Reduction-induced facile isomerisation of metallacarboranes:synthesis and crystallographic characterisation of 4-Cp-4,1,2-closo-CoC₂B₉H₁₁

One-electron reduction of 3-Cp-3,1,2-closo-CoC2B9H11 followed by heating to reflux in DME (b.p. 85 °C) induces isomerisation to 4-Cp-4,1,2-closo-CoC2B9H11.</p

Icosahedral metallacarborane/carborane species derived from 1,1′-bis(o-carborane)

We thank ORSAS (GS) and the EPSRC (DE and DMcK supported by project EP/E02971X/1, WYM supported by project EP/I031545/1) for funding.Examples of singly-metallated derivatives of 1,1[prime or minute]-bis(o-carborane) have been prepared and spectroscopically and structurally characterised. Metallation of [7-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-7,8-nido-C2B9H10]2- with a {Ru(p-cymene)}2+ fragment affords both the unisomerised species [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (2) and the isomerised [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-(p-cymene)-2,1,8-closo-RuC2B9H10] (3), and 2 is easily transformed into 3 with mild heating. Metallation with a preformed {CoCp}2+ fragment also affords a 3,1,2-MC2B9-1[prime or minute],2[prime or minute]-C2B10 product [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-Cp-3,1,2-closo-CoC2B9H10] (4), but if CoCl2/NaCp is used followed by oxidation the result is the 2,1,8-CoC2B9-1[prime or minute],2[prime or minute]-C2B10 species [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-Cp-2,1,8-closo-CoC2B9H10] (5). Compound 4 does not convert into 5 in refluxing toluene, but does do so if it is reduced and then reoxidised, perhaps highlighting the importance of the basicity of the metal fragment in the isomerisation of metallacarboranes. A computational study of 1,1[prime or minute]-bis(o-carborane) is in excellent agreement with a recently-determined precise crystallographic study and establishes that the {1[prime or minute],2[prime or minute]-closo-C2B10H11} fragment is electron-withdrawing compared to H.Publisher PDFPeer reviewe

Social Europe. No 2/87

BACKGROUND: DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. RESULTS: Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. CONCLUSION: Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0408-0) contains supplementary material, which is available to authorized users

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. Population-based retrospective cohort study. Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. Warfarin use within 14 days of IE diagnosis. Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage. [Abstract copyright: Copyright © 2023. Published by Elsevier Ltd.

Syntheses, structures and redox properties of tris(pyrazolyl)borate-capped ruthenium vinyl complexes.

Reaction of RuHCl(CO)(PPh3)3 with aryl alkynes HCCC6H4R-4 [1: R = N(C6H4Me-4)2 (a), OMe (b), Me (c), CO2Me (d), NO2 (e)] gives the five-coordinate vinyl complexes Ru(CHCHC6H4R-4)Cl(CO)(PPh3)2 (2a–e). Reaction of 2a with excess PMe3 gives crystallographically characterised Ru{CHCHC6H4N(C6H4Me-4)2-4}Cl(CO)(PMe3)3 (3a), whilst reaction of 2a–e with KTp affords Ru(CHCHC6H4R-4)(CO)(PPh3)Tp (4a–e) bearing the facially capping Tp− ligand. Electrochemical and spectroelectochemical properties of 4a–e are consistent with substantial redox activity associated with the vinyl ligand, and these properties have been satisfactorily modelled by DFT based calculations of electronic structure

The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese

<p>Abstract</p> <p>Background</p> <p>Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).</p> <p>Methods</p> <p>We tested the polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls.</p> <p>Results</p> <p><it>RANTES </it>-28 G allele was associated with SARS susceptibility in Hong Kong Chinese (<it>P </it>< 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with <it>RANTES </it>-28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (<it>P </it>< 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (<it>P </it>= 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of <it>RANTES </it>data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (<it>P </it>= 0.011).</p> <p>Conclusion</p> <p><it>RANTES </it>-28 G allele plays a role in the pathogenesis of SARS.</p

A Brief Mindfulness-Based Family Psychoeducation Intervention for Chinese Young Adults With First Episode Psychosis: A Study Protocol

Family psychoeducation (FPE) has been recommended as a major component in the treatment of psychosis. Many previous studies have implemented an intensive program design that often only emphasized improvements in patients’ illness outcomes but the benefits for caregivers were limited. There have been calls for a time-limited but cost-effective FPE program to mitigate the looming reality of the suffering of people with psychosis and their families. A Brief Mindfulness-Based Family Psychoeducation for psychosis program is developed to reduce caregivers’ burden and promote young adult’s recovery. A randomized controlled trial will be conducted to compare this intervention with an ordinary FPE intervention. Both arms will involve six sessions, with a total contact time of 12 h. 300 caregivers of young adults who have experienced first episode psychosis within last 3 years will be recruited. Program effectiveness will be assessed by comparing outcomes measuring the caregivers’ burden, mental health symptoms, positive well-being, and the young adult’s mental health symptoms during the study and at 9-month post-randomization. The role of expressed emotions, interpersonal mindfulness, and non-attachment in mediating these outcomes will be explored. An additional qualitative approach Photovoice is selected to explore the complex family experiences and the benefits of mindfulness from the caregivers’ personal perspectives.Trial Registration: The trial is registered with the United States Clinical Trials Registry (ClinicalTrials.gov): NCT03688009

The impact of compassion from others and self-compassion on psychological distress, flourishing, and meaning in life among university students

Objectives: Research shows that compassion from others and from the self may enable university students to face, overcome, and bounce back from adversity and generate a greater sense of thriving and meaning in life. However, the underlying processes are largely unknown. The present study aimed to examine the associations of compassion with psychological distress, flourishing, and meaning in life among university students and explore the mechanisms underlying these associations. Methods: A total of 536 Hong Kong university students completed questionnaires measuring their experiences of compassion from others, self-compassion, resilience, psychological distress, flourishing, and meaning in life. Results: Serial mediation analyses showed that compassion from others was associated positively with self-compassion, which was, in turn, linked to greater resilience and consequently lower levels of psychological distress and higher levels of flourishing and meaning in life. Conclusions: Our findings reveal the associations of compassion from others and self-compassion with the well-being and life meaning of university students. The findings highlight the importance of being open and receptive to love and kindness from others. The findings also point to the importance of developing a caring attitude toward oneself

Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells

Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis