Solvent Effects in the Homogeneous Catalytic Reduction of Propionaldehyde with Aluminium Isopropoxide Catalyst: New Insights from PFG NMR and NMR Relaxation Studies.

Solvent effects in homogeneous catalysis are known to affect catalytic activity. Whilst these effects are often described using qualitative features, such as Kamlet-Taft parameters, experimental tools able to quantify and reveal in more depth such effects have remained unexplored. In this work, PFG NMR diffusion and T1 relaxation measurements have been carried out to probe solvent effects in the homogeneous catalytic reduction of propionaldehyde to 1-propanol in the presence of aluminium isopropoxide catalyst. Using data on diffusion coefficients it was possible to estimate trends in aggregation of different solvents. The results show that solvents with a high hydrogen-bond accepting ability, such as ethers, tend to form larger aggregates, which slow down the molecular dynamics of aldehyde molecules, as also suggested by T1 measurements, and preventing their access to the catalytic sites, which results in the observed decrease of catalytic activity. Conversely, weakly interacting solvents, such as alkanes, do not lead to the formation of such aggregates, hence allowing easy access of the aldehyde molecules to the catalytic sites, resulting in higher catalytic activity. The work reported here is a clear example on how combining traditional catalyst screening in homogeneous catalysis with NMR diffusion and relaxation time measurements can lead to new physico-chemical insights into such systems by providing data able to quantify aggregation phenomena and molecular dynamics.

Creation of Al-Enriched Mesoporous ZSM-5 Nanoboxes with High Catalytic Activity: Converting Tetrahedral Extra-Framework Al into Framework Sites by Post Treatment.

ZSM-5 zeolite nanoboxes with accessible meso-micro-pore architecture and strong acid sites are important in relevant heterogeneous catalysis suffering from mass transfer limitations and weak acidities. Rational design of parent zeolites with concentrated and non-protective coordination of Al species can facilitate post-synthetic treatment to produce mesoporous ZSM-5 nanoboxes. In this work, a simple and effective method was developed to convert parent MFI zeolites with tetrahedral extra-framework Al into Al-enriched mesoporous ZSM-5 nanoboxes with low silicon-to-aluminium ratios of ≈16. The parent MFI zeolite was prepared by rapid ageing of the zeolite sol gel synthesis mixture. The accessibility to the meso-micro-porous intra-crystalline network was probed systematically by comparative pulsed field gradient nuclear magnetic resonance diffusion measurements, which, together with the strong acidity of nanoboxes, provided superb catalytic activity and longevity in hydrocarbon cracking for propylene production.

RNF187 is Downregulated Following NF-κB Inhibition in Late Erythroblasts.

Beta (ß)-thalassaemic erythroblasts grown in vitro have reduced nuclear factor kappa B (NF-κB) pathway gene expression. By inhibiting this pathway in erythroblasts from normal individuals, important downstream genes affected by this inhibition can be identified. Bay 11-7082 is a potent inhibitor of the NF-κB pathway, it acts irreversibly, inhibiting NF-κB activation by blocking tumor necrosis factor alpha (TNF-α)-induced phosphorylation of the inhibitory IκB subunit thereby preventing NF-κB activation. In this study, hematopoietic stem cells were isolated from the peripheral blood of 6 healthy individuals and were then cultured for 14 days in conditions which promote erythroid differentiation. Following erythroid lineage enrichment, these cells were stimulated with TNFα or inhibited with Bay 11-7082. Subsequent RNA isolation and gene expression analyses were performed using pooled cDNA with custom PCR arrays. Genes of interest were examined individually on non-pooled samples. Our data identified RNF187, a RING finger domain gene as being downregulated in response to NF-κB inhibition.

Differential gene expression analysis in early and late erythroid progenitor cells in ß-thalassaemia.

ß- thalassaemia is a disorder of globin gene synthesis resulting in reduced or absent production of the ß-globin chain in red blood cells. In this study, haematopoietic stem cells were isolated from the peripheral blood of six transfusion dependent ß-thalassaemia patients and six healthy controls. Following 7 and 14 d in culture, early- and late- erythroblasts were isolated and purified. No morphological difference in maturation was observed following 7 d in culture, while a delayed maturation was observed in the patient group after 14 d. Following RNA isolation and linear amplification, gene expression analyses were performed using microarray technology. The generated data were analysed by two methods: the BRB-ArrayTools platform and the Bioconductor platform using bead level data. Following 7 d culture, there was no difference in gene expression between the control and patient groups. Following 14 d culture, 384 differentially expressed genes were identified by either analysis. A subset of 90 genes was selected and the results were confirmed by Quantitative-Real-Time-polymerase chain reaction. Pathways shown to be significantly altered in the patient group include apoptosis, MAPKinase and the nuclear factor-κB pathway.

Safety of supervised trainee-performed laparoscopic surgery for inflammatory bowel disease.

PURPOSE: There is a significant risk of surgical resection during the lifetime of an inflammatory bowel disease (IBD) patient: laparoscopic surgery has been increasingly applied to the management of IBD with short and long-term advantages. The aim of this study is to demonstrate that laparoscopic surgery for IBD, performed by a surgical trainee under the supervision of an experienced trainer, is feasible and safe. METHODS: All surgical procedures were sub-divided in six critical steps in order to define the procedure as supervised trainee performed (STP) when the trainer was present unscrubbed in the theatre or assisting and trainer performed (TNER) when the trainer performed two or more critical steps of the procedure. Included were all patients undergoing laparoscopic resection for IBD between January 2009 and December 2013. Thirty-day mortality and morbidity were the primary outcomes. Reoperations and rehospitalizations within 30 days of discharge were recorded prospectively and were the secondary outcomes together with conversion rate and length of hospital stay. RESULTS: One hundred fifty-one patients were included: 77 (50.99%) STP and 74 (49.01%) TNER. No deaths occurred, and 30-day morbidity was 27.15% with no differences between the groups. Operating time was longer in the STP (166.6 ± 53.31 vs 130.4 ± 49.15). Five patients (2 vs 3) required reoperation (3.31%), while 13 patients (8.6%) required readmission. CONCLUSIONS: Laparoscopic surgery for IBD performed by a supervised trainee is safe compared to trainers performed procedures despite a longer operating time. Randomized clinical trials are needed to confirm these preliminary results and to investigate long-term outcomes.

The Effect of Nonsense Mediated Decay on Transcriptional Activity Within the Novel ß-Thalassemia Mutation HBB: c.129delT.

Premature termination codons (PTCs) are caused by mutations in the coding sequences of functional genes resulting in an incorrect assignment of a stop codon. Abnormal and truncated proteins are prevented from being translated due to the rapid degradation of mRNA carrying these mutations by an RNA surveillance mechanism referred to as nonsense mediated decay (NMD). Recently, a novel mutation in a patient from Thailand with the clinical diagnosis of Hb E (HBB: c.79G > A)/ß(0)-thalassemia (Hb E/ß(0)-thal) and whose molecular analysis demonstrated a novel mutation in the ß-globin gene, HBB: c.129delT, was reported. The result of this deletion is a frameshift (FSC) resulting in a PTC at codon 60. We have analyzed the impact of this mutation on transcription and translation of the affected ß-globin gene using an in vitro model. The quantitative real-time polymerase chain reaction (qReTi-PCR) analysis revealed that this nucleotide mutation resulted in marked mRNA degradation, which we attributed to the NMD mechanism and as such, the expected deleterious truncated HBB was not generated. This result highlights a valuable application of our in vitro gene expression model that can be used to predict possible molecular pathology for any given nucleotide mutations.

Humin Formation on SBA-15-pr-SO3H Catalysts during the Alcoholysis of Furfuryl Alcohol to Ethyl Levulinate: Effect of Pore Size on Catalyst Stability, Transport, and Adsorption.

Herein, the alcoholysis of furfuryl alcohol in a series of SBA-15-pr-SO3H catalysts with different pore sizes is reported. Elemental analysis and NMR relaxation/diffusion methods show that changes in pore size have a significant effect on catalyst activity and durability. In particular, the decrease in catalyst activity after catalyst reuse is mainly due to carbonaceous deposition, whereas leaching of sulfonic acid groups is not significant. This effect is more pronounced in the largest-pore-size catalyst C3, which rapidly deactivates after one reaction cycle, whereas catalysts with a relatively medium and small average pore size (named, respectively, C2 and C1) deactivate after two reaction cycles and to a lesser extent. CHNS elemental analysis showed that C1 and C3 experience a similar amount of carbonaceous deposition, suggesting that the increased reusability of the small-pore-size catalyst can be attributed to the presence of SO3H groups mostly present on the external surface, as corroborated by results on pore clogging obtained by NMR relaxation measurements. The increased reusability of the C2 catalyst is attributed to a lower amount of humin being formed and, at the same time, reduced pore clogging, which helps to maintain accessible the internal pore space.

Carbon Vacancies Steer the Activity in Dual Ni Carbon Nitride Photocatalysis.

The manipulation of carbon nitride (CN) structures is one main avenue to enhance the activity of CN-based photocatalysts. Increasing the efficiency of photocatalytic heterogeneous materials is a critical step toward the realistic implementation of sustainable schemes for organic synthesis. However, limited knowledge of the structure/activity relationship in relation to subtle structural variations prevents a fully rational design of new photocatalytic materials, limiting practical applications. Here, the CN structure is engineered by means of a microwave treatment, and the structure of the material is shaped around its suitable functionality for Ni dual photocatalysis, with a resulting boosting of the reaction efficiency toward many CX (X = N, S, O) couplings. The combination of advanced characterization techniques and first-principle simulations reveals that this enhanced reactivity is due to the formation of carbon vacancies that evolve into triazole and imine N species able to suitably bind Ni complexes and harness highly efficient dual catalysis. The cost-effective microwave treatment proposed here appears as a versatile and sustainable approach to the design of CN-based photocatalysts for a wide range of industrially relevant organic synthetic reactions.

Identification and characterization of two novel and differentially expressed isoforms of human α2- and α1-globin genes.

In most references, the transcription initiation site for the α2- and α1-globin genes has been described to lie 37 bp upstream of the translation initiation codon, however, a review of data repositories such as GenBank and Ensembl showed a report of the α2-globin transcription initiation site occurring at position -66 relative to the initiation codon. To confirm the occurrence of these isoforms for both the α2- and α1-globin genes and to document their expression levels, we initiated our current investigation. Total RNA from the peripheral blood of 15 healthy volunteers was analyzed using both semi-quantitative-polymerase chain reaction (PCR) and real-time (ReTi-PCR) protocols developed in our laboratory, with primers designed to enable distinction between the α2- and α1-globin transcripts.We observed two distinct PCR products for each of the globin genes. Subsequent DNA sequencing of 11 individual PCR products revealed that the α2- and α1-globin transcripts are present in both a long and a short isoform, initiating at positions -66 and -37, respectively. The shorter (-37) isoform is expressed approximately 10,000-100,000 times more strongly than the longer isoform, demonstrating differential expression within the healthy population. This study, for the first time, confirms the presence of two isoforms for both the α2- and α1-globin genes with varying transcription levels in healthy individuals. The short isoform is expressed at significantly higher levels than the longer isoform for both α2 and α1 genes. Therefore, based on our observations, we propose that despite the contribution of the long isoforms to the total α-globin RNA pool, the short isoforms are the main physiological transcripts.

Primary Definitive Treatment versus Ureteric Stenting in the Management of Acute Ureteric Colic: A Cost-Effectiveness Analysis.

Objectives: To analyze the differences in cost-effectiveness between primary ureteroscopy and ureteric stenting in patients with ureteric calculi in the emergency setting. Patients and Methods: Patients requiring emergency intervention for a ureteric calculus at a tertiary centre were analysed between January and December 2019. The total secondary care cost included the cost of the procedure, inpatient hospital bed days, emergency department (A&E) reattendances, ancillary procedures and any secondary definitive procedure. Results: A total of 244 patients were included. Patients underwent ureteric stenting (62.3%) or primary treatment (37.7%), including primary ureteroscopy (URS) (34%) and shock wave lithotripsy (SWL) (3.6%). The total secondary care cost was more significant in the ureteric stenting group (GBP 4485.42 vs. GBP 3536.83; p = 0.65), though not statistically significant. While mean procedural costs for primary treatment were significantly higher (GBP 2605.27 vs. GBP 1729.00; p < 0.001), costs in addition to the procedure itself were significantly lower (GBP 931.57 vs. GBP 2742.35; p < 0.001) for primary treatment compared to ureteric stenting. Those undergoing ureteric stenting had a significantly higher A&E reattendance rate compared with primary treatment (25.7% vs. 10.9%, p = 0.02) and a significantly greater cost per patient related to revisits to A&E (GBP 61.05 vs. GBP 20.87; p < 0.001). Conclusion: Primary definitive treatment for patients with acute ureteric colic, although associated with higher procedural costs than ureteric stenting, infers a significant reduction in additional expenses, notably related to fewer A&E attendances. This is particularly relevant in the COVID-19 era, where it is crucial to avoid unnecessary attendances to A&E and reduce the backlog of delayed definitive procedures. Primary treatment should be considered concordance with clinical judgement and factors such as patient preference, equipment availability and operator experience.