This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing ...different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2-4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4-6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (
< 0.0001) and a significant increase from T1 to T2 (
< 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (
< 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (
= 0.013) and T1 (
< 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.
Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general ...population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB status and different risk to develop active-TB disease. We enrolled TBI subjects as example of Mtb-containment, the active-TB as example of a replicating Mtb status, and the TBI-IMID as fragile population. To study the Mtb-specific response in a condition of possible Mtb sterilization, we longitudinally enrolled TBI subjects and active-TB patients before and after TB therapy. Peripheral blood mononuclear cells were stimulated overnight with Mtb peptides contained in TB1- and TB2-tubes of the Quantiferon-Plus kit. Then, we characterized by cytometry the Mtb-specific CD4 and CD8 T cells. In TBI-IMID, the TB therapy did not affect the ability of CD4 T cells to produce interferon-γ, tumor necrosis factor-α, and interleukin-2, their functional status, and their phenotype. The TB therapy determined a contraction of the triple functional CD4 T cells of the TBI subjects and active-TB patients. The CD45RA
CD27
T cells stood out as a main subset of the Mtb-specific response in all groups. Before the TB-preventive therapy, the TBI subjects had higher proportion of Mtb-specific CD45RA
CD27
CD4
T cells and the active-TB subjects had higher proportion of Mtb-specific CD45RA
CD27
CD4
T cells compared to other groups. The TBI-IMID patients showed a phenotype similar to TBI, suggesting that the type of IMID and the IMID therapy did not affect the activation status of Mtb-specific CD4 T cells. Future studies on a larger and better-stratified TBI-IMID population will help to understand the change of the Mtb-specific immune response over time and to identify possible immune biomarkers of Mtb-containment or active replication.
Objective
Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, ...through the
ex-vivo
assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform.
Methods
Two cohorts were evaluated: in “study population A”, plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized “COVID-19 patients” and 29 “NO COVID-19 controls” all unvaccinated. In “study population B”, 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis.
Results
Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in “study population A”. Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in “study population B”. Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8
+
and NK cells.
Conclusion
This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further
in vivo
investigations.
We demonstrate that the addition of 1-butyl-1-methylpyrrolidinium hexafluorophosphate (Py14PF6) to 1.0 M LiPF6 in ethylene carbonate-dimethyl carbonate (LP30) widens the temperature range, in which ...the electrolyte mixtures are ion conductive and safe. Specifically, at the concentrations of Py14PF6 above 50 wt%, the electrolyte mixtures exhibit a flash point higher than room temperature and fulfill the requirements of liquids having controlled flammability. In this concentration range, also crystallization of the mixtures is completely suppressed, and low temperature ionic conductivity is improved. With respect to the electrochemical properties at room temperature, electrochemical stability window is widened by the addition of Py14PF6 to LP30. However, it comes at the cost of slightly increased overall impedance and overpotential in Li | Li symmetric cells. We utilize these mixed electrolytes in high voltage Li | LiNi0.5Mn1.5O4 cells. In the presence of 30 wt% and 50 wt% of Py14PF6 in LP30, the cells exhibit high specific capacity of about 110 mAh g−1 over 200 cycles and improved coulombic efficiency, suggesting Py14PF6 is a promising additive for the electrolyte in high-voltage, stable and safe lithium batteries.
There is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to ...identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures.
The discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20). Their sera were analyzed for 40 cytokines/chemokines and activity of adenosine deaminase (ADA) isozymes. A prediction model was designed to differentiate ATB from untreated LTBI using sparse partial least squares (sPLS) and logistic regression analyses. Serum samples of two independent cohorts (national and international) were used for validation.
sPLS regression analyses identified C-C motif chemokine ligand 1 (CCL1), C-reactive protein (CRP), C-X-C motif chemokine ligand 10 (CXCL10), and vascular endothelial growth factor (VEGF) as the most discriminating biomarkers. These markers and ADA(2) activity were significantly increased in ATB compared to untreated LTBI (p ≤ 0.007). Combining CCL1, CXCL10, VEGF, and ADA2 activity yielded a sensitivity and specificity of 95% and 90%, respectively, in differentiating ATB from untreated LTBI. These findings were confirmed in the validation cohort including remotely acquired untreated LTBI participants.
The biomarker signature of CCL1, CXCL10, VEGF, and ADA2 activity provides a promising tool for differentiating patients with ATB from non-treated LTBI individuals.
In this work, the use of
-methyl-
-propylpiperidinium difluoro(oxalato)borate Pip
DFOB ionic liquid (IL), originally synthesized in our laboratory, as an additive for liquid electrolytes in ...lithium-ion batteries (LIBs), is proposed. The synthesized IL exhibits glass and melting transitions at -70.9 °C and 17.1 °C, respectively, and a thermal decomposition temperature over 230 °C. A mixture based on 1.0 M LiPF
in 1:1
/
ethylene carbonate (EC): dimethyl carbonate (DMC) electrolyte solution (so called LP30) and the IL was prepared and tested in lithium metal cells versus two different commercially available carbonaceous electrodes, i.e., graphite (KS6) and graphene (GnP), and versus a high voltage LiNi
Mn
O
(LNMO) cathode. A noticeable improvement was observed for Li|LNMO cells with an IL-added electrolyte, which exhibited a high specific capacity above 120 mAh g
with a Coulombic efficiency above 93% throughout 200 cycles, while the efficiency fell below 80% after 80 cycles with the absence of IL. The results confirm that the IL is promising additive for the electrolyte, especially for a longer cycle life of high-voltage cells.
