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1.
Bioact Mater ; 8: 381-395, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541408

RESUMO

This work was focused on study of anti-infection ability and its underlying mechanism of a novel dental implant made of titanium-copper (TiCu) alloy. In general, most studies on antibacterial implants have used a single pathogen to test their anti-infection ability using infectious animal models. However, dental implant-associated infections are polymicrobial diseases. We innovatively combine the classic ligature model in dogs with sucrose-rich diets to induce oral infections via the canine native oral bacteria. The anti-infection ability, biocompatibility and underlying mechanism of TiCu implant were systematically investigated in comparison with pure Ti implant via general inspection, hematology, imageology (micro-CT), microbiology (16S rDNA and metagenome), histology, and Cu ion detections. Compared with Ti implant, TiCu implant demonstrated remarkable anti-infection potentials with excellent biocompatibility. Additionally, the underlying anti-infection mechanism of TiCu implant was considered to involve maintaining the oral microbiota homeostasis. It was found that the carbohydrates in the plaques formed on the surface of TiCu implant were metabolized through the tricarboxylic acid cycle (TCA) cycles, which prevented the formation of an acidic microenvironment and inhibited the accumulation of acidogens and pathogens, thereby maintaining the microflora balance between aerobic and anaerobic bacteria.

2.
Food Chem ; 368: 130807, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411859

RESUMO

The combined use of selected Saccharomyces cerevisiae and non-Saccharomyces strains is becoming an effective way to achieve wine products with distinctive aromas. The purpose of this study was to further improve the wine aroma complexity through optimizing inoculation protocols of multi-starters. The three indigenous non-Saccharomyces strains (Torulaspora delbrueckii, Hanseniaspora vineae, and Lachancea thermotolerans) and their pairwise combinations (co-inoculation) were sequentially inoculated with S. cerevisiae in Petit Manseng grape must, respectively. Results evidenced a higher divergence in aroma compounds produced by two different non-Saccharomyces species compared to single species. Especially for the combination of T. delbrueckii and L. thermotolerans, the concentrations of most ethyl esters were further increased, contributing to a higher score of 'pineapple' note in agreement with sensory analysis. Our results highlighted that the inoculation of more than one non-Saccharomyces species is a potential strategy to improve the aroma diversity and quality of industrial wines.


Assuntos
Compostos Orgânicos Voláteis , Vinho , Fermentação , Hanseniaspora , Saccharomyces cerevisiae , Saccharomycetales , Compostos Orgânicos Voláteis/análise , Vinho/análise
3.
Oncol Rep ; 47(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34751411

RESUMO

The phosphatidylinositol­3­kinase catalytic subunit α (PIK3CA) gene is mutated in numerous human cancers. This mutation promotes the proliferation of tumor cells; however, the underlying mechanism is still not clear. In the present study, it was revealed that the PIK3CA mutation in colorectal cancer (CRC) HCT116 (MUT) rendered the cells more dependent on glutamine by regulating the glutamic­pyruvate transaminase 2 (GPT2). The dependence of glutamine increased the proliferation of cells in a normal environment and resistance to a suboptimal environment. Further study revealed that the mutated PIK3CA could regulate GPT2 expression not only through signal transduction molecule 3­phosphoinositide­dependent kinase (PDK1) but also through mitogen­activated protein kinase (MEK) molecules. In HCT116 cells, MEK inhibitor treatment could reduce the expression of GPT2 signaling molecules, thereby inhibiting the proliferation of CRC cells. A new signal transduction pathway, the PI3K/MEK/GPT2 pathway was identified. Based on these findings, MEK and PDK1 inhibitors were combined to inhibit the aforementioned pathway. It was revealed that the combined application of MEK and PDK1 inhibitors could promisingly inhibit the proliferation of MUT compared with the application of PI3K inhibitors, PDK1 inhibitors, or MEK inhibitors alone. In vivo, MEK inhibitors alone and combined inhibitors had stronger tumor­suppressing effects. There was no significant difference between the PDK1­inhibitor group and normal group in vivo. Thus, these results indicated that mutated PI3K affected GPT2 mediated by the MEK/PDK1 dual pathway, and that the PI3K/MEK/GPT2 pathway was more important in vivo. Inhibiting MEK and PDK1 concurrently could effectively inhibit the proliferation of CRC cells. Targeting the MEK and PDK1 signaling pathway may provide a novel strategy for the treatment of PIK3CA­mutated CRC.

4.
Talanta ; 237: 122896, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736712

RESUMO

Noroviruses are the leading cause of acute gastroenteritis and food-borne diseases worldwide. Thus, a rapid, accurate, and easy-to-implement detection method for controlling infection and monitoring progression is urgently needed. In this study, we constructed a novel sandwich-type electrochemical biosensor integrated with two specific recognition elements (aptamer and peptide) for human norovirus (HuNoV). The electrochemical biosensor was fabricated using magnetic covalent organic framework/pillararene heterosupramolecular nanocomposites (MB@Apt@WP5A@Au@COF@Fe3O4) as the signal probes. The sensor showed high accuracy and selectivity. The detection method does not need the extraction and amplification of virus nucleic acid and has a short turn-around time. Intriguingly, the proposed biosensor had a limit of detection of 0.84 copy mL-1 for HuNoV, which was the highest sensitivity among published assays. The proposed biosensor showed higher sensitivity and accuracy compared with immunochromatographic assay in the detection of 98 clinical specimens. The biosensor was capable of determining the predominant infection strain of GII.4 and also GII.3 and achieved 74% selectivity for HuNoV GII group. This study provides a potential method for point-of-care testing and highlights the integrated utilization of Apt and peptide in sensor construction.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Nanocompostos , Norovirus , Humanos , Imunoensaio
5.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34751416

RESUMO

Oxidative stress­induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element­binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2­induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2­induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

6.
Dev Comp Immunol ; 127: 104305, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34718077

RESUMO

Beetles are the most diverse group of insects in Insecta which can be found in almost every habitat and environment on Earth. The possessing of the rapid and effective immune defenses is one of the important factors for their success. It is generally recognized that beetles only rely on the non-specific innate immune defense, without immunological memory, to fight against pathogens. However, there was cumulative evidence for the innate immune memory in invertebrates, including beetles, over the last decades, implying that insect innate immunity is more complex and has more features than previously thought. In beetles, it has been well documented that the specific or nonspecific enhanced immunocompetence can persist throughout development within generations and can even be transferred to the descendents in the next generation. Although insect immune priming might be shaped by epigenetic modifications and transferring effectors, mRNA and microbial signals, the solid experimental evidence to support the causal relationship between any of them and immune priming is still scarce. The combined usage of 'omics' approaches and CRISPR/Cas9 in the appropriate insect models with well-known genetic background, Tribolium castaneum and Tenebrio molitor, will help us to decipher the molecular mechanisms by which immune priming occurs in beetles in depth.

7.
Neural Regen Res ; 17(3): 682-689, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380910

RESUMO

SNCA, GBA, and VPS35 are three common genes associated with Parkinson's disease. Previous studies have shown that these three genes may be associated with Alzheimer's disease (AD). However, it is unclear whether these genes increase the risk of AD in Chinese populations. In this study, we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA, SNCA, and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China. The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population. These findings suggest that the mutations in GBA, SNCA, and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University, China on March 9, 2016 (approval No. 201603198).

8.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(1): 159061, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610469

RESUMO

Trans fatty acids (TFA) in food can cause liver inflammation. Activation of NOD-like receptor protein-3 (NLRP3) inflammasome is a key factor in the regulation of inflammation. Accumulating evidence suggests that ERS-induced NLRP3 inflammasome activation underlies the pathological basis of various inflammatory diseases, but the precise mechanism has not been fully elucidated. Therefore, this paper focused on TFA, represented by elaidic acid (EA), to investigate the mechanism of liver inflammation. Levels of mRNA and protein were detected by RT-qPCR and Western blotting, the release of proinflammatory cytokines was measured by ELISA, and intracellular Ca2+ levels were determined by flow cytometer using Fluo 4-AM fluorescent probes. Our research indicated that EA induced the endoplasmic reticulum stress (ERS) response in Kupffer cells (KCs), accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which resulted in NLRP3 inflammasome formation, and eventually increased the release of inflammatory factors. NLRP3 inflammasome activation was inhibited when KCs were pretreated with ERS inhibitors (4-PBA) and MAPK selective inhibitors. Furthermore, when ERS was blocked, the MAPK pathway was inhibited.

9.
Sci Total Environ ; 806(Pt 4): 151484, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742807

RESUMO

Planetary boundaries define the safe operating space of human beings relative to the Earth's system, which is of great significance in helping human beings predict environmental safety limits. However, ecological boundaries have not been presented or downscaled to regional levels. Moreover, a method has not been developed to quantitatively measure the gap between the value of the services provided by the ecosystem and the size of the urban population and economy that the ecosystem can carry. Herein, we propose the concept and calculation model of the "ecological boundary" to quantitatively assess the ecosystem security gap size transgressed by humans. Ecological boundaries are defined as the maximum population and economic scale that a certain area can support under a certain ecologically productive area. The purpose of this paper is to investigate the ecological boundary in megacities, and Beijing is considered as a specific case. The results show that the consumption of natural resources has transgressed its ecological boundary in Beijing. The direct consequence is that the ecological well-being per capita continues to decrease. Fortunately, with decreases in the ecological footprint and land use/land cover change dynamic degree, the ecological boundary gap is gradