Bartlettmonrad9876

Reducing anode catalyst layer proton- and electron-transport resistances in polymer electrolyte membrane water electrolyzers is critical to improving its performance and maximizing catalyst utilization at high current density. A hydrogen pump technique is adapted to measure the protonic conductivity of IrO x -based catalyst layers. The protonic resistance of the catalyst layer is obtained by subtracting the protonic resistance of an assembly of two NRE211 membranes hot-pressed together from an assembly of two NRE211 membranes with an IrO x intermediate layer. The through-plane and in-plane electronic conductivities were also measured using two- and four-probe methods, respectively. Using these techniques, the protonic and electronic conductivities of the IrO x catalyst layers with varying Nafion loading were measured. The results show that the limiting charge-transport phenomena in the IrO x catalyst layer can be either proton or electron transport, depending on the ionomer loading in the catalyst layer. These results are validated by numerical simulation, as well as by comparison to the high-frequency resistance of an electrolyzer with the same layer.Cellular reprogramming is an emerging strategy for delaying the aging processes. However, a number of challenges, including the impaired genome integrity and decreased pluripotency of induced pluripotent stem cells (iPSCs) derived from old donors, may hinder their potential clinical applications. The longevity gene, Sirtuin 6 (SIRT6), functions in multiple biological processes such as the maintenance of genome integrity and the regulation of somatic cell reprogramming. Here, for the first time, we demonstrate that MDL-800, a recently developed selective SIRT6 activator, improved genomic stability by activating two DNA repair pathways-nonhomologous end joining (NHEJ) and base excision repair (BER) in old murine-derived iPSCs. More interestingly, we found that pretreating old murine iPSCs, which normally exhibit a restricted differentiation potential, with MDL-800 promoted the formation of teratomas comprised of all three germ layers and robustly stimulated chimera generation. Our findings suggest that pharmacological activation of SIRT6 holds great promise in treating aging-associated diseases with iPSC-based cell therapy.

Amyotrophic lateral sclerosis (ALS) is a multisystem disorder associated with motor impairment and behavioral/cognitive involvement. We examined decision-making features and changes in the neural hub network in patients with ALS using a probabilistic reversal learning task and resting-state network analysis, respectively.

Ninety ALS patients and 127 cognitively normal participants performed this task. Data from 62 ALS patients and 63 control participants were fitted to a Q-learning model.

ALS patients had anomalous decision-making features with little shift in choice until they thought the value of the two alternatives had become equal. The quantified parameters (Pαβ) calculated by logistic regression analysis with learning rate and inverse temperature well represented the unique choice pattern of ALS patients. Resting-state network analysis demonstrated a strong correlation between Pαβ and decreased degree centrality in the anterior cingulate gyrus and frontal pole.

Altered decision-making in ALS patients may be related to the decreased hub function of medial prefrontal areas.

Altered decision-making in ALS patients may be related to the decreased hub function of medial prefrontal areas.

The present study had two aims (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death.

In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by pre-determined research protocol). All participants were successfully matched 11 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4%±4.3 vs. 18.5%±3.0, P<0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0±0.4 vs. 2.6±0.5, P<0.001), and RV strain (19.8±5.9 vs. 24.2±6.5, P=0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow-up (median 40days), 25 COVID-19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR)=1.18, 95% confidence interval (CI) [1.07-1.31], P=0.002, per 1mm decrease], RV strain (HR=1.64, 95%CI[1.02;2.66], P=0.043, per 1% decrease) and GLS (HR=1.20, 95%CI[1.07-1.35], P=0.002, per 1% decrease) were significantly associated with COVID-19-related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease.

RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.

RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.

Poverty is characterized by a scarcity of resources and a threat of certain stereotypes. However, the effects of stereotype threat are largely dependent on various factors, both negative and positive. Few psychophysiological studies have studied the effects of poverty stereotype threats on inhibition ability in wealth and impoverished individuals.

To fill this gap in the literature, this study used the event-related potential (ERP) technique to explore the brain mechanisms associated with stereotype threat in 135 participants.

Behavioral results showed that the rich group (participants from higher-income families) had better inhibition ability than the impoverished group (participants from lower-income families), with significantly shorter reaction time and significantly greater accuracy for poverty-related stimuli when in the nonthreat condition. Additionally, poverty stereotype threat could improve performance of the impoverished group for poverty-related stimuli. The electrophysiological results showed significantly larger P3 mean amplitude and significantly longer P3 latency in the rich group than the impoverished group in the nonthreat condition. Although no significant between-group differences were found in the threat condition, the results show that the effect of poverty stereotype threat varies with different income-level persons, for both behavioral and P3 data.

These findings suggest that impoverished people have worse inhibition abilities. Further, poverty stereotype threat has different effects on people according to their income level and could help to explain irrational consumption behaviors in people.

These findings suggest that impoverished people have worse inhibition abilities. Further, poverty stereotype threat has different effects on people according to their income level and could help to explain irrational consumption behaviors in people.Long noncoding RNA NUTM2A-AS1 has been shown to be dysregulated in non-small cell lung carcinoma. To date, it is unclear whether NUTM2A-AS1 plays a role in gastric cancer progression. The purpose of this study is to elucidate the molecular mechanism of the role of NUTM2A-AS1 in gastric cancer. mRNA and protein levels were measured by RT-qPCR and western blot methods. Invasion ability was examined by transwell assay. Cell viability was determined by MTT assay. Dual-luciferase assay, RNA pull down, and RNA immunoprecipitation were used to confirm direct binding of between miR-376a and NUTM2A-AS1 or TET1. Xenografting tumor assay and TCGA analysis showed the contributory role of NUTM2A-AS1 in vivo and human clinical setting. Our results suggested that NUTM2A-AS1 promoted cell viability, invasion, and drug resistance of gastric cancer cells, which was largely rescued by miR-376a. More interestingly, TET1 and HIF-1A were negatively regulated by miR-376a. TET1 could interact with HIF-1A to modulate PD-L1. Finally, we revealed that PD-L1 was key to NUTM2A-AS1- and miR-376a-mediated tumorigenesis and drug resistance. In summary, our conclusions facilitate us understand the underlying mechanism and develop novel treatment strategy for gastric cancer.Few studies have explored HER2 status in cervical adenocarcinoma, particularly in the gastric-type adenocarcinoma (GAC), a nonhuman-papillomavirus-related subtype with poor clinical outcomes. In this study, we investigated HER2 expression and amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 209 well annotated cervical adenocarcinomas diagnosed using the International Endocervical Adenocarcinoma Criteria and Classification. IHC identified HER2 protein expression in 57.4% (123/209) of adenocarcinomas, of which 62 were IHC 1+ (negative), 38 2+ (equivocal) and 23 3+ (positive). HER2 amplification was found in 13 cases (6.2%) including 10 with IHC 3+ and 3 with IHC 2+. Among all the major histotypes of cervical adenocarcinoma, HER2 amplification was most common in GAC cases with a frequency of 14.7% (5/34). Moreover, HER2 amplification was more frequently associated with 2018 International Federation of Gynecology & Obstetrics (FIGO) stage III/IV, perineural involvement and ovarian spread (p  less then  0.05) while IHC 3+ was more common in patients with lymphovascular invasion and ovarian involvement (p  less then  0.05). Survival analysis indicated that FIGO stage III/IV, GAC, and p53 overexpression were associated with poor disease-specific survival and tumor recurrence (p  less then  0.05). In conclusion, HER2 amplification was present in a subset of adenocarcinomas, and more common in GAC, pointing to a potential benefit from trastuzumab treatment. HER2 overexpression does not identify gene amplification status in cervical adenocarcinoma; therefore, FISH is suggested for both IHC positive and equivocal cases. Further investigation on more cases with longer follow-up times is required to consolidate these findings.Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Guadecitabine Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drug therapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine.