Metal coordination determines the catalytic activity of IrO2 nanoparticles for the oxygen evolution reaction

Acord transformatiu CRUE-CSICH2 production through water electrolysis is a promising strategy for storing sunlight energy. For the oxygen evolution reaction, iridium oxide containing materials are state-of-the-art due to their stability in acidic conditions. Moreover, precious metal content can be reduced by using small nanoparticles that show high catalytic activities. We performed DFT calculations on a 1.2 nm large IrO2 Wulff-like stoichiometric nanoparticle model (IrO2) with the aim of determining the factors controlling the catalytic activity of IrO2 nanoparticles. Results show that at reaction conditions tetra- and tricoordinated iridium centers are not fully oxidized, the major species being IrO(OH) and IrO(OH)2, respectively. Although the computed overpotential show that all centers present relatively similar reactivities, low coordinated iridium centers tend to be more active than the pentacoordinates sites of the well-defined facets. These low coordination sites are likely more abundant on amorphous nanoparticles, which could be one of the factors explaining the higher catalytic activity observed for non-crystalline materials

3-Ethoxy-5,6,7,8-tetrahydro-1-hydroxyisoquinoline-4-carbonitrile, C12H14N2O2

Mr=218.25, monoclinic, P2l/n, a= 1.33 g cm-3, (Mo Ka) = 0.71069 A, µ=0.86 cm-1, 20.000(2), b = 6.219(1), c=8.794(1)A, β= F(000)= 464, T=298 K. Final R = 0.056 for 136994.31 (2)º, V = 1090.7(4)A3, Z=4 Dx= observed reflections. The pyridine ring is planar, two (carbonyl and carbonitrile) substituents deviate at the same side of the plane, while the remaining substituents deviate at the other side. The six-carbon-membered ring has a skew-boat form. Bond angles and lengths are similar to those observed in the literature. Enantiomeric molecules are hydrogen-bonded by means of the carbonyl O and the N atom of the isoquinoline moiety

Importance of the oxyl character on the IrO2 surface dependent catalytic activity for the oxygen evolution reaction

Acord transformatiu CRUE-CSICThe oxygen evolution reaction catalyst optimization is hindered because in the desirable acidic conditions the sole active catalysts are RuO and IrO. Thus, the understanding of the factors controlling the reactivity of these materials is mandatory. In this contribution, DFT (PBE-D2) periodic calculations are performed to analyze the catalytic activities of the main ((1 1 0), (0 1 1), (1 0 0) and (0 0 1)) IrO surfaces. Results show that the reaction only occurs if the Ir=O species on the surfaces exhibit an oxyl character. The water nucleophilic attack mechanism is the most favorable pathway on the (1 1 0), (1 0 0) and (0 0 1) surfaces. In contrast, for the (0 1 1) facet the oxo-coupling is preferred. The required overpotentials for the four IrO surfaces depend on the feasibility to oxidize the Ir-OH to Ir-O species and this is tuned by the coordination of the unsaturated iridium sites: the (1 0 0) and (0 0 1) surfaces appear to be more active than the (1 1 0) and (0 1 1)

Bis[1,3-bis(2-hydroxyphenyl)-1,3-propanedionato]bis(ethanol)zinc(II), C34H34O10Zn

Mr=668.0, triclinic, P1, a=13.028 (2), b=11.872(2), c=10.971(2) A, a=102.28 (1), β = 87.14(1), a=112.53(2)º, V = 1530.6(7)A3, Z = 2, Dx = 1.45 Mg m-3, (Mo Ka)=0.71069 A, µ= 0.889 mm-1, F(000)=696, T=295 K. Final R = 0.06 for 3025 observed reflections. The structure consists of chains of molecules parallel to [011] linked by hydrogen bonds. The Zn2+ ion is surrounded by six O atoms in a distorted octahedral shape. The 1,3-bis(2-hydroxyphenyl)-1,3, propanedionato anions act as bidentate ligands. The six-membered Zn-propanedione rings have half-chair form

The structure of dichlorobis[μ-(3-dimethylamino-1-propanethiolato)-μ-S,N]-dipalladium(II), (I) [Pd2(C5H12NS)2Cl2], and ac,bd,eg, fh-tetrakis[μ-(3-piperidinemethanethiolato)-μ-S,N]-tripalladium(II) dichloride dihydrate, (II) [Pd3(C6H12NS)4]Cl2.2H2O

Mr=520.15, monoclinic, P21/n, a=7.207(2), B=20.616(4), c=5.854(1) A, β=96.05(1)º, V=864.9(6)A3, Z=2, Dx=2.00 Mg m-3, Mo Ka, = 0.71069 A, µ=2.553 mm-1, F(000)=512, 298 K, R=0.060 for 1492 reflections. (II): Mr=947.07, triclinic, Pl, a=12.666(7), b=10.595(6), c=6.572(5)A, a=98.30(2), = 97.04(2), = 99.84(2)º, V=850(2)A3, Z=1, Dx=1.85 Mg m-3, Mo Ka, =0.71069 A, µ=1.958 mm-1, F(000)=490, 298 K, R=0.071 for 1879 reflections. (I) was solved by direct methods, using MULTAN and DIRDIF, (II) by the heavy-atom method. The four-membered Pd, S, Pd, S rings have a syn-exo conformation, with dihedral angles between the S, Pd, S planes of 154.4(2) and 133.0(3)º for (I) and (II), respectively

Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome

Preventive treatment can reverse cognitive impairment in chronic migraine

Objective: To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyse the degree of reversibility of any observed alterations following the use of preventive treatment. Background: CM is a highly disabling disease, and migraineurs often have associated comorbidities, such as subjective memory problems, that are involved in the development of cognitive impairment. Our hypotheses are that patients suffering from chronic migraine experience objective cognitive alterations that are not only due to the pain that they suffer or their current emotional state. Furthermore, preventive treatment should be capable of reversing, or at least reducing, the impact of CM on the cognition and QoL of migraineurs. Methods: The cognition and QoL of 50 control subjects and 46 patients with CM were assessed using a battery of tests, prior to the use of preventive treatment based on botulinum toxin or oral drugs and after 3 months of this treatment. Results: Compared with controls, patients with CM had lower scores on the assessment of cognitive performance (Rey-Osterrieth Complex Figure test [ROCF] (p<0.05), Trail Making Test [TMT] B) (p < 0.05) and QoL (p < 0.05). Three months after the use of preventive treatment, improvement was observed in all cognitive parameters (p < 0.05) and QoL (p < 0.05), except the ROCF copy task (p = 0.79). No statistically significant differences were observed when these outcomes were compared based on treatment. Conclusions: This study confirms poor cognitive performance that is not explained by migraine pain itself, as it occurs in the interictal period, irrespective of the patient's emotional status. Our findings show that these effects are reversible in some cases with preventive treatment of CM, reaffirming the important impact of this condition on the QoL of these patients, and the need to establish preventive treatment guidelines

Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor.

Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates. Knowledge on the effect that Prn deficiency has on infection and immunity to B. pertussis is crucial for the development of new strategies to control this disease. Here, we characterized the effect of Prn production by B. pertussis on human and murine dendritic cell (DC) maturation as well as in a murine model for pertussis infection. We incubated human monocyte-derived DCs (moDCs) with multiple isogenic Prn knockout (Prn-KO) and corresponding parental B. pertussis strains constructed either in laboratory reference strains with a Tohama I background or in a recently circulating clinical isolate. Results indicate that, compared to the parental strains, Prn-KO strains induced an increased production of pro-inflammatory cytokines by moDCs. This pro-inflammatory phenotype was also observed upon stimulation of murine bone marrow-derived DCs. Moreover, RNA sequencing analysis of lungs from mice infected with B. pertussis Prn-KO revealed increased expression of genes involved in cell death. These in vitro and in vivo findings indicate that B. pertussis strains which do not produce Prn induce a stronger pro-inflammatory response and increased cell death upon infection, suggesting immunomodulatory properties for Prn

Vitamin D Endocrine System and COVID-19. Treatment with Calcifediol

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity

Spain; ANCA; VasculitidesEspanya; ANCA; VasculitisEspaña; ANCA; VasculitisThe aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ± 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ± 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose