Twists to the spin structure of the Ln9-diabolo motif exemplified in two {Zn2Ln2}[Ln9]{Zn2} coordination clusters

Two pentadecanuclear Zn4Ln11 [with Ln = Gd(1) or Dy(2)] coordination clusters, best formulated as {Zn2Ln2}[Ln9]{Zn2}, are presented. The central {Ln9} diabolo core has a {Zn2Ln2} handle motif pulling at two outer Ln ions of the central core via two {ZnLn} units, which also invest the system with C2 point symmetry. The resulting cluster motif is supported on two Zn “feet”, corresponding to the {Zn2} unit in the formula. A thorough investigation of the magnetic properties in the light of the properties of previously reported {Ln9} diabolo compounds was undertaken. Up to now, the spin structure of such diabolo motifs usually proves ambiguous. Our magnetic studies show that the orientation of the central spin in the {Gd9} diabolo plays a decisive role. In stabilizing the core by attachment of the {Zn}2+ “feet” and using the C2 symmetry related {ZnGd}5+ handles to influence the spin direction of the central Gd of the {Gd9} diabolo we can understand why the “naked” {Gd9} diabolo shows ambiguous spin structure. This then allowed us to elucidate the single molecule magnetic (SMM) properties of the Dy based compound 2 through disentangling the magnetic properties of the isostructural Gd based compound 1

A new family of high nuclearity CoII/DyIII coordination clusters possessing robust and unseen topologies

Mixing Co(NO3)2·6H2O/Dy(NO3)3·6H2O/(E)-4-(2-hydroxy-3-methoxybenzylideneamino)-2,3-dimethyl-1-phenyl-1,2-dihydropyrazol-5-one (HL)/pivalic acid/Et3N in various solvents results in the synthesis of seven compounds formulated as [CoII2DyIII2(μ3-MeO)2(L)2(piv)4(NO3)2] (3), [CoIIDyIII3(μ3-MeO)2(μ2-MeO)2(L)2(piv)2(NO3)3]·2(CH3OH) (4·2CH3OH), 2[CoII4DyIII4(μ2-O)2(μ3-OH)4(L)4(piv)8][CoII2DyIII5(μ3-OH)6(L)2(piv)8(NO3)4] (5), [CoII4DyIII4(μ2-O)2(μ3-OH)4(L)4(piv)8]·2(CH3CN) (6·2CH3CN), [CoII2DyIII5(μ3-OH)6(L)2(piv)8(NO3)4]·4(CH3CN) (7·4CH3CN), [CoII2DyIII2(μ3-OH)2(L)2(piv)2(NO3)2(EtOH)2(H2O)2](NO3)2·(EtOH) (8·EtOH) and [CoII4DyIII4(μ2-O)2(μ3-OH)4(L)4(piv)8] (9) with robust and unseen topologies. These show that the temperature and reaction time influence the formation of the final product. Preliminary magnetic studies, performed for 6 and 7 in the temperature range 2-300 K, are indicative of Single Molecule Magnet (SMM) behaviour. Moreover, analysis of the catalytic properties of compound 3 as an efficient catalyst for the synthesis of trans-4,5-diaminocyclopent-2-enones from 2-furaldehyde and primary amines has been carried out

The role of iron in the pathogenesis of endometriosis: a systematic review

Abstract STUDY QUESTION What is the role of iron in the pathophysiology of endometriosis? SUMMARY ANSWER Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory microenvironment and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity and malignant transformation. WHAT IS KNOWN ALREADY Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage. The evidence base is large, but no comprehensive reviews exist to summarise our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field. STUDY DESIGN, SIZE, DURATION This systematic review with a thematic analysis retrieved studies from the PubMed, Embase, Web of Science and Cochrane Library databases and searches were conducted from inception through to August 2022. Human and animal studies published in the English language were included and identified using a combination of exploded MeSH terms (‘Iron’ and ‘Endometriosis’) and free-text search terms (‘Iron’, ‘Ferric’, ‘Ferrous’, ‘Endometriosis’, ‘Endometrioma’). PARTICIPANTS/MATERIALS, SETTING, METHODS This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning the role of iron or iron complexes in the pathophysiology of endometriosis were included. Studies which did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included study by using the Newcastle-Ottawa scoring system. MAIN RESULTS AND THE ROLE OF CHANCE There were 776 records identified and these were screened down to 53 studies which met the eligibility criteria, including 6 animal and 47 human studies, with 3,556 individual participants. Iron excess is demonstrated in various tissues and fluids, including ovarian endometriomas, ovarian follicles, ectopic endometriotic lesions and peritoneal fluid. Markers of oxidative stress are strongly associated with high iron levels, and aberrant expression of iron-transport proteins has been demonstrated. Abnormal resistance to ferroptosis is likely. Iron-mediated oxidative stress is responsible for a pro-inflammatory micro-environment and is linked to subfertility, symptom severity and, possibly, malignant transformation. LIMITATIONS, REASONS FOR CAUTION A minority of the included studies were of objectively low quality with a high-risk of bias and may lead to misleading conclusions. Additionally, multiple studies failed to appropriately characterise the included patients by known confounding variables such as menstrual cycle phase, which may introduce bias to the findings. WIDER IMPLICATIONS OF THE FINDINGS Current literature depicts a central role of aberrant iron mechanics and subsequent oxidative stress in endometriosis. It is likely that iron excess is at least partly responsible for the persistence and proliferation of ectopic endometriotic lesions. As such, iron mechanics represent an attractive target for novel therapeutics, including iron chelators or effectors of the iron-oxidative stress pathway. There are significant gaps in our current understanding, and this review highlights and recommends several topics for further research. These include the role of iron chelation, resistance to ferroptosis, the relationship between iron excess and localised hypoxia, systemic iron pathophysiology in endometriosis, and the role of oxidative stress in malignant transformation. STUDY FUNDING/COMPETING INTEREST(S) J.W and S.P are supported by clinical fellowships at Liverpool University Hospital NHS Foundation trust. No additional funding was requested or required for the completion of this work. C.J.H. is supported by a Wellbeing of Women project grant (RG2137). D.K.H. is supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). The authors have no conflicts of interest to declare. REGISTRATION NUMBER A protocol was prospectively registered with the PROSPERO database in August 2021 (CRD42021272818) </jats:sec

IFN-λ3, not IFN-λ4, likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis

The International Liver Disease Genetics Consortium (ILDGC).Genetic variation in the IFNL3–IFNL4 (interferon-λ3–interferon-λ4) region is associated with hepatic inflammation and fibrosis1,2,3,4. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3–IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4–Ser70) and those encoding fully active IFN-λ4–Pro70. The two proposed functional variants (rs368234815 and rs4803217)5,6 were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis.M.E., M.D., and J.G. are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney, and by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1053206) and NHMRC Project Grants (APP1107178 and APP1108422). G.D. is supported by an NHMRC Fellowship (1028432)

Molecular diagnosis of Burkitt\u27s lymphoma.

BACKGROUND: The distinction between Burkitt\u27s lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma. METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt\u27s lymphoma. Burkitt\u27s lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt\u27s lymphoma, suggesting they represent cases of Burkitt\u27s lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt\u27s lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. CONCLUSIONS: Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma

Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL

A portable magneto-optical trap with prospects for atom interferometry in civil engineering

The high precision and scalable technology offered by atom interferometry has the opportunity to profoundly affect gravity surveys, enabling the detection of features of either smaller size or greater depth. While such systems are already starting to enter into the commercial market, significant reductions are required in order to reach the size, weight and power of conventional devices. In this article, the potential for atom interferometry based gravimetry is assessed, suggesting that the key opportunity resides within the development of gravity gradiometry sensors to enable drastic improvements in measurement time. To push forward in realizing more compact systems, techniques have been pursued to realize a highly portable magneto-optical trap system, which represents the core package of an atom interferometry system. This can create clouds of 10 7 atoms within a system package of 20 l and 10 kg, consuming 80 W of power. This article is part of the themed issue ‘Quantum technology for the 21st century’.</jats:p