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1.
Proc Natl Acad Sci U S A ; 121(25): e2400546121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38857407

ABSTRACT

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

2.
Proc Natl Acad Sci U S A ; 120(51): e2312876120, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38085783

ABSTRACT

Electrochemical synthesis of valuable chemicals and feedstocks through carbon dioxide (CO2) reduction in acidic electrolytes can surmount the considerable CO2 loss in alkaline and neutral conditions. However, achieving high productivity, while operating steadily in acidic electrolytes, remains a big challenge owing to the severe competing hydrogen evolution reaction. Here, we show that vertically grown bismuth nanosheets on a gas-diffusion layer can create numerous cavities as electrolyte reservoirs, which confine in situ-generated hydroxide and potassium ions and limit inward proton diffusion, producing locally alkaline environments. Based on this design, we achieve formic acid Faradaic efficiency of 96.3% and partial current density of 471 mA cm-2 at pH 2. When operated in a slim continuous-flow electrolyzer, the system exhibits a full-cell formic acid energy efficiency of 40% and a single pass carbon efficiency of 79% and performs steadily over 50 h. We further demonstrate the production of pure formic acid aqueous solution with a concentration of 4.2 weight %.

3.
J Am Chem Soc ; 145(21): 11537-11543, 2023 May 31.
Article in English | MEDLINE | ID: mdl-37192535

ABSTRACT

Here, we report a diagnostic framework for elucidating the mechanisms of photoredox-based hydrogen isotope exchange (HIE) reactions based on hydrogen/deuterium (H/D) fractionation. Traditional thermal HIE methods generally proceed by reversible bond cleavage and bond reformation steps that share a common transition state. However, bond cleavage and bond reformation in light-driven HIE reactions can proceed via multiple, non-degenerate sets of elementary steps, complicating both mechanistic analysis and attendant optimization efforts. Building on classical treatments of equilibrium isotope effects, the fractionation method presented here extracts information regarding the nature of the key bond-forming and bond-breaking steps by comparing the extent of deuterium incorporation into an exchangeable C-H bond in the substrate relative to the H/D isotopic ratio of a solvent reservoir. We show that the extent of fractionation is sensitive to the mechanism of the exchange process and provides a means to distinguish between degenerate and non-degenerate mechanisms for isotopic exchange. In model systems, the mechanisms implied by the fractionation method align with those predicted by thermochemical considerations. We then employed the method to study HIE reactions whose mechanisms are ambiguous on thermodynamic grounds.

4.
J Am Chem Soc ; 145(44): 24338-24348, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37880928

ABSTRACT

Carbon-carbon coupling electrochemistry on a conventional copper (Cu) catalyst still undergoes low selectivity among many different multicarbon (C2+) chemicals, posing a grand challenge to achieve a single C2+ product. Here, we demonstrate a laser irradiation synthesis of a gerhardtite mineral, Cu2(OH)3NO3, as a catalyst precursor to make a Cu catalyst with abundant stacking faults under reducing conditions. Such structural perturbation modulates electronic microenvironments of Cu, leading to improved d-electron back-donation to the antibonding orbital of *CO intermediates and thus strengthening *CO adsorption. With increased *CO coverage on the defect-rich Cu, we report an acetate selectivity of 56 ± 2% (compared to 31 ± 1% for conventional Cu) and a partial current density of 222 ± 7 mA per square centimeter in CO electroreduction. When run at 400 mA per square centimeter for 40 h in a flow reactor, this catalyst produces 68.3 mmol of acetate throughout. This work highlights the value of a Cu-containing mineral phase in accessing suitable structures for improved selectivity to a single desired C2+ product.

5.
J Neuroinflammation ; 20(1): 55, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36864466

ABSTRACT

BACKGROUND: Periodontitis is closely associated with the pathogenesis of Alzheimer's disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg. METHODS: To explore the influence of Pg on cognitive function, neuropathology and immune balance in vivo, 5xFAD mice were treated with live Pg by oral gavage, three times a week for 1 month. The cells of peripheral blood, spleen and bone marrow from 5xFAD mice were treated with Pg to detect the proportional and functional alterations of mMDSCs in vitro. Next, exogenous mMDSCs were sorted from wild-type healthy mice and intravenously injected into 5xFAD mice that were infected with Pg. We used behavioral tests, flow cytometry and immunofluorescent staining to evaluate whether exogenous mMDSCs could ameliorate the cognitive function, immune homeostasis and reduce neuropathology exacerbated by Pg infection. RESULTS: Pg exacerbated cognitive impairment in 5xFAD mice, with the deposition of amyloid plaque and increased number of microglia in the hippocampus and cortex region. The proportion of mMDSCs decreased in Pg-treated mice. In addition, Pg reduced the proportion and the immunosuppressive function of mMDSCs in vitro. Supplement of exogenous mMDSCs improved the cognitive function, and enhanced the proportions of mMDSCs and IL-10+ T cells of 5xFAD mice infected with Pg. At the same time, supplement of exogenous mMDSCs increased the immunosuppressive function of endogenous mMDSCs while decreased the proportions of IL-6+ T cells and IFN-γ+ CD4+ T cells. In addition, the deposition of amyloid plaque decreased while the number of neurons increased in the hippocampus and cortex region after the supplement of exogenous mMDSCs. Furthermore, the number of microglia increased with an increase in the proportion of M2 phenotype. CONCLUSIONS: Pg can reduce the proportion of mMDSCs, induce immune-overreaction, and exacerbate the neuroinflammation and cognitive impairment in 5xFAD mice. Supplement of exogenous mMDSCs can reduce the neuroinflammation, immune imbalance and cognitive impairment in 5xFAD mice infected with Pg. These findings indicate the mechanism of AD pathogenesis and Pg-mediated promotion of AD, and provide a potential therapeutic strategy for AD patients.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Myeloid-Derived Suppressor Cells , Animals , Mice , Monocytes , Neuroinflammatory Diseases , Porphyromonas gingivalis , Plaque, Amyloid , Alzheimer Disease/complications
6.
J Nurs Scholarsh ; 55(1): 304-318, 2023 01.
Article in English | MEDLINE | ID: mdl-36121127

ABSTRACT

OBJECTIVE: To explore the effectiveness of a nurse-led mobile health (mHealth) intervention to prevent excessive gestational weight gain (GWG) in overweight and obese women. METHODS: A randomized controlled trial with an experimental study design. Ninety-two pregnant women with body mass index (BMI) ≥25 kg/m2 at less than 17 weeks gestation were recruited from two prenatal clinics in northern Taiwan from January to June 2020. The experimental group used the MyHealthyWeight (MHW) app and a wearable activity tracker (WAT), and the controls received standard antenatal treatments with no mHealth-based elements. Two hospital follow-up visits were scheduled at 24-26 weeks in the second trimester and 34-36 weeks in the third trimester. A generalized estimating equation (GEE) was used to examine the trajectories and the effectiveness of mHealth on GWG. RESULTS: No difference in GWG was found between the intervention and control groups at baseline (p > 0.05). The GWG trajectory in the entire cohort of women with obesity exhibited a quadratic pattern (ß = 1.8, 95% confidence interval [CI] = 1.27-2.32), and intervention participants' weekly GWG was gained significantly lower than their controls in the second trimester (p < 0.05). Throughout the pregnancy, the mHealth intervention group had a significantly lower proportion of individuals who exceeded their GWG in both total (21.6% vs. 32.6%) and weekly weight gain (first trimester = 58.7% vs. 65.2%; second trimester = 45% vs. 67.4%; third trimester = 48.6% vs. 55.1%). In particular, among obese women in the third trimester, those in the intervention group gained less gestational weight than their controls. The adjusted body weight difference was 5.44 kg (p = 0.023), signifying the total GWG difference (3.30 vs. 8.74 kg) between the means of the two groups. The GEE model indicated that obese women who were aged 35 years, had prepregnancy exercise habits, perceived self-efficacy of diet, and more physical activity tended to have low GWG (p < 0.05). CONCLUSIONS: The nurse-led mHealth-based intervention shows promising results in significantly preventing excessive GWG among high-BMI women. More effectiveness was found among the obese subgroup. CLINICAL RELEVANCE: The mHealth-based intervention would be successfully implemented by nurses to help high-BMI women maintain their optimal body weight and promote healthy behavioral changes, particularly in diet and physical activity during pregnancy.


Subject(s)
Gestational Weight Gain , Mobile Applications , Telemedicine , Female , Pregnancy , Humans , Overweight/therapy , Nurse's Role , Obesity/therapy , Weight Gain , Telemedicine/methods , Body Mass Index
7.
Int J Mol Sci ; 24(3)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36769168

ABSTRACT

Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE.


Subject(s)
Pleural Effusion , Tuberculosis , Humans , Vascular Endothelial Growth Factor A/genetics , Toll-Like Receptor 2/genetics , Vascular Endothelial Growth Factors
8.
Curr Psychol ; 42(7): 5462-5469, 2023.
Article in English | MEDLINE | ID: mdl-34075285

ABSTRACT

The relationship between mindfulness and well-being and ill-being has been demonstrated to a great extent. In sports, the fulfillment of individuals' basic psychological needs depends mostly on support from others, such as that from a coach in a sports team context. However, a possible way for individuals to fulfill their basic psychological needs is by enhancing mindfulness rather than depending on others. Therefore, building on SDT and mindfulness, this study examines the mediating effect of basic psychological needs on mindfulness to predict subjective vitality and athlete burnout in professional golfers. The participants were 120 golfers (47% females), with a mean age and golf experience of 22.28 and 9.48 years, respectively. The association between mindfulness and subjective vitality was partially mediated by the need for autonomy and relatedness. By contrast, the association between mindfulness and burnout was partially mediated by the need for competence and relatedness, thus supporting our mediation analysis. Overall, the study highlights mindfulness as a potential mechanism to ensure the fulfillment of basic psychological needs in golf training, which could enhance golfers' subjective vitality and reduce the occurrence of burnout.

9.
J Am Chem Soc ; 144(1): 259-269, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-34962375

ABSTRACT

The electrosynthesis of valuable multicarbon chemicals using carbon dioxide (CO2) as a feedstock has substantially progressed recently but still faces considerable challenges. A major difficulty lines in the sluggish kinetics of forming carbon-carbon (C-C) bonds, especially in neutral media. We report here that oxide-derived copper crystals enclosed by six {100} and eight {111} facets can reduce CO2 to multicarbon products with a high Faradaic efficiency of 74.9 ± 1.7% at a commercially relevant current density of 300 mA cm-2 in 1 M KHCO3 (pH ∼ 8.4). By combining the experimental and computational studies, we uncovered that Cu(100)/Cu(111) interfaces offer a favorable local electronic structure that enhances *CO adsorption and lowers C-C coupling activation energy barriers, performing superior to Cu(100) and Cu(111) surfaces, respectively. On this catalyst, no obvious degradation was observed at 300 mA cm-2 over 50 h of continuous operation.

10.
Nature ; 537(7622): 694-697, 2016 Sep 29.
Article in English | MEDLINE | ID: mdl-27654918

ABSTRACT

A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as ß-farnesene (C15H24), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO2-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.


Subject(s)
Bioreactors , Carbon/metabolism , Metabolic Engineering , Saccharomyces cerevisiae/metabolism , Terpenes/metabolism , Acetyl Coenzyme A/biosynthesis , Acetyl Coenzyme A/metabolism , Adenosine Triphosphate/metabolism , Biosynthetic Pathways , Carbohydrate Metabolism , Carbon Dioxide/metabolism , Cytosol/metabolism , Fermentation , Oxidation-Reduction , Oxygen/metabolism , Saccharomyces cerevisiae/enzymology , Sesquiterpenes/metabolism
11.
Int J Mol Sci ; 23(19)2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36232674

ABSTRACT

Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin's effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3ß (GSK3ß), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3ß and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.


Subject(s)
Glycyrrhiza , P-Selectin , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Adenosine Triphosphate/metabolism , Animals , Blood Platelets/metabolism , Collagen/metabolism , Flavonoids/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Isoflavones , Mice , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , P-Selectin/metabolism , Phenols , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phospholipase C gamma/metabolism , Phosphorylation , Platelet Activation , Platelet Aggregation , Protein Kinase C/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Thrombin/metabolism , Thromboxanes/metabolism
12.
Molecules ; 27(2)2022 Jan 12.
Article in English | MEDLINE | ID: mdl-35056795

ABSTRACT

Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from Tetradium ruticarpum, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1-6 µM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases.


Subject(s)
Fibrinolytic Agents/pharmacology , Indole Alkaloids/pharmacology , NF-kappa B/metabolism , Nitriles/pharmacology , Quinazolines/pharmacology , Sulfones/pharmacology , Thrombosis/drug therapy , Thrombosis/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Disease Models, Animal , Fibrinolytic Agents/therapeutic use , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Free Radicals/antagonists & inhibitors , Humans , I-kappa B Kinase/antagonists & inhibitors , Imidazoles/pharmacology , Imidazoles/therapeutic use , Indole Alkaloids/therapeutic use , Male , Mice, Inbred ICR , NF-kappa B/antagonists & inhibitors , Nitriles/therapeutic use , P-Selectin/metabolism , Platelet Activation/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , Pulmonary Embolism/metabolism , Pyridines/pharmacology , Pyridines/therapeutic use , Quinazolines/therapeutic use , Sulfones/therapeutic use , Transcription Factor RelA/metabolism
13.
Curr Psychol ; : 1-14, 2022 Oct 22.
Article in English | MEDLINE | ID: mdl-36313583

ABSTRACT

Academic engagement in recent years has become the focus of determining student learning and achievement. However,despite this growing awareness that has revolutionized academic policies and educational approaches, literature on engagement in the academic context is still in its infancy. This study seeks to remedy this through the confirmation of the Utrecht Work Engagement Scale for Students' (UWES-S) promising psychometric properties and by providing empirical evidence on the relationship between academic engagement, personality traits, and social media addiction, a determinant that has yet to be explored. Our findings indicate that of the five personality traits analyzed, agreeableness had the strongest negative correlation with academic engagement, and perhaps equally as striking is the positive, albeit insignificant, association between social media and academic engagement. Furthermore, the most informative and least informative items for academic engagement were identified using IRT analysis. Finally, this study also addresses several gaps in the literature by determining that the one-factor construct of the UWES-S is an adequate measure of academic engagement compared to its three-factor counterpart and by demonstrating the measurement invariance of the UWES-S across gender, class year, and academic major in our sample of Taiwanese undergraduates.

14.
BMC Bioinformatics ; 22(Suppl 5): 148, 2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34749637

ABSTRACT

BACKGROUND: The prevalence of chronic disease is growing in aging societies, and artificial-intelligence-assisted interpretation of macular degeneration images is a topic that merits research. This study proposes a residual neural network (ResNet) model constructed using uniform design. The ResNet model is an artificial intelligence model that classifies macular degeneration images and can assist medical professionals in related tests and classification tasks, enhance confidence in making diagnoses, and reassure patients. However, the various hyperparameters in a ResNet lead to the problem of hyperparameter optimization in the model. This study employed uniform design-a systematic, scientific experimental design-to optimize the hyperparameters of the ResNet and establish a ResNet with optimal robustness. RESULTS: An open dataset of macular degeneration images ( https://data.mendeley.com/datasets/rscbjbr9sj/3 ) was divided into training, validation, and test datasets. According to accuracy, false negative rate, and signal-to-noise ratio, this study used uniform design to determine the optimal combination of ResNet hyperparameters. The ResNet model was tested and the results compared with results obtained in a previous study using the same dataset. The ResNet model achieved higher optimal accuracy (0.9907), higher mean accuracy (0.9848), and a lower mean false negative rate (0.015) than did the model previously reported. The optimal ResNet hyperparameter combination identified using the uniform design method exhibited excellent performance. CONCLUSION: The high stability of the ResNet model established using uniform design is attributable to the study's strict focus on achieving both high accuracy and low standard deviation. This study optimized the hyperparameters of the ResNet model by using uniform design because the design features uniform distribution of experimental points and facilitates effective determination of the representative parameter combination, reducing the time required for parameter design and fulfilling the requirements of a systematic parameter design process.


Subject(s)
Artificial Intelligence , Macular Degeneration , Disease Progression , Humans , Macular Degeneration/diagnostic imaging , Neural Networks, Computer , Signal-To-Noise Ratio
15.
J Cell Physiol ; 236(8): 5646-5663, 2021 08.
Article in English | MEDLINE | ID: mdl-33432662

ABSTRACT

This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4-overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C-terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4-mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology.


Subject(s)
Citrullination/drug effects , Homeostasis/physiology , Ornithine Decarboxylase Inhibitors/pharmacology , Ornithine Decarboxylase/metabolism , Polyamines/metabolism , Carrier Proteins/metabolism , Citrullination/physiology , Homeostasis/drug effects , Humans , Ornithine Decarboxylase Inhibitors/metabolism , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism
16.
J Am Chem Soc ; 143(21): 8011-8021, 2021 06 02.
Article in English | MEDLINE | ID: mdl-33913717

ABSTRACT

Copper is currently the material with the most promise as catalyst to drive carbon dioxide (CO2) electroreduction to produce value-added multicarbon (C2+) compounds. However, a copper catalyst on a carbon-based gas diffusion layer electrode often has poor stability-especially when performing at high current densities-owing to electrolyte flooding caused by the hydrophobicity decrease of the gas diffusion layer during operation. Here, we report a bioinspired copper catalyst on a gas diffusion layer that mimics the unique hierarchical structuring of Setaria's hydrophobic leaves. This hierarchical copper structure endows the CO2 reduction electrode with sufficient hydrophobicity to build a robust gas-liquid-solid triple-phase boundary, which can not only trap more CO2 close to the active copper surface but also effectively resist electrolyte flooding even under high-rate operation. We consequently achieved a high C2+ production rate of 255 ± 5.7 mA cm-2 with a 64 ± 1.4% faradaic efficiency, as well as outstanding operational stability at 300 mA cm-2 over 45 h in a flow reactor, largely outperforming its wettable copper counterparts.

17.
Mol Phylogenet Evol ; 155: 106999, 2021 02.
Article in English | MEDLINE | ID: mdl-33130300

ABSTRACT

East Asia has highly diverse and endemic biota due to its complex geological and climatic history and its diversified topography. The continental and insular distributions of land snail genus Acusta in East Asia provide a good opportunity to compare the evolutionary processes in this group under different biogeographical conditions. In this study, we inferred the evolutionary history of the land snail genus Acusta by a molecular phylogeny and investigated how the palaeogeographic events shaped species diversity and the distribution of the Acusta genus within the island arc. A concatenated dataset generated from sequences of one nuclear (ITS2) and two mitochondrial (16S, COI) gene fragments, include most of nominal taxa of the genus, four related species and one outgroup. We constructed the phylogeny and the evolutionary history of the genus through maximum-likelihood and Bayesian inference methods, using a Bayesian molecular clock and ancestral range estimation. Our results suggested that currently recognized species in Acusta are polyphyletic. The traditionally accepted concept of the affinity of Acusta and Bradybaena is not supported. The hypothesis of colonization via land bridges during the Pleistocene glaciations for the biota of East Asian islands is not supported. Instead, the origin and diversification of the genus Acusta was dated to the late Miocene-Pliocene from an area around North and Northeast China to South China and East Asian islands Three major evolutionary lineages were identified. Two of the major lineages demonstrate distinct evolutionary histories, as sympatric speciation is the major speciation process for the continental clade, while the insular clade originated from founder events. Taiwan functioned as an important source of diversification for species on the East Asian islands possibly through passive dispersal of different mechanisms. The sea level fluctuations caused by the Pleistocene glacial cycles play a role in the subsequent dispersion and diversification of species of the continental clade, such as the more recent range expansion of A. redfieldi from South China to Taiwan and Japan.


Subject(s)
Biodiversity , Phylogeography , Snails/classification , Animals , Bayes Theorem , Calibration , Cell Nucleus/genetics , Asia, Eastern , Genes, Mitochondrial , Islands , Phylogeny , Snails/genetics , Time Factors
18.
J Interv Cardiol ; 2021: 1195613, 2021.
Article in English | MEDLINE | ID: mdl-35035305

ABSTRACT

OBJECTIVES: Minimally invasive coronary artery bypass grafting (MICS CABG) has emerged as an alternative treatment for patients with multi-vessel coronary artery disease, but there are certain surgical challenges inherent in the adoption of this approach. The present study was conducted to provide insight regarding the outcomes associated with our first 118 cases, to discuss the surgical difficulties encountered in these patients, and to outline the potential countermeasures. METHODS: Between January 2017 and January 2020, 118 patients underwent multi-vessel MICS CABG. These patients were stratified into two groups based upon whether they did or did not experience surgical challenges, and early clinical outcomes were compared between these groups to assess the incidence of technical difficulties and associated factors. RESULTS: Surgical challenges arose in 38 of the 118 cases in this study, including 13 cases of exposure-related difficulties, 11 cases of proximal anastomosis-related difficulties, 15 cases of distal anastomosis-related difficulties, 4 cases of LITA-related difficulties, and 3 cases of lung-related difficulties. Relative to the other 80 patients, those patients for whom intraoperative technical challenges arose experience significant increases in operative duration (4.94 ± 0.89 vs. 5.59 ± 1.11 h, P=0.001), intraoperative blood loss (667 ± 313 vs. 892 ± 532 mL, P=0.005), length of the ICU admission (17.59 ± 3.51 vs. 22.59 ± 17.31 h, P=0.015), and the duration of postoperative hospitalization (5.96 ± 1.23 vs. 6.71 ± 1.92 days, P=0.012). There were no significant differences between these groups with respect to the mean graft number, major complications such as stroke or organ dysfunction, or one-year graft patency. CONCLUSIONS: There is a substantial learning curve associated with performing off-pump MICS CABG to treat multi-vessel disease. Surgical challenges encountered during this procedure may increase the operative duration, intraoperative blood loss, ICU admission, and the duration of postoperative hospitalization. However, these issues do not appear to compromise the efficacy of complete revascularization, and early clinical outcomes associated with this procedure remain acceptable.


Subject(s)
Coronary Artery Disease , Minimally Invasive Surgical Procedures , Blood Loss, Surgical , Coronary Artery Bypass , Coronary Artery Disease/surgery , Humans , Treatment Outcome
19.
Angew Chem Int Ed Engl ; 60(12): 6553-6560, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33438257

ABSTRACT

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag2 Se on CoSe2 nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag2 Se-CoSe2 material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5 % anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag2 Se-CoSe2 interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces.

20.
J Am Chem Soc ; 142(13): 6400-6408, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-32176485

ABSTRACT

Selective and efficient catalytic conversion of carbon dioxide (CO2) into value-added fuels and feedstocks provides an ideal avenue to high-density renewable energy storage. An impediment to enabling deep CO2 reduction to oxygenates and hydrocarbons (e.g., C2+ compounds) is the difficulty of coupling carbon-carbon bonds efficiently. Copper in the +1 oxidation state has been thought to be active for catalyzing C2+ formation, whereas it is prone to being reduced to Cu0 at cathodic potentials. Here we report that catalysts with nanocavities can confine carbon intermediates formed in situ, which in turn covers the local catalyst surface and thereby stabilizes Cu+ species. Experimental measurements on multihollow cuprous oxide catalyst exhibit a C2+ Faradaic efficiency of 75.2 ± 2.7% at a C2+ partial current density of 267 ± 13 mA cm-2 and a large C2+-to-C1 ratio of ∼7.2. Operando Raman spectra, in conjunction with X-ray absorption studies, confirm that Cu+ species in the as-designed catalyst are well retained during CO2 reduction, which leads to the marked C2+ selectivity at a large conversion rate.

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