The oxygen reduction reaction (ORR) is an important challenge in the development and large-scale distribution of energy conversion devices, especially low-temperature proton exchange membrane (PEM) ...fuel cells. In order to speed up the ORR kinetics and improve fuel cell performance, iron-doped calcium titanate (CTFO) is proposed as a cocatalyst. Fundamental physical and chemical characterizations by means of X-ray diffraction, infrared spectroscopy, and morphological and thermal analyses for the understanding of the functional features of the proposed materials were carried out. Composite catalysts containing different amounts of CTFO additive with respect to platinum (i.e., Pt:CTFO 1:0.5 and 1:1 wt:wt) were studied using a rotating disk electrode (RDE). Fuel cell tests were performed at 80 °C under 30% and 80% relative humidity. The best Pt:CTFO composite catalyst was compared to a bare Pt/C and a Pt/C:CaTiO3−δ 1:1 catalyst, revealing superior performances of the latter at high relative humidity fuel cell operation, as a combined result of an optimized electrolyte-electrode interface and improved ORR kinetics due to the inorganic additive.
We report a new class of quaternary polymer electrolyte membranes that comprise poly(ethylene oxide) (PEO), lithium trifluoromethanesulfonylimide (LiTFSI), N‐alkyl‐N‐butylpyrrolidinium ...bis(trifluoromethanesulfonyl)imide (PyrA,4TFSI) as an ionic liquid, and a SiO2 filler. The results of differential scanning calorimetry indicate that the addition of SiO2 and different ionic liquids induces a decrease in the PEO melting enthalpy, which thereby increases the ionic conductivity and the Li transference number. The electrochemical stability is proved by using impedance spectroscopy and cyclic voltammetry. Galvanostatic cycling of Li/LiFePO4 cells, which comprise the quaternary polymer electrolytes, revealed their superior performance compared to conventional PEO‐Li salt electrolytes. In the course of this investigation, a synergistic effect of the combined ionic liquid‐ceramic filler modification could be proved at temperatures close to 50 °C.
Electrolyte right! A new and attractive electrolyte based on polyethylene oxide and N‐butyl‐N‐ethyl‐pyrrolidinium bis(trifluoromethanesulfonyl)imide ionic liquid as plasticizer shows high conductivity at medium to low temperatures. This allows its employment in a solid polymer lithium battery using LiFePO4 as the cathode and its efficient operation at temperatures of about 50 °C.
Here, two ionic liquids, N‐ethoxyethyl‐N‐methylmorpholinium bis(trifluoromethanesulfonyl)imide (M1,2O2TFSI) and N‐ethoxyethyl‐N‐methylpiperidinium bis(trifluoromethanesulfonyl)imide (P1,2O2TFSI) were ...synthesized and compared. Fundamental relevant properties, such as thermal and electrochemical stability, density, and ionic conductivity were analyzed to evaluate the effects caused by the presence of the ether bond in the side chain and/or in the organic cation ring. Upon lithium salt addition, two electrolytes suitable for lithium batteries applications were found. Higher conducting properties of the piperidinium‐based electrolyte resulted in enhanced cycling performances when tested with LiFePO4 (LFP) cathode in lithium cells. When mixing the P1,2O2TFSI/LiTFSI electrolyte with a tailored alkyl carbonate mixture, the cycling performance of both Li and Li–ion cells greatly improved, with prolonged cyclability delivering very stable capacity values, as high as the theoretical one in the case of Li/LFP cell configurations.
A safer electrolyte: A lithium–ion battery, delivering very stable prolonged capacity with 100 % Coulombic efficiency, is proposed by coupling a new ionic liquid‐based electrolyte with Sn/C anode and LiFePO4 cathode.
Tetrapyrazinoporphyrazine (TPysPz) ligands and metal complexes find, generally, application as electronic materials and catalysts. Considering the limited application of Titanium (Ti), we prepared ...and characterized a family of ligands and Ti‐based complexes of tetrakis‐2,3‐5,6‐di‐R8‐pyrazinoporphyrazine (R = H, 2‐Py, Ph). UV/Vis measurements in different solvents confirm molecular aggregation, which results more pronounced in the presence of 2‐pyridil and phenyl substituents on the macrocycle edge. Because of low solubility, solid state NMR was applied for structure characterization. Additional IR and MALDI‐TOF were carried out to complete the characterization. Cyclic voltammetry in DMSO/Bu4NBF4 0.1 m unveiled that our Ti complexes can take part in up to five redox events. The first two quasi‐reversible reductions involve Ti(IV), whereas the further to or three occur at the expense of the TPysPz macrocycle. To test the applicability of our compounds as catalytic materials, we performed a preliminary cyclic voltammetry investigation in the solid‐state, which showed typical peaks of hydrogen redox reactions.
Tetrapyrazinoporphyrazines are privileged frameworks present in ligands and metal complexes. Choosing titanium as metal center, herein, we unveil the synthesis, the characterization and the electrochemical behavior of tetrakis‐2,3‐5,6‐di‐R8‐pyrazinoporphyrazine (R = H, 2‐Py, Ph) ligands and Ti complexes.
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