Faraday Discussions最新文献

Myelodysplastic syndromes (MDS) are a family of myeloid cancers with diverse genotypes and phenotypes characterized by ineffective haematopoiesis and risk of transformation to acute myeloid leukaemia (AML). Some epidemiological data indicate that MDS incidence is increasing in resource-rich regions but this is controversial. Most MDS cases are caused by randomly acquired somatic mutations. In some patients, the phenotype and/or genotype of MDS overlaps with that of bone marrow failure disorders such as aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and AML. Prognostic systems, such as the revised International Prognostic Scoring System (IPSS-R), provide reasonably accurate predictions of survival at the population level. Therapeutic goals in individuals with lower-risk MDS include improving quality of life and minimizing erythrocyte and platelet transfusions. Therapeutic goals in people with higher-risk MDS include decreasing the risk of AML transformation and prolonging survival. Haematopoietic cell transplantation (HCT) can cure MDS, yet fewer than 10% of affected individuals receive this treatment. However, how, when and in which patients with HCT for MDS should be performed remains controversial, with some studies suggesting HCT is preferred in some individuals with higher-risk MDS. Advances in the understanding of MDS biology offer the prospect of new therapeutic approaches.

Copper clusters on carbide surfaces have shown a high catalytic activity towards methanol formation. To understand the interaction between CO₂ and the catalytically active sites during this process and the role that carbon atoms could play in this, they are modeled by copper clusters, with carbon atoms incorporated. The formed clusters Cu_nC_m^? (n = 3–10, m = 1–2) are reacted with CO₂ and investigated by IR multiple-photon dissociation (IR-MPD) spectroscopy to probe the degree of CO₂ activation. IR spectra for the reaction products [Cu_nC·CO₂]^?, (n = 6–10), and [Cu_nC₂·CO₂]^?, (n = 3–8) are compared to reference spectra recorded for products formed when reacting the same cluster sizes with CO, and with density functional theory (DFT) calculated spectra. The results reveal a size- and carbon load-dependent activation and dissociation of CO₂. The complexes [Cu_nC·CO₂]^? with n = 6 and 10 show predominantly molecular activation of CO₂, while those with n = 7–9 show only dissociative adsorption. The addition of the second carbon to the cluster leads to the exclusive molecular activation of the CO₂ on all measured cluster sizes, except for Cu₅C₂^? where CO₂ dissociates. Combining these findings with DFT calculations leads us to speculate that at lower carbon-to-metal ratios (CMRs), the C can act as an oxygen anchor facilitating the OCO bond rupture, whereas at higher CMRs the carbon atoms increasingly attract negative charge, reducing the Cu cluster’s ability to donate electron density to CO₂, and consequently its ability to activate CO₂.

Asplenia (the congenital or acquired absence of the spleen) and hyposplenism (defective spleen function) are common causes of morbidity and mortality. The spleen is a secondary lymphoid organ that is responsible for the regulation of immune responses and blood filtration. Hence, asplenia or hyposplenism increases susceptibility to severe and invasive infections, especially those sustained by encapsulated bacteria (namely, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b). Asplenia is predominantly due to splenectomy for either traumatic events or oncohaematological conditions. Hyposplenism can be caused by several conditions, including haematological, infectious, autoimmune and gastrointestinal disorders. Anatomical disruption of the spleen and depletion of immune cells, especially IgM memory B cells, seem to be predominantly responsible for the clinical manifestations. Early recognition of hyposplenism and proper management of asplenia are warranted to prevent overwhelming post-splenectomy infections through vaccination and antibiotic prophylaxis. Although recommendations are available, the implementation of vaccination strategies, including more effective and immunogenic vaccines, is needed. Additionally, screening programmes for early detection of hyposplenism in high-risk patients and improvement of patient education are warranted.

During the past 10 years, biological electron cryo-microscopy (cryoEM) has undergone a process of rapid transformation. Many things we could only dream about a decade ago have now become almost routine. Nevertheless, a number of challenges remain, to do with sample preparation, the correlation between tomographic analysis and light microscopy, data validation, and the growing impact of artificial intelligence and structure prediction. This year’s Faraday Discussion examined these challenges in some detail. The concluding remarks present a concise summary of the meeting and a brief outlook to the future.