Platinum is a prominent catalyst for a multiplicity of reactions because of its high activity and stability. As Pt nanoparticles are normally used to maximize catalyst utilization and to minimize ...catalyst loading, it is important to rationalize and predict catalytic activity trends in nanoparticles in simple terms, while being able to compare these trends with those of extended surfaces. The trends in the adsorption energies of small oxygen‐ and hydrogen‐containing adsorbates on Pt nanoparticles of various sizes and on extended surfaces were analyzed through DFT calculations by making use of the generalized coordination numbers of the surface sites. This simple and predictive descriptor links the geometric arrangement of a surface to its adsorption properties. It generates linear adsorption‐energy trends, captures finite‐size effects, and provides more accurate descriptions than d‐band centers and usual coordination numbers. Unlike electronic‐structure descriptors, which require knowledge of the densities of states, it is calculated manually. Finally, it was shown that an approximate equivalence exists between generalized coordination numbers and d‐band centers.
The trends in the adsorption energies of oxygen‐ and hydrogen‐containing adsorbates on various platinum nanoparticles and extended surfaces are analyzed. By means of generalized coordination numbers, it is possible to unify the trends among dissimilar structures and sizes. Adsorption energies for terraces, edges, corners, and adatoms and finite‐size effects could be accurately described.
No prospective trials have been carried out comparing antibiotic treatment alone with primarily surgical treatment in patients with diabetes and foot osteomyelitis. The aim of the current study was ...to compare the outcomes of the treatment of diabetic foot osteomyelitis in patients treated exclusively with antibiotics versus patients who underwent conservative surgery, following up the patients for a period of 12 weeks after healing.
Between 1 January 2010 and 31 December 2012, a prospective randomized comparative trial (clinical trial reg. no. NCT01137903, clinicaltrials.gov) of patients with diabetes who had received a diagnosis of neuropathic foot ulcers complicated by osteomyelitis was carried out at the Diabetic Foot Unit at the Complutense University of Madrid. Patients were randomized into the following two groups: the antibiotics group (AG) and the surgical group (SG). Antibiotics were given for a period of 90 days in the AG. Patients in the SG received conservative surgery with postoperative antibiotic treatment for 10 days.
Eighteen patients (75%) achieved primary healing in the AG, and 19 (86.3%) in the SG (P = 0.33). The median time to healing was 7 weeks (quartile Q 1 to Q5, Q3-Q8) in the AG and 6 weeks (Q1-Q3, Q3-Q9) in the SG (P = 0.72). The conditions of four patients from the AG worsened (16.6%), and they underwent surgery. Three patients from the SG required reoperation. No difference was found between the two groups regarding minor amputations (P = 0.336).
Antibiotic therapy and surgical treatment had similar outcomes in terms of healing rates, time to healing, and short-term complications in patients with neuropathic forefoot ulcers complicated by osteomyelitis without ischemia or necrotizing soft tissue infections.
Tomato (Solanum lycopersicum L.) fruit-set and growth depend on gibberellins (GAs). Auxins, another kind of hormone, can also induce parthenocarpic fruit growth in tomato, although their possible ...interaction with GAs is unknown. We showed that fruit development induced by the auxins indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid (2,4-D) were significantly reduced by the simultaneous application of inhibitors of GA biosynthesis, and that this effect was reversed by the application of GA₃. This suggested that the effect of auxin was mediated by GA. Parthenocarpic fruits induced by 2,4-D had higher levels of the active GA₁, its precursors and metabolites, than unpollinated non-treated ovaries, but similar levels as those found in pollinated ovaries. Application experiments of radioactive-labelled GAs to unpollinated ovaries showed than 2,4-D altered GA metabolism (both biosynthesis and catabolism) in vivo. Transcript levels of genes encoding copalyldiphosphate synthase (SlCPS), SlGA20ox1, SlGA20ox2 and SlGA20ox3, and SlGA3ox1 were higher in unpollinated ovaries treated with 2,4-D. In contrast, transcript levels of SlGA2ox2 (out of the five SlGA2ox genes known to encode this kind of GA-inactivating enzyme) were lower in ovaries treated with 2,4-D. Our results support the idea that auxins induce fruit-set and growth in tomato, at least partially, by enhancing GA biosynthesis (GA 20-oxidase, GA 3-oxidase and CPS), and probably by decreasing GA inactivation (GA2ox2) activity, thereby leading to higher levels of GA₁. The expression of diverse Aux/indole-3-acetic acid (IAA) and auxin response factors, which may be involved in this effect of auxin, was also altered in 2,4-D-induced ovaries.
A coordination polymer is fully exfoliated by solvent‐assisted interaction only. The soft‐delamination process results from the structure of the starting material, which shows a layered structure ...with weak layer‐to‐layer interactions and cavities with the ability to locate several solvents in an unselective way. These results represent a significant step forward towards the production of structurally designed one‐molecule thick 2D materials with tailored physico‐chemical properties.
Ceftazidime-avibactam is a combination of β-lactam/β-lactamase inhibitor, the use of which is restricted to some clinical cases, including cystic fibrosis patients infected with multidrug-resistant
, ...in which mutation is the main driver of resistance. This study aims to predict the mechanisms of mutation-driven resistance that are selected for when
is challenged with either ceftazidime or ceftazidime-avibactam. For this purpose,
PA14 was submitted to experimental evolution in the absence of antibiotics and in the presence of increasing concentrations of ceftazidime or ceftazidime-avibactam for 30 consecutive days. Final populations were analyzed by whole-genome sequencing. All evolved populations reached similar levels of ceftazidime resistance. In addition, they were more susceptible to amikacin and produced pyomelanin. A first event in this evolution was the selection of large chromosomal deletions containing
(involved in pyomelanin production),
(involved in β-lactams resistance), and
(involved in aminoglycoside resistance). Besides mutations in
and
that regulate β-lactamase expression, mutations related to MexAB-OprM overexpression were prevalent. Ceftazidime-avibactam challenge selected mutants in the putative efflux pump
and
and in a two-component system (
and
), likely regulating its expression. All populations produced pyomelanin and were more susceptible to aminoglycosides, likely due to the selection of large chromosomal deletions. Since pyomelanin-producing mutants presenting similar deletions are regularly isolated from infections, the potential aminoglycoside hypersusceptiblity and reduced β-lactam susceptibility of pyomelanin-producing
should be taken into consideration for treating infections caused by these isolates.
Summary
Obesity‐related glomerulopathy (ORG) is a silent comorbidity which is increasing in incidence as the obesity epidemic escalates. ORG is associated with serious health consequences including ...chronic kidney disease, end‐stage renal disease (ESRD), and increased mortality. Although the pathogenic mechanisms involved in the development of ORG are not fully understood, glomerular hemodynamic changes, renin‐angiotensin‐aldosterone system (RAAS) overactivation, insulin‐resistance, inflammation and ectopic lipid accumulation seem to play a major role. Despite albuminuria being commonly used for the non‐invasive evaluation of ORG, promising biomarkers of early kidney injury that are emerging, as well as new approaches with proteomics and metabolomics, might permit an earlier diagnosis of this disease. In addition, the assessment of ectopic kidney fat by renal imaging could be a useful tool to detect and evaluate the progression of ORG. Weight loss interventions appear to be effective in ORG, although large‐scale trials are needed. RAAS blockade has a renoprotective effect in patients with ORG, but even so, a significant proportion of patients with ORG will eventually progress to ESRD despite therapeutic efforts. It is noteworthy that certain antidiabetic agents such as sodium‐glucose cotransporter 2 inhibitors (SGLT2i) or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) could be useful in the treatment of ORG through different pleiotropic effects. In this article, we review current approaches and future perspectives in the care and treatment of ORG.
Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the ...characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia.
A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared.
Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group.
MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.
The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5′ → 3′ exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes ...major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C‐terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as “cotranslational mRNA decay.” The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5′ → 3′ decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C‐terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C‐terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.
cRat1 can partially restore the cell volume, mRNA stability, proliferation rate, and 5′ → 3′ decay alterations that characterize xrn1Δ cells. In particular, cRat1 is not a good substitute for Xrn1, for not only initiating 5′ → 3′ decay but also for following the ribosome position during cotranslational mRNA decay. The use of the AlphaFold prediction of a cRat1–ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. It seems that the two paralogs acquire specific features to make functional partitioning beneficial.
Take‐away
Cytoplasmic Rat1 partly restores the general physiological defects of an xrn1∆ mutant.
cRat1 is very inefficient in cotranslational mRNA decay.
The C‐terminal domain of Xrn1 is not involved in 5′ → 3′ cotranslational decay.
► Methanolic extracts from some edible mushrooms showed anti-inflammatory activity. ► Mushrooms extracts inhibited NO production and iNOS expression in activated macrophages. ► Mushrooms extracts ...reduced IL-1β, and IL-6 mRNA expressions in activated macrophages. ► The most effective species were
Agaricus bisporus,
Cantharellus cibarius, and
Lactarius deliciosus. ► Pyrogallol was found only in the species with anti-inflammatory activity.
Nowadays there is a great interest in the use of edible mushrooms as functional food since they are rich in bioactive compounds. Although their immunomostimulant activity has been largely demonstrated, their potential anti-inflammatory activity has been scarcely explored. We have investigated the anti-inflammatory activity of methanolic extracts from different edible mushrooms species:
Agaricus bisporus,
Boletus edulis,
Cantherellus cibarius,
Cratarellus cornucopioides,
Lactarius deliciosus and
Pleurotus ostreatus, in activated macrophages. The species that exhibited higher anti-inflammatory activities were
A. bisporus,
C. cibarius and
L. deliciosus, inducing inhibition of NO production and iNOS, IL-1β and IL6 mRNAs expression in response to LPS stimulation.
C. cornucopioides only induced inhibition of NO production and iNOS expression, and the other species did not present anti-inflammatory effects. Therefore, some edible mushrooms species have a potential anti-inflammatory capacity
in vitro, suggesting that they could be regarded as a potential source of natural anti-inflammatory agents.
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