Glyco-functionalized dinuclear rhenium(i) complexes for cell imaging

The design, synthesis and photophysical characterization of four new luminescent glycosylated luminophores based on dinuclear rhenium complexes, namely Glyco-Re, are described. The derivatives have the general formula [Re2(\u3bc-Cl)2(CO)6(\u3bc-pydz-R)] (R-pydz = functionalized 1,2-pyridazine), where a sugar residue (R) is covalently bound to the pyridazine ligand in the \u3b2 position. Different synthetic pathways have been investigated including the so-called neo-glycorandomization procedure, affording stereoselectively glyco-conjugates containing glucose and maltose in a \u3b2 anomeric configuration. A multivalent dinuclear rhenium glycodendron bearing three glucose units is also synthesized. All the Glyco-Re conjugates are comprehensively characterized and their photophysical properties and cellular internalization experiments on human cervical adenocarcinoma (HeLa) cells are reported. The results show that such Glyco-Re complexes display interesting bio-imaging properties, i.e. high cell permeability, organelle selectivity, low cytotoxicity and fast internalization. These findings make the presented Glyco-Re derivatives efficient phosphorescent probes suitable for cell imaging applicatio

Ozone damage and tolerance in leaves of two poplar genotypes.

The effects induced by an acute ozone exposure were investigated in two poplar hybrids differen- tially O3 susceptible in terms of leaf injuries: Populus deltoides x maximowiczii, Eridano clone and..

Prevalence of Vertebral Fractures in Osteoporotic HIP Fractured Patients: The Focus Study

Osteoporosis is a multifactorial systemic skeletal disease, characterized by low bone mass and microarchitectural modifications of bone tissue, with a consequent increase in fragility fractures. Vertebral fractures are the most prevalent osteoporotic fractures and osteoporotic hip fractures are the most serious complication of osteoporosis resulting in increased mortality and high socio-economic cost. The coexistence of these two pathological conditions in elderly patients has been previously described, leading to even worse functional outcomes than each one alone. To determine the prevalence of vertebral fractures in osteoporotic hip fractured women and to evaluate the relationship between prevalence of vertebral fractures and pre-existing factors such us autonomy in daily life activity, quality of walking, numbers of falls, cognitive aspects and comorbidities. 946 osteoporotic hip fractured women aged more than 60 years and with an X-ray evaluation of spine were consecutively enrolled in 25 Orthopaedic, Physical Medicine and geriatric centers in Italy. After spine X-ray morphometry patients were divided in two groups: previous vertebral fracture (F) and no previous fracture (NF). Moreover anamnestic, demographical and outcome related data (ADL, IADL, CIRS, SPMSQ, FAC and RANKIN scale) were collected. Prevalent vertebral fractures were present in 502 (54%) patients. 119 (13.7%) patients had at least one severe fracture. The F compared to NF group showed statistically significant worse scores regarding the pre hip fracture values of RANKIN, CIRS, SPMSQ, IADL and the overall number of falls (p<0.001). Moreover the F group showed statistically significant lower values of serif 25(OH)D than NF group (p<.0.001). Previous Vertebral fractures in hip fractured patients are a common issue and negatively influence several functional and cognitive outcome measures in these patients

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study

Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326). Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction. NCT03846180 ( https://clinicaltrials.gov )

HIF-1α is over-expressed in leukemic cells from TP53-disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia

In chronic lymphocytic leukemia (CLL), the hypoxia-inducible factor 1 (HIF-1) regulates the response of tumor cells to hypoxia and their protective interactions with the leukemic microenvironment. In this study, we demonstrate that CLL cells from TP53-disrupted (TP53dis) patients have constitutively higher expression levels of the α-subunit of HIF-1 (HIF-1α) and increased HIF-1 transcriptional activity compared to the wild-type counterpart. In the TP53dis subset, HIF-1α upregulation is due to reduced expression of the HIF-1α ubiquitin ligase von Hippel-Lindau protein (pVHL). Hypoxia and stromal cells further enhance HIF-1α accumulation, independently of TP53 status. Hypoxia acts through the downmodulation of pVHL and the activation of the PI3K/AKT and RAS/ERK1-2 pathways, whereas stromal cells induce an increased activity of the RAS/ERK1-2, RHOA/RHOA kinase and PI3K/AKT pathways, without affecting pVHL expression. Interestingly, we observed that higher levels of HIF-1A mRNA correlate with a lower susceptibility of leukemic cells to spontaneous apoptosis, and associate with the fludarabine resistance that mainly characterizes TP53dis tumor cells. The HIF-1α inhibitor BAY87-2243 exerts cytotoxic effects toward leukemic cells, regardless of the TP53 status, and has anti-tumor activity in Em-TCL1 mice. BAY87-2243 also overcomes the constitutive fludarabine resistance of TP53dis leukemic cells and elicits a strongly synergistic cytotoxic effect in combination with ibrutinib, thus providing preclinical evidence to stimulate further investigation into use as a potential new drug in CLL

Galaxy stellar mass functions of different morphological types in clusters, and their evolution between z=0.8 and z=0

We present the galaxy stellar mass function (MF) and its evolution in clusters from z~0.8 to the current epoch, based on the WIde-field Nearby Galaxy-cluster Survey (WINGS) (0.04<z<0.07), and the ESO Distant Cluster Survey (EDisCS) (0.4<z <0.8). We investigate the total MF and find it evolves noticeably with redshift. The shape at M*>10^11 M' does not evolve, but below M*~10^10.8 M' the MF at high redshift is flat, while in the Local Universe it flattens out at lower masses. The population of M* = 10^10.2 - 10^10.8 M' galaxies must have grown significantly between z=0.8 and z=0. We analyze the MF of different morphological types (ellipticals, S0s and late-types), and find that also each of them evolves with redshift. All types have proportionally more massive galaxies at high- than at low-z, and the strongest evolution occurs among S0 galaxies. Examining the morphology-mass relation (the way the proportion of galaxies of different morphological types changes with galaxy mass), we find it strongly depends on redshift. At both redshifts, ~40% of the stellar mass is in elliptical galaxies. Another ~43% of the mass is in S0 galaxies in local clusters, while it is in spirals in distant clusters. To explain the observed trends, we discuss the importance of those mechanisms that could shape the MF. We conclude that mass growth due to star formation plays a crucial role in driving the evolution. It has to be accompanied by infall of galaxies onto clusters, and the mass distribution of infalling galaxies might be different from that of cluster galaxies. However, comparing with high-z field samples, we do not find conclusive evidence for such an environmental mass segregation. Our results suggest that star formation and infall change directly the MF of late-type galaxies in clusters and, indirectly, that of early-type galaxies through subsequent morphological transformations.Comment: MNRAS in press, 24 pages, 19 figures and 8 table

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)μg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio