Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Glutathione-Dependent Pathways in Cancer Cells.

The most abundant tripeptide-glutathione (GSH)-and the major GSH-related enzymes-glutathione peroxidases (GPxs) and glutathione S-transferases (GSTs)-are highly significant in the regulation of tumor cell viability, initiation of tumor development, its progression, and drug resistance. The high level of GSH synthesis in different cancer types depends not only on the increasing expression of the key enzymes of the γ-glutamyl cycle but also on the changes in transport velocity of its precursor amino acids. The ability of GPxs to reduce hydroperoxides is used for cellular viability, and each member of the GPx family has a different mechanism of action and site for maintaining redox balance. GSTs not only catalyze the conjugation of GSH to electrophilic substances and the reduction of organic hydroperoxides but also take part in the regulation of cellular signaling pathways. By catalyzing the S-glutathionylation of key target proteins, GSTs are involved in the regulation of major cellular processes, including metabolism (e.g., glycolysis and the PPP), signal transduction, transcription regulation, and the development of resistance to anticancer drugs. In this review, recent findings in GSH synthesis, the roles and functions of GPxs, and GST isoforms in cancer development are discussed, along with the search for GST and GPx inhibitors for cancer treatment.

Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. METHODS: The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy ≥65-year-olds in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein-based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% CI >0.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. RESULTS: Of 1403 participants randomized, 1399 received vaccinations (median [range] age, 70 [65‒91] years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin. CONCLUSION: The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older adult population. CLINICAL TRIAL REGISTRATION: NCT05301322.

S-Glutathionylation and S-Nitrosylation as Modulators of Redox-Dependent Processes in Cancer Cell.

Development of oxidative/nitrosative stress associated with the activation of oncogenic pathways results from the increase in the generation of reactive oxygen and nitrogen species (ROS/RNS) in tumor cells, where they can have a dual effect. At high concentrations, ROS/RNS cause cell death and limit tumor growth at certain phases of its development, while their low amounts promote oxidative/nitrosative modifications of key redox-dependent residues in regulatory proteins. The reversibility of such modifications as S-glutathionylation and S-nitrosylation that proceed through the electrophilic attack of ROS/RNS on nucleophilic Cys residues ensures the redox-dependent switch in the activity of signaling proteins, as well as the ability of these compounds to control cell proliferation and programmed cell death. The content of S-glutathionylated and S-nitrosylated proteins is controlled by the balance between S-glutathionylation/deglutathionylation and S-nitrosylation/denitrosylation, respectively, and depends on the cellular redox status. The extent of S-glutathionylation and S-nitrosylation of protein targets and their ratio largely determine the status and direction of signaling pathways in cancer cells. The review discusses the features of S-glutathionylation and S-nitrosylation reactions and systems that control them in cancer cells, as well as their relationship with redox-dependent processes and tumor growth.

Potentiation of Cisplatin Cytotoxicity in Resistant Ovarian Cancer SKOV3/Cisplatin Cells by Quercetin Pre-Treatment.

Previously, we demonstrated that the overexpression of antioxidant enzymes (SOD-1, SOD-2, Gpx-1, CAT, and HO-1), transcription factor NFE2L2, and the signaling pathway (PI3K/Akt/mTOR) contribute to the cisplatin resistance of SKOV-3/CDDP ovarian cells, and treatment with quercetin (QU) alone has been shown to inhibit the expression of these genes. The aim of this study was to expand the previous data by examining the efficiency of reversing cisplatin resistance and investigating the underlying mechanism of pre-treatment with QU followed by cisplatin in the same ovarian cancer cells. The pre-incubation of SKOV-3/CDDP cells with quercetin at an optimum dose prior to treatment with cisplatin exhibited a significant cytotoxic effect. Furthermore, a long incubation with only QU for 48 h caused cell cycle arrest at the G1/S phase, while a QU pre-treatment induced sub-G1 phase cell accumulation (apoptosis) in a time-dependent manner. An in-depth study of the mechanism of the actions revealed that QU pre-treatment acted as a pro-oxidant that induced ROS production by inhibiting the thioredoxin antioxidant system Trx/TrxR. Moreover, QU pre-treatment showed activation of the mitochondrial apoptotic pathway (cleaved caspases 9, 7, and 3 and cleaved PARP) through downregulation of the signaling pathway (mTOR/STAT3) in SKOV-3/CDDP cells. This study provides further new data for the mechanism by which the QU pre-treatment re-sensitizes SKOV-3/CDDP cells to cisplatin.

Oxidative Stress and Redox-Dependent Signaling in Prostate Cancer.

Tumor emergence and progression is complicated by the dual role of reactive oxygen species (ROS). Low concentrations of ROS are essential for many intracellular metabolic processes and cell proliferation, while excessive ROS generation disrupts the mechanisms of cancer suppression, leading to the cell damage and death. A long-term imbalance in the ROS/antioxidant ratio and upregulation of the ROS generation due to the reduced efficacy of the antioxidant defense system cause chronic oxidative stress resulting in the damage of proteins, lipid, and DNA molecules and cancer development. Numerous data demonstrate that prostate cancer (the most common cancer in males) is associated with the development of oxidative stress. However, the reasons for the emergence of prostate cancer, as well as changes in the redox signaling and cellular redox homeostasis in this disease, are still poorly understood. The review examines the role of prooxidant and antioxidant enzyme systems, the imbalance in their activity leading to the oxidative stress development, changes in the key components of redox signaling, and the role of microRNAs in the modulation of redox status of cancer cells in prostate cancer.

Does the uterine microbiota affect the reproductive outcomes in women with recurrent implantation failures?

BACKGROUND: Inefficiency of in vitro fertilization (IVF) programs can be caused by implantation failures. The uterine microbiota can influence the implantation process. However, it still remains unclear whether opportunistic microorganisms detected in the endometrium have a negative impact on the implantation success. The aim of our study was to evaluate the influence of the uterine microbiota on the embryo implantation success in patients undergoing assisted reproductive technologies. METHODS: The study included 130 women diagnosed with infertility. The patients were divided into three groups: group I included women with the first IVF attempt (n = 39); group II included patients with recurrent implantation failure following embryo transfer with ovarian stimulation (n = 27); group III consisted of women with recurrent implantation failure following frozen-thawed embryo transfer (n = 64). We performed microbiological examination of the embryo transfer catheter which was removed from the uterine cavity after embryo transfer; cervical discharge of all the patients was studied as well. Thirty patients were selected for metagenomic sequencing. RESULTS: The study showed that the uterine cavity is not free of microorganisms. A total of 44 species of microorganisms were detected: 26 species of opportunistic organisms and 18 species of commensals (14 species of lactobacilli and 4 species of bifidobacteria). Obligate anaerobic microorganisms and Gardnerella vaginalis were detected more frequently in group I compared to group III (strict anaerobes-15.4 and 1.6%; G. vaginalis-12.8 and 1.6%, respectively) (p < 0.05). However, this fact did not have a negative influence on the pregnancy rate: it was 51.3% in group I, it was 29.6% and 35.9% in women with recurrent implantation failures, respectively. CONCLUSION: Opportunistic microorganisms which were revealed in low or moderate titers (103-105 CFU/ml) in the uterine cavity and cervical canal did not affect the pregnancy rate in the women in the study groups. The microflora of the uterine cavity and cervical canal differed in qualitative composition in 87.9% of patients, therefore, we can suggest that the uterine cavity may form its own microbiota. The microbiota of the uterine cavity is characterized by fewer species diversity compared to the microbiota of the cervical canal.

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin.

Polyphenols are considered popular ingredients in the pharmaceutical and medical fields due to their preventive and therapeutic properties. However, the potential effects and mechanisms of action of individual polyphenols remain largely unknown. Herein, we analyzed recent data on the synthetic pathways, features, and similarity of the properties of quercetin, as the most famous flavonoid, and curcumin, a representative of curcuminoids that despite their anti-oxidant activity, also have a pro-oxidant effect, depending on the concentration and the cellular environment. This review focuses on an analysis of their anti-cancer efficacy against various cancer cell lines via cell cycle arrest (regulation of p53/p21 and CDK/cyclins) and by triggering the mitochondrial intrinsic (Bcl-2/Bax/caspase 9) apoptotic pathway, as well as through the modulation of the signaling pathways (PI3K/Akt, Wnt/ß-catenin, JAK/STAT, MAPK, p53, and NF-ĸB) and their influence on the non-coding RNAs involved in angiogenesis, invasion, migration, and metastasis. The therapeutic potential of quercetin and curcumin is discussed not only on the basis of their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions.

LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes.

In this study we evaluated possible differences in metabolomic profiles of spent embryo culture media (SECM) of human embryos with distinct morphology, karyotype, and implantation outcomes. A total of 153 samples from embryos of patients undergoing in vitro fertilization (IVF) programs were collected and analyzed by HPLC-MS. Metabolomic profiling and statistical analysis revealed clear clustering of day five SECM from embryos with different morphological classes and karyotype. Profiling of day five SECM from embryos with different implantation outcomes showed 241 significantly changed molecular ions in SECM of successfully implanted embryos. Separate analysis of paired SECM samples on days three and five revealed 46 and 29 molecular signatures respectively, significantly differing in culture media of embryos with a successful outcome. Pathway enrichment analysis suggests certain amino acids, vitamins, and lipid metabolic pathways to be crucial for embryo implantation. Differences between embryos with distinct implantation potential are detectable on the third and fifth day of cultivation that may allow the application of culture medium analysis in different transfer protocols for both fresh and cryopreserved embryos. A combination of traditional morphological criteria with metabolic profiling of SECM may increase implantation rates in assisted reproductive technology programs as well as improve our knowledge of the human embryo metabolism in the early stages of development.

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation.

S-glutathionylation and S-nitrosylation are reversible post-translational modifications on the cysteine thiol groups of proteins, which occur in cells under physiological conditions and oxidative/nitrosative stress both spontaneously and enzymatically. They are important for the regulation of the functional activity of proteins and intracellular processes. Connecting link and "switch" functions between S-glutathionylation and S-nitrosylation may be performed by GSNO, the generation of which depends on the GSH content, the GSH/GSSG ratio, and the cellular redox state. An important role in the regulation of these processes is played by Trx family enzymes (Trx, Grx, PDI), the activity of which is determined by the cellular redox status and depends on the GSH/GSSG ratio. In this review, we analyze data concerning the role of GSH/GSSG in the modulation of S-glutathionylation and S-nitrosylation and their relationship for the maintenance of cell viability.

Small Noncoding RNA Signatures for Determining the Developmental Potential of an Embryo at the Morula Stage.

As part of the optimization of assisted reproductive technology programs, the aim of the study was to identify key small noncoding RNA (sncRNA) molecules that participate in maternal-to-zygotic transition and determine development potential and competence to form a healthy fetus. Small RNA deep sequencing followed by quantitative real-time RT-PCR was used to profile sncRNAs in 50 samples of spent culture medium from morula with different development potentials (no potential (degradation/developmental arrest), low potential (poor-quality blastocyst), and high potential (good/excellent quality blastocyst capable of implanting and leading to live birth)) obtained from 27 subfertile couples who underwent in vitro fertilization. We have shown that the quality of embryos at the morula stage is determined by secretion/uptake rates of certain sets of piRNAs and miRNAs, namely hsa_piR_011291, hsa_piR_019122, hsa_piR_001311, hsa_piR_015026, hsa_piR_015462, hsa_piR_016735, hsa_piR_019675, hsa_piR_020381, hsa_piR_020485, hsa_piR_004880, hsa_piR_000807, hsa-let-7b-5p, and hsa-let-7i-5p. Predicted gene targets of these sncRNAs included those globally decreased at the 8-cell-morula-blastocyst stage and critical to early embryo development. We show new original data on sncRNA profiling in spent culture medium from morula with different development potential. Our findings provide a view of a more complex network that controls human embryogenesis at the pre-implantation stage. Further research is required using reporter analysis to experimentally confirm interactions between identified sncRNA/gene target pairs.

The role of abnormal hypermethylation of the HOXA10 and HOXA11 promoters in implantation failures in IVF programs.

Objective: The objective of this study is to investigate the association between methylation levels of HOXA10 and HOXA11 promoters, clinical parameters, and implantation outcomes after in vitro fertilization-embryo transfer (IVT-ET) cycles in women with repeated implantation failures and tubal infertility. Methods: Endometrium samples were collected from 34 women during implantation window before IVF-ET cycle to assess methylation status of HOXA10 and HOXA11 promoters using bisulfite sequencing. All participants had a tubal factor of infertility and at least two implantation failures in the anamnesis. A logistic regression model was used to predict the implantation outcome depending on methylation status and clinical parameters. Results: The methylation of CpG-islands of HOXA10 and HOXA11 promoters was identified in 76.5 and 100% of participants, respectively. The median methylation levels did not differ significantly between the groups with different implantation outcomes, but a logistic regression model based on HOXA10 and HOXA11 methylation and clinical parameters allowed to classify the implantation outcomes with the total percentage of correct predictions of 85.19%. Conclusions: Abnormal methylation levels of the HOXA10 and HOXA11 promoters were found in the endometrium of women with tubal infertility and repeated implantation failures. The findings suggest that methylation status could be an important factor of implantation failure during IVF-ET cycles.

Cell-Free, Embryo-Specific sncRNA as a Molecular Biological Bridge between Patient Fertility and IVF Efficiency.

Small noncoding RNAs (sncRNAs) are key regulators of the majority of human reproduction events. Understanding their function in the context of gametogenesis and embryogenesis will allow insight into the possible causes of in vitro fertilization (IVF) implantation failure. The aim of this study was to analyze the sncRNA expression profile of the spent culture media on day 4 after fertilization and to reveal a relationship with the morphofunctional characteristics of gametes and resultant embryos, in particular, with the embryo development and implantation potential. Thereto, cell-free, embryo-specific sncRNAs were identified by next generation sequencing (NGS) and quantified by reverse transcription coupled with polymerase chain reaction (RT-PCR) in real-time. Significant differences in the expression level of let-7b-5p, let-7i-5p, piR020401, piR16735, piR19675, piR20326, and piR17716 were revealed between embryo groups of various morphological gradings. Statistically significant correlations were found between the expression profiles of piR16735 and piR020401 with the oocyte-cumulus complex number, let-7b-5p and piR020401 with metaphase II oocyte and two pronuclei embryo numbers, let-7i-5p and piR20497 with the spermatozoid count per milliliter of ejaculate, piR19675 with the percentage of linearly motile spermatozoids, let-7b-5p with the embryo development grade, and let-7i-5p with embryo implantation. According to partial least squares discriminant analysis (PLS-DA), the expression levels of let-7i-5p (Variable Importance in Projection score (VIP) = 1.6262), piR020401 (VIP = 1.45281), and piR20497 (VIP = 1.42765) have the strongest influences on the implantation outcome.

Cell and genetic predictors of human blastocyst hatching success in assisted reproduction.

The aim was to identify cell and genetic predictors of human blastocyst hatching success in assisted reproduction programmes via a prospective case-control study. Blastocysts, donated by couples in assisted reproduction programmes were used. Hatching success assessment was performed after 144-146 h post-fertilization. The mRNA expression levels of cathepsin V (CTSV), GATA-binding protein 3 (GATA3) and human chorionic gonadotropin beta subunit 3, 5, 7 and 8 (CGB) genes were detected by quantitative real-time polymerase chain reaction. The odds ratio (OR) of hatching due to zona pellucida (ZP) thickness, oocyte and sperm quality, embryo quality and mRNA expression of CTSV, GATA3 and CGB genes in blastocysts was determined. From 62 blastocysts included in the study, 47 (75.8%) were unable to hatch spontaneously. The ZP thickening, and oocyte and sperm quality did not affect human blastocyst ability to hatch, except the combination of cytoplasmic and extracytoplasmic oocyte dysmorphisms (OR = 1.25; 95% confidence interval = 1.08, 1.45). Hatching-capable blastocysts had higher Gardner scale grade and mRNA expression of CTSV, GATA3 and CGB genes than hatching-incapable blastocysts. The human blastocyst hatching success depends on the blastocyst Gardner grade, but not on ZP and gamete quality. Blastocyst development was regulated by CTSV, GATA3 and CGB gene expression.

Editorial for the Special Issue on Advanced Thin-Films: Design, Fabrication and Applications.

The application scope of basic functional materials can be expanded through the creation of thin films due to the emergence of new unique properties of film materials that differ from their bulk analogues [...].

Stress Biomarkers Transferred Into the Female Reproductive Tract by Seminal Plasma Are Associated with ICSI Outcomes.

This study aimed to determine whether male stress is related to seminal stress biomarkers and pregnancy achievement in women exposed to their partner's seminal plasma (SP) in the intracytoplasmic sperm injection (ICSI) cycle. In this pilot prospective study, 20 couples undergoing ICSI, as well as 5 fertile sperm donors and 10 saliva donors, were investigated. Women were exposed to their partner's SP via unprotected sexual intercourse during the ICSI cycle and intravaginal application on the day of ovum pick-up (Day-OPU). Semen samples were collected from male partners by masturbation on the Day-OPU. Saliva and serum samples were collected prior to masturbation. Body fluids were frozen at - 80 °C until assayed. Biomarkers of activity of the sympathetic adrenomedullary axis (salivary alpha-amylase and adrenaline), sympathetic neural axis (noradrenaline and dopamine), hypothalamic-pituitary-adrenal (HPA) system (cortisol), and immune system (C-reactive protein and interleukin (IL)-18) were estimated to examine their association with SP composition and clinical pregnancy achievement. The clinical pregnancy rate was 45.0%. In the unsuccessful ICSI group, blunted levels of salivary and serum cortisol were found compared to the successful ICSI group and the fertile sperm donors. With regard to seminal markers, decreased cortisol level and elevated noradrenaline, noradrenaline/cortisol ratio, and lL-18 levels were strongly associated with ICSI failure (areas under the ROC curves were, 0.813, 0.848, 0.899, and 0.828, respectively). These findings confirm that stress response systems activity affects SP composition, which in turn is associated with ICSI outcomes in women exposed to their partner's SP during an ICSI cycle.

Characteristics of the Follicular Fluid Extracellular Vesicle Molecular Profile in Women in Different Age Groups in ART Programs.

The aim of this study was to investigate the molecular composition of follicular fluid (FF) extracellular vesicles (EVs) in women of different reproductive ages and its possible relationship to sperm fertilizing ability. FF EVs were obtained by differential centrifugation. The concentration and size distribution of FF EVs were analyzed by nanoparticle tracking analysis. The lipidome and proteome were analyzed by liquid chromatography-mass spectrometry. The isolated FF EVs had a variety of shapes and sizes; their concentration and size distribution did not differ significantly between the age groups. In women younger than 35 years, the concentration of vesicular progesterone was 6.6 times higher than in women older than 35 years, and the total levels of the main lipid classes were increased in younger women. A proteomic analysis revealed that not only FF EV-specific proteins, but also proteins involved in sperm activation were present. New data were obtained on the composition of FF EVs, confirming their importance as molecular indicators of age-related changes in the female reproductive system. In addition, these results shed light on the possible interaction between the FF EVs of women in different age groups and male germ cells. Therefore, studying the transcriptomic and metabolomic profile of FF EVs may be a crucial approach to evaluate the efficacy of ART.

Performance Enhancement of Ce0.8Sm0.2O1.9-Supported SOFC by Electrophoretic Formation of Modifying BaCe0.8Sm0.2O3 and Ce0.8Sm0.1Pr0.1O1.9 Layers.

The strategy to increase the performance of the single solid oxide fuel cell (SOFC) with a supporting membrane of Ce0.8Sm0.2O1.9 (SDC) electrolyte has been implemented in this study by introducing a thin anode barrier layer of the BaCe0.8Sm0.2O3 + 1 wt% CuO (BCS-CuO) electrolyte and, additionally, a modifying layer of a Ce0.8Sm0.1Pr0.1O1.9 (PSDC) electrolyte. The method of electrophoretic deposition (EPD) is used to form thin electrolyte layers on a dense supporting membrane. The electrical conductivity of the SDC substrate surface is achieved by the synthesis of a conductive polypyrrole sublayer. The kinetic parameters of the EPD process from the PSDC suspension are studied. The volt-ampere characteristics and power output of the obtained SOFC cells with the PSDC modifying layer on the cathode side and the BCS-CuO blocking layer on the anode side (BCS-CuO/SDC/PSDC) and with a BCS-CuO blocking layer on the anode side (BCS-CuO/SDC) and oxide electrodes have been studied. The effect of increasing the power output of the cell with the BCS-CuO/SDC/PSDC electrolyte membrane due to a decrease in the ohmic and polarization resistances of the cell is demonstrated. The approaches developed in this work can be applied to the development of SOFCs with both supporting and thin-film MIEC electrolyte membranes.