Ruthenium (0) complexes with NHC tetrazolylidene ligands: Synthesis, characterization and reactivity

Here we present two new phenyl-tetrazolylidene carbenes as ligands in non-mesoionic (1,4-substitution pattern) and mesoionic (1,3-substitution pattern) tetrazolylidene-cyclopentadienone ruthenium(0) complexes namely 1 and 2 respectively. The complexes have been obtained in good yield and fully characterized; X-ray structure determination confirmed the binding mode of the ligand for 2. Reactivity studies has been performed in order to shed light on the fact that the phenyl substituent position in the heterocyclic ligand can seriously change complexes behavior and stabilit

Iridium-Functionalized Cellulose Microcrystals as a Novel Luminescent Biomaterial for Biocomposites

Microcrystalline cellulose (MCC) is an emerging material with outstanding properties in many scientific and industrial fields, in particular as an additive in composite materials. Its surface modification allows for the fine-tuning of its properties and the exploitation of these materials in a plethora of applications. In this paper, we present the covalent linkage of a luminescent Ir-complex onto the surface of MCC, representing the first incorporation of an organometallic luminescent probe in this biomaterial. This goal has been achieved with an easy and sustainable procedure, which employs a Bronsted-acid ionic liquid as a catalyst for the esterification reaction of -OH cellulose surface groups. The obtained luminescent cellulose microcrystals display high and stable emissions with the incorporation of only a small amount of iridium (III). Incorporation of MCC-Ir in dry and wet matrices, such as films and gels, has been also demonstrated, showing the maintenance of the luminescent properties even in possible final manufacturers

A synergic nanoantioxidant based on covalently modified halloysite-trolox nanotubes with intra-lumen loaded quercetin

We describe the preparation and properties of the first example of a synergic nanoantioxidant, obtained by different functionalizations of the external surface and the inner lumen of halloysite nanotubes (HNTs). Trolox, a mimic of natural α-tocopherol, was selectively grafted on the HNT external surface; while quercetin, a natural polyphenolic antioxidant, was loaded into the inner lumen to afford a bi-functional nanoantioxidant, HNT-Trolox/Que, which was investigated for its reactivity with transient peroxyl radicals and a persistent 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical in comparison with the corresponding mono-functional analogues HNT-Trolox and HNT/Que. Both HNT-Trolox and HNT/Que showed good antioxidant performance in the inhibited autoxidation of organic substrates; however HNT-Trolox/Que protection by reaction with peroxyl radicals was 35% higher in acetonitrile and 65% in chlorobenzene, as compared to the expected performance based on the sum of contributions of NHT-Trolox and NHT/Que. Similar enhancement was observed also in the trapping of DPPH• radicals. Synergism between the distinct antioxidant functions was based on the rapid reaction of externally exposed Trolox (rate constant with peroxyl radicals was 1.1 × 106 M-1 s-1 and 9 × 104 M-1 s-1 respectively in chlorobenzene and acetonitrile, at 30 °C), followed by its regeneration by quercetin released from the HNT lumen. The advantages of this novel nanoantioxidant are discussed

4-Phenyl-1,2,3-triazoles as Versatile Ligands for Cationic Cyclometalated Iridium(III) Complexes

Five cationic iridium(III) complexes (1-5) were synthesized exploiting two triazole-based cyclometalating ligands, namely, 1-methyl-4-phenyl-1H-1,2,3-triazole (A) and the corresponding mesoionic carbene 1,3-dimethyl-4-phenyl-1H-1,2,3-triazol-5-yliclene (B). From the combination of these two ligands and the ancillary one, i.e., 4,4'-di-tert-butyl-2,2'-bipyridine (for 1-3) or tert-butyl isocyanide (for 4 and 5), not only the typical bis-heteroleptic complexes but also the much less explored tris-heteroleptic analogues (2 and 5) could be synthesized. The redox and emission properties of all of the complexes are effectively fine-tuned by the different ligands: (i) cyclometalating ligand A induces a stronger highest occupied molecular orbital (HOMO) stabilization compared to B and leads to complexes with progressively narrower HOMO-lowest unoccupied molecular orbital (LUMO) and redox gaps, and lower emission energy; (ii) complexes 1-3, equipped with the bipyridine ancillary ligand, display fully reversible redox processes and emit from predominantly metal-to-ligand charge transfer (MLCT) states with high emission quantum yields, up to 60% in polymeric matrix; (iii) complexes 4 and 5, equipped with high-field isocyanide ligands, display irreversible redox processes and high-energy emission from strongly ligand-centered triplets with long emission lifetimes but relatively low quantum yields (below 6%, both in room-temperature solution and in solid state). This work demonstrates the versatility of phenyl-triazole derivatives as cyclometalating ligands with different chelation modes (i.e., C<^>N and C<^>C:) for the synthesis of photoactive iridium(III) complexes with highly tunable properties

Evaluating the impact of a maternal health voucher programme on service use before and after the introduction of free maternity services in Kenya: a quasi-experimental study.

INTRODUCTION: From 2006 to 2016, the Government of Kenya implemented a reproductive health voucher programme in select counties, providing poor women subsidised access to public and private sector care. In June 2013, the government introduced a policy calling for free maternity services to be provided in all public facilities. The concurrent implementation of these interventions presents an opportunity to provide new insights into how users adapt to a changing health financing and service provision landscape. METHODS: We used data from three cross-sectional surveys to assess changes over time in use of 4+ antenatal care visits, facility delivery, postnatal care and maternal healthcare across the continuum among a sample of predominantly poor women in six counties. We conducted a difference-in-differences analysis to estimate the impact of the voucher programme on these outcomes, and whether programme impact changed after free maternity services were introduced. RESULTS: Between the preintervention/roll-out phase and full implementation, the voucher programme was associated with a 5.5% greater absolute increase in use of facility delivery and substantial increases in use of the private sector for all services. After free maternity services were introduced, the voucher programme was associated with a 5.7% higher absolute increase in use of the recommended package of maternal health services; however, disparities in access to facility births between voucher and comparison counties declined. Increased use of private sector services by women in voucher counties accounts for their greater access to care across the continuum. CONCLUSIONS: Our findings show that the voucher programme is associated with a modest increase in women's use of the full continuum of maternal health services at the recommended timings after free maternity services were introduced. The greater use of private sector services in voucher counties also suggests that there is need to expand women's access to acceptable and affordable providers

Dissecting Immunotherapy Strategies for Small Cell Lung Cancer: Antibodies, Ionizing Radiation and CAR-T

Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard of care and shed light on the pivotal role of the immune system. Despite improved survival in a subset of patients, a lot of them still do not benefit from first-line chemo-immunotherapy, and several studies are investigating whether different combination strategies (with both systemic and local treatments, such as radiotherapy) may improve patient outcomes. Moreover, research of biomarkers that may be used to predict patients’ outcomes is ongoing. In addition to ICIs, immunotherapy offers other different strategies, including naked monoclonal antibodies targeting tumor associated antigens, conjugated antibody, bispecific antibodies and cellular therapies. In this review, we summarize the main evidence available about the use of immunotherapy in SCLC, the rationale behind combination strategies and the studies that are currently ongoing in this setting, in order to give the reader a clear and complete view of this rapidly expanding topic

Evaluating the impact of a maternal health voucher programme on service use before and after the introduction of free maternity services in Kenya: a quasi-experimental study

INTRODUCTION: From 2006 to 2016, the Government of Kenya implemented a reproductive health voucher programme in select counties, providing poor women subsidised access to public and private sector care. In June 2013, the government introduced a policy calling for free maternity services to be provided in all public facilities. The concurrent implementation of these interventions presents an opportunity to provide new insights into how users adapt to a changing health financing and service provision landscape. METHODS: We used data from three cross-sectional surveys to assess changes over time in use of 4+ antenatal care visits, facility delivery, postnatal care and maternal healthcare across the continuum among a sample of predominantly poor women in six counties. We conducted a difference-in-differences analysis to estimate the impact of the voucher programme on these outcomes, and whether programme impact changed after free maternity services were introduced. RESULTS: Between the preintervention/roll-out phase and full implementation, the voucher programme was associated with a 5.5% greater absolute increase in use of facility delivery and substantial increases in use of the private sector for all services. After free maternity services were introduced, the voucher programme was associated with a 5.7% higher absolute increase in use of the recommended package of maternal health services; however, disparities in access to facility births between voucher and comparison counties declined. Increased use of private sector services by women in voucher counties accounts for their greater access to care across the continuum. CONCLUSIONS: Our findings show that the voucher programme is associated with a modest increase in women’s use of the full continuum of maternal health services at the recommended timings after free maternity services were introduced. The greater use of private sector services in voucher counties also suggests that there is need to expand women’s access to acceptable and affordable providers

Benzo[a]pyrene disrupts LH/hCG-dependent mouse Leydig cell steroidogenesis through receptor/Gαs protein targeting

Steroidogenesis of gonadal cells is tightly regulated by gonadotropins. However, certain polycyclic aromatic hydrocarbons, including Benzo[a]pyrene (BaP), induce reproductive toxicity. Several existing studies have considered higher than environmentally relevant concentrations of BaP on male and female steroidogenesis following long-term exposure. Also, the impact of short-term exposure to BaP on gonadotropin-stimulated cells is understudied. Therefore, we evaluated the effect of 1 nM and 1 μM BaP on luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e. the mouse tumor Leydig cell line mLTC1, and the human primary granulosa lutein cells (hGLC) post 8- and 24-h exposure. Cell signalling studies were performed by homogeneous time-resolved fluorescence (HTRF) assay, bioluminescence energy transfer (BRET) and Western blotting, while immunostainings and immunoassays were used for intracellular protein expression and steroidogenesis analyses, respectively. BaP decreased cAMP production in gonadotropin-stimulated mLTC1 interfering with Gαs activation. Therefore, decrease in gonadotropin-mediated CREB phosphorylation in mLTC1 treated with 1 μM BaP was observed, while StAR protein levels in gonadotropin-stimulated mLTC1 cells were unaffected by BaP. Further, BaP decreased LH- and hCG-mediated progesterone production in mLTC1. Contrastingly, BaP failed to mediate any change in cAMP, genes and proteins of steroidogenic machinery and steroidogenesis of gonadotropin-treated hGLC. Our results indicate that short-term exposure to BaP significantly impairs steroidogenic signalling in mLTC1 interfering with Gαs. These findings could have a significant impact on our understanding of the mechanism of reproductive toxicity by endocrine disruptors

The protein "mycoarray": a novel serological assay for the laboratory diagnosis of primitive endemic mycoses

A protein microarray containing fungal antigens (the "mycoarray") has been set up to provide rapid and appropriate serodiagnosis of primitive endemic mycoses, an important cause of morbidity and mortality in an increasingly high number of patients. The mycoarray consists of three antigen extracts (histoplasmin, coccidioidin and Coccidioides "TP") and antibody dilution curves were spotted on microarray slides. The arrays were processed with coccidioidomycosis and histoplasmosis patients\ufffd sera or with control sera and the occurring immunocomplexes were detected by indirect immunofluorescence. In agreement with clinical and microbiological diagnosis, the results distinguished between histoplasmosis and coccidioidomycosis patients. In addition, the assay could clearly discriminate between IgM and IgG antibody reactivity. No reactivity was ever observed in the arrays processed with negative control sera. Therefore, this pilot study demonstrates that the "mycoarray" is sensitive and specific enough to discriminate between healthy individuals and patients with histoplasmosis or coccidioidomycosis. Because of miniaturization and multiparametricity, the new assay cuts costs and processing time. Thus, once clinically validated and implemented as a large-scale array, the "mycoarray" will be ready to be applied to the daily clinical practice