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Coupling electrochemical CO2 reduction (CO2R) with a renewable energy source to create high‐value fuels and chemicals is a promising strategy in moving toward a sustainable global energy economy. CO2R liquid products, such as formate, acetate, ethanol, and propanol, offer high volumetric energy density and are more easily stored and transported than their gaseous counterparts. However, a significant amount (~30%) of  liquid products from electrochemical CO2R in a flow cell reactor cross the ion exchange membrane, leading to the substantial loss of system‐level Faradaic efficiency. This severe crossover of the liquid product has—until now—received limited attention. Here, we review promising methods to suppress liquid product crossover, including the use of bipolar membranes, solid‐state electrolytes, and cation‐exchange membranes‐based acidic CO2R systems. We then outline the remaining challenges and future prospects for the production of concentrated liquid products from CO2. Here we review promising methods to suppress liquid product crossover in flow cell reactor including the use of bipolar membranes, solid‐state electrolytes, and cation‐exchange membranes based acidic CO2R systems. The elimination of liquid product crossover is thus a key step to advance the achievement of renewable liquid fuels from CO2

Coupling electrochemical CO 2 reduction (CO 2 R) with a renewable energy source to create high‐value fuels and chemicals is a promising strategy in moving toward a sustainable global energy economy. CO 2 R liquid products, such as formate, acetate, ethanol, and propanol, offer high volumetric energy density and are more easily stored and transported than their gaseous counterparts. However, a significant amount (~30%) of  liquid products from electrochemical CO 2 R in a flow cell reactor cross the ion exchange membrane, leading to the substantial loss of system‐level Faradaic efficiency. This severe crossover of the liquid product has—until now—received limited attention. Here, we review promising methods to suppress liquid product crossover, including the use of bipolar membranes, solid‐state electrolytes, and cation‐exchange membranes‐based acidic CO 2 R systems. We then outline the remaining challenges and future prospects for the production of concentrated liquid products from CO 2 .

Oxylipins are bioactive oxidation products derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs) in the linoleic acid and α-linolenic desaturation pathways. This study determined if carbohydrate intake during prolonged and intensive cycling countered post-exercise increases in n-6 and n-3 PUFA-derived oxylipins. The research design utilized a randomized, crossover, counterbalanced approach with cyclists (N = 20, overnight fasted state, 7:00 am start) who engaged in four 75-km time trials while ingesting two types of bananas (Cavendish, Mini-yellow), a 6% sugar beverage, and water only. Carbohydrate intake was set at 0.2 g/kg every 15 minutes, and blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. Oxylipins were measured with a targeted liquid chromatography-multiple reaction monitoring mass spectrometric method. Significant time effects and substantial fold-increases (immediately post-exercise/pre-exercise) were measured for plasma levels of arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 43 of 45 oxylipins. Significant interaction effects (4 trials x 8 time points) were found for plasma ARA (P<0.001) and DHA (P<0.001), but not EPA (P = 0.255), with higher post-exercise values found in the water trial compared to the carbohydrate trials. Significant interaction effects were also measured for 12 of 45 oxylipins. The data supported a strong exercise-induced increase in plasma levels of these oxylipins during the water trial, with carbohydrate ingestion (both bananas types and the sugar beverage) attenuating oxylipin increases, especially those (9 of 12) generated from the cytochrome P-450 (CYP) enzyme system. These trials differences were especially apparent within the first three hours of recovery from the 75-km cycling bout. Prolonged and intensive exercise evoked a transient but robust increase in plasma levels of oxylipins, with a significant attenuation effect linked to acute carbohydrate ingestion for 28% of these, especially those generated through the CYP enzyme system. ClinicalTrials.gov, U.S. National Institutes of Health, NCT02994628.

Coenzyme Q10 (CoQ10), a lipid involved in ATP synthesis, exhibits very limited oral absorption, and its endogenous production decreases with ageing and with the occurrence of oxidative stress. Our group previously showed that monoglycerides omega-3 (MAG-OM3) increase OM3 plasma concentrations. Since CoQ10 is liposoluble, we hypothesised that its 48 h pharmacokinetics is higher when provided with MAG-OM3 compared to CoQ10 alone (in powder form) or added to rice oil (a neutral triacylglycerol oil). A randomised triple-blind crossover study was performed with fifteen men and fifteen women consuming the three supplements providing 200 mg of CoQ10 in a random order. Blood samples were collected before (t = 0) and 1, 3, 5, 6, 7, 8, 10, 11, 24 and 48 h after the supplement intake. Plasma total CoQ10 concentrations were analysed on ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometer (UPLC-MS/MS). Participants were 26⋅1 ± 4⋅8 years old. When CoQ10 was provided with rice or MAG-OM3 oils, the 48 h area under the curve (AUC 0–48 h) was approximately two times higher compared to when provided without an oil. The delta max concentration (ΔCmax) of plasma CoQ10 was, respectively, 2 (MAG-OM3) and 2⋅5 (rice oil) times higher compared to CoQ10 alone. There was a significant sex by treatment interaction (P = 0⋅0250) for the AUC 0–6 h supporting that in postprandial, men and women do not respond the same way to the different supplement. Women had a higher CoQ10 concentration 48 h after the single-dose intake compared to men. We conclude that CoQ10 supplements must be provided with lipids, and their kinetics is different between men and women.

Rifaximin is an antibiotic, acting locally in the gastrointestinal tract, which may exist in different crystal as well as amorphous forms. The current marketed rifaximin formulation contains polymorph alpha, the systemic bioavailability of which is very limited. This study compared the pharmacokinetics of this formulation with those of the amorphous form. Amorphous rifaximin was specifically prepared for the study and formulated as the marketed product. Two doses (200 mg and 400 mg) of both formulations were given to two groups of 12 healthy volunteers of either sex according to a single-blind, randomized, two-treatment, single-dose, two-period, cross-over design. Plasma and urine samples were collected at preset times (for 24 hours or 48 hours, respectively) after dosing, and assayed for rifaximin concentrations by high-performance liquid chromatography-mass spectrometry. For both dose levels, peak plasma concentration, area under the concentration-time curve, and cumulative urinary excretion were significantly higher after administration of amorphous rifaximin than rifaximin-α. Ninety percent confidence intervals for peak plasma concentration, area under the concentration-time curve, and urinary excretion ratios were largely outside the upper limit of the accepted (0.80-1.25) range, indicating higher systemic bioavailability of the amorphous rifaximin. The few adverse events recorded were not serious and not related to the study medications. Rifaximin-α, a crystal polymorph, does differ from the amorphous form, the latter being systemically more bioavailable. In this regard, care must be taken when using - as a medicinal product - a formulation containing even small amounts of amorphous form, which may alter the peculiar pharmacologic properties of this poorly absorbed antibiotic.

The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects. This was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews. The geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (C ) and area under the curve from time zero to the last measurable sampling time (AUC ) were 1.0776 (0.9201-1.2622) and 0.9978 (0.9538-1.0439) for fimasartan, 1.0038 (0.9782-1.0301) and 1.0055 (0.9828-1.0288) for amlodipine, and 1.0006 (0.9290-1.0776) and 0.9986 (0.9532-1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups. The 90% CI of the C of fimasartan was within the widened acceptance limit, ln(0.6984)-ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile, to the co-administration of its three constituent drugs.

The aim of this study was to assess the effect of the angiotensin II receptor blocker Irbesartan on protein damage by glycation, oxidation and nitration in patients with type 2 diabetes and microalbuminuria. In a double-masked randomised crossover trial of 52 hypertensive type 2 diabetic patients, antihypertensive treatment was replaced with bendroflumethiazide. After 2-months wash-out, patients were treated randomly with Irbesartan 300, 600, and 900 mg o.d., each dose for 2 months in a three-way crossover study. Glycation, oxidation and nitration adduct residues in plasma protein and related urinary free adducts were determined by stable isotopic dilution analysis liquid chromatography–tandem mass spectrometry . Treatment with Irbesartan decreased urinary excretion of advanced glycation endproducts (AGEs)—methylglyoxal- and glyoxal-derived hydroimidazolones, MG-H1 and G-H1. Urinary AGEs were decreased by 30–32%. In plasma protein, treatment with Irbesartan increased content of glycation adducts N ε -fructosyl-lysine, AGEs N ε -carboxymethyl-lysine, N ε -carboxyethyl-lysine and pentosidine, and also increased content of oxidation markers N -formylkynurenine and dityrosine. This was attributed to decreased clearance of plasma protein modified by N ε -fructosyl-lysine and oxidative markers through the glomerular filter tightened by Irbesartan treatment. Treatment of patients with type 2 diabetes with Irbesartan decreased urinary excretion of MG-H1, G-H1 and 3-NT, which may result from decreased exposure to these AGEs. This is likely achieved by blocking angiotensin II signalling and related down-regulation of glyoxalase 1 and may contribute to health benefits of Irbesartan therapy.

We analyze the structure of the perturbation expansion of the general multichannel Kondo model with channel anisotropic exchange couplings and in the presence of an external magnetic field, generalizing to this case the Anderson-Yuval technique. For two channels, we are able to map the Kondo model onto a generalized resonant level model. Limiting cases in which the equivalent resonant level model is solvable are identified. The solution correctly captures the properties of the two channel Kondo model, and also allows an analytic description of the cross-over from the non Fermi liquid to the Fermi liquid behavior caused by the channel anisotropy.