study we have evaluated the immunogenicity and efficacy of different rationally designed lipid and polymeric-based nanoparticle prototypes against SARS-CoV-2 infection. An mRNA coding for a trimeric soluble form of the receptor binding domain (RBD) of the spike (S) protein from SARS-CoV-2 was encapsulated using different components to form nanoemulsions (NE), nanocapsules (NC) and lipid nanoparticles (LNP). The toxicity and biological activity of these prototypes were evaluated in cultured cells after transfection and in mice following homologous prime/boost immunization. Our findings reveal good levels of RBD protein expression with most of the formulations. In C57BL/6 mice immunized intramuscularly with two doses of formulated RBD-mRNA, the modified lipid nanoparticle (mLNP) and the classical lipid nanoparticle (LNP-1) were the most effective delivery nanocarriers at inducing binding and neutralizing antibodies against SARS-CoV-2. Both prototypes fully protected susceptible K18-hACE2 transgenic mice from morbidity and mortality following a SARS-CoV-2 challenge. These results highlight that modulation of mRNAs immunogenicity can be achieved by using alternative nanocarriers and support further assessment of mLNP and LNP-1 prototypes as delivery vehicles for mRNA vaccines.

Abstract For decarbonization of ammonia production in industry, alternative methods by exploiting renewable energy sources have recently been explored. Nonetheless, they still lack yield and efficiency to be industrially relevant. Here, we demonstrate an advanced approach of nitrogen fixation to synthesize ammonia at ambient conditions via laser–induced multiphoton dissociation of lithium oxide. Lithium oxide is dissociated under non–equilibrium multiphoton absorption and high temperatures under focused infrared light, and the generated zero–valent metal spontaneously fixes nitrogen and forms a lithium nitride, which upon subsequent hydrolysis generates ammonia. The highest ammonia yield rate of 30.9 micromoles per second per square centimeter is achieved at 25 °C and 1.0 bar nitrogen. This is two orders of magnitude higher than state–of–the–art ammonia synthesis at ambient conditions. The focused infrared light here is produced by a commercial simple CO2 laser, serving as a demonstration of potentially solar pumped lasers for nitrogen fixation and other high excitation chemistry. We anticipate such laser-involved technology will bring unprecedented opportunities to realize not only local ammonia production but also other new chemistries .

Abstract Carbon supports are ubiquitous components of heterogeneous catalysts for acetylene hydrochlorination to vinyl chloride, from commercial mercury-based systems to more sustainable metal single-atom alternatives. Their potential co-catalytic role has long been postulated but never unequivocally demonstrated. Herein, we evidence the bifunctionality of carbons and metal sites in the acetylene hydrochlorination catalytic cycle. Combining operando X-ray absorption spectroscopy with other spectroscopic and kinetic analyses, we monitor the structure of single metal atoms (Pt, Au, Ru) and carbon supports (activated, non-activated, and nitrogen-doped) from catalyst synthesis, using various procedures, to operation at different conditions. Metal atoms exclusively activate hydrogen chloride, while metal-neighboring sites in the support bind acetylene. Resolving the coordination environment of working metal atoms guides theoretical simulations in proposing potential binding sites for acetylene in the support and a viable reaction profile. Expanding from single-atom to ensemble catalysis, these results reinforce the importance of optimizing both metal and support components to leverage the distinct functions of each for advancing catalyst design.

We present the first comprehensive investigation of transition metal-substituted Hydroxyapatite (TM-HAP) materials for photocatalytic CO2 reduction (CO2RR). Density functional theory (DFT) was used to study in a systematic manner the stability of 3d, 4d, 5d transition metal dopants on the HAP (000̅1) surface, analyzing their stability, activity, and selectivity for photocatalytic CO2RR. DFT results allowed to narrow down the selection to three transition metal elements (Co, Ni, Mo) based on their structural stability, band structure and performance. A selective analysis of product formation for carbon monoxide and formate was made, showing that TM dopants facilitate the initial protonation step in the CO2 reduction by adsorbing H2 molecule on TM atoms and then dissociating it into two hydrogen atoms. The performance of Ni- and Co-HAP towards the reaction activity is consistent with experimental results. Mo-HAP stands as a new and attractive photocatalyst for further investigation, given its excellent predicted performance.

Abstract Ceria-based single-atom catalysts present complex electronic structures due to the dynamic electron transfer between the metal atoms and the semiconductor oxide support. Understanding these materials implies retrieving all states in these electronic ensembles, which can be limiting if done via density functional theory. Here, we propose a data-driven approach to obtain a parsimonious model identifying the appearance of dynamic charge transfer for the single atoms (SAs). We first constructed a database of (701) electronic configurations for the group 9–11 metals on CeO2(100). Feature Selection based on predictive Elastic Net and Random Forest models highlights eight fundamental variables: atomic number, ionization potential, size, and metal coordination, metal–oxygen bond strengths, surface strain, and Coulomb interactions. With these variables a Bayesian algorithm yields an expression for the adsorption energies of SAs in ground and low-lying excited states. Our work paves the way towards understanding electronic structure complexity in metal/oxide interfaces.

The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine.

Background: This work studied the use of the organic fertilizers DTPA-Fe and EDDS-Fe as iron chelates for solar driven photo-Fenton process at natural pH. This process was proposed to investigate its performance on removing a mixture of agrochemicals (propiconazole, imidacloprid and diuron) from pineapple processing wastewater to obtain a suitable effluent to be reused in the agricultural sector. Methods: Experiments were carried out in a solar simulator with a stirred cylindric photoreactor, with a volume of 150 mL and controlled temperature (20°C). The first set of experiments was carried out with ultrapure water to determine optimal iron and H2O2 concentrations. The second was performed with simulated wastewater of pineapple processing. Results: The optimized operational conditions for both iron complexes were 10 mg L-1 of Fe (III) and 25 mg L-1 of H2O2, since more than 80% of micropollutants (MP) (at an initial concentration of 1 mg L-1 of each compound) were removed in only 20 min with both DTPA-Fe and EDDS-Fe. The effect of organic matter and inorganic salts on radicals scavenging and chelates stability was also investigated in the experiments performed with synthetic pineapple processing wastewater. The results disclosed differences depending on the iron complex. Nitrites were the principal component influencing the tests carried out with EDDS-Fe. While carbonates at low concentration only significantly affected the experiments performed with DTPA-Fe, they were the major influence on the MPs removal efficiency decrease. In contrast, the presence of Ca2+ and Mg2+ only influence on this last one. Finally, the results of phytotoxicity disclosed the suitability of treated effluent to be reused in the agricultural sector. Conclusions: This work demonstrated that solar powered photo-Fenton catalysed by iron fertilizer EDDS is a suitable technology for depolluting water streams coming from pineapple processing plants at circumneutral pH, and its subsequent reuse for crop irrigation.

Palladium-promoted indium oxide is a catalyst with potential to realize the large-scale conversion of CO2 into the commodity methanol. This work focuses on the low-cost nickel as an alternative appealing promoter, revealing the atomic-level catalyst design unlocking maximal selectivity and activity.

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson’s disease patients (Parkinson’s Holter). The effectiveness of these monitoring devices for improving clinical control is not known.Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson’s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months.The primary outcome is the efficiency of the Parkinson’s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor–patient contacts will be analysed. The noninferiority of the Parkinson’s Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective.Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson’s Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Trial registration NCT04176302; https://clinicaltrials.gov/show/NCT04176302

Assessing catalytic mechanisms using DFT calculations greatly aids catalyst design, but is impractical for large molecules. Here the authors develop a statistical learning-based thermochemical model for estimating adsorption of organics onto metals, retaining DFT accuracy while reducing the number of calculations by a factor of 20.

Generating and quantifying the effect of the promoter speciation in heterogeneous catalysts is very challenging. Here, the authors show that the precise palladium atoms architecture reached by controlled co-precipitation overcomes selectivity and stability limitations associated with palladium nanoparticles for CO2-based methanol synthesis.

The search for robust heterogeneous catalysts for the production of linear α-olefins is still a challenge as they do not show well-defined sites and lack the high selectivity reported for homogeneous counterparts. Here the authors show how the precise engineering of metal–organic frameworks (MOFs) holds promise for a sustainable process.

Developing robust catalysts for alkyne semi-hydrogenation remains a challenge. Here, the authors introduce a scalable protocol to prepare crystal phase and orientation controlled Pd3S nanoparticles supported on carbon nitride, exhibiting unparalleled semi-hydrogenation performance due to a high density of active and selective ensembles.

The production of hydrogen from biomass is of fundamental importance for a sustainable future. Here, the authors present a multiscale method that allows the formulation of scaling relationships and microkinetics of C1-C2 alcohol decomposition based on a density functional theory open database.

The importance of microRNAs in the regulation of various aspects of biology and disease is well recognized. However, what remains largely unappreciated is that a significant number of miRNAs are embedded within and are often co-expressed with protein-coding host genes. Such a configuration raises the possibility of a functional interaction between a miRNA and the gene it resides in. This is exemplified by the Drosophila melanogaster dE2f1 gene that harbors two miRNAs, mir-11 and mir-998, within its last intron. miR-11 was demonstrated to limit the proapoptotic function of dE2F1 by repressing cell death genes that are directly regulated by dE2F1, however the biological role of miR-998 was unknown. Here we show that one of the functions of miR-998 is to suppress dE2F1-dependent cell death specifically in rbf mutants by elevating EGFR signaling. Mechanistically, miR-998 operates by repressing dCbl, a negative regulator of EGFR signaling. Significantly, dCbl is a critical target of miR-998 since dCbl phenocopies the effects of miR-998 on dE2f1-dependent apoptosis in rbf mutants. Importantly, this regulation is conserved, as the miR-998 seed family member miR-29 repressed c-Cbl, and enhanced MAPK activity and wound healing in mammalian cells. Therefore, the two intronic miRNAs embedded in the dE2f1 gene limit the apoptotic function of dE2f1, but operate in different contexts and act through distinct mechanisms. These results also illustrate that examining an intronic miRNA in the context of its host's function can be valuable in elucidating the biological function of the miRNA, and provide new information about the regulation of the host gene itself.

Deafness is a complex disorder affecting 1/1000 infants. In developed countries, more than 50% of deafness cases are thought to have a genetic cause. At least 40 loci for dominant non-syndromic deafness and another 30 for recessive non-syndromic deafness have been described. Mutations in the GJB2 gene are the cause of an important number of cases of non-syndromic recessive deafness but are not as common in non-syndromic dominant deafness cases. We describe here a new dominant mutation (G21R) in the GJB2 gene which causes deafness and has been identified in a three generation Cuban family with dominant non-syndromic congenital sensorineural profound deafness.

B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell-specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes.

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.

Gene expression profiling has identified cancer prognostic and predictive signatures with superior performance to conventional histopathological or clinical parameters. Consequently, signatures are being incorporated into clinical practice and will soon influence everyday decisions in oncology. However, the slight overlap in the gene identity between signatures for the same cancer type or condition raises questions about their biological and clinical implications. To clarify these issues, better understanding of the molecular properties and possible interactions underlying apparently dissimilar signatures is needed. Here, we evaluated whether the signatures of 24 independent studies are related at the genome, transcriptome or proteome levels. Significant associations were consistently observed across these molecular layers, which suggest the existence of a common cancer cell phenotype. Convergence on cell proliferation and death supports the pivotal involvement of these processes in prognosis, metastasis and treatment response. In addition, functional and molecular associations were identified with the immune response in different cancer types and conditions that complement the contribution of cell proliferation and death. Examination of additional, independent, cancer datasets corroborated our observations. This study proposes a comprehensive strategy for interpreting cancer signatures that reveals common design principles and systems-level properties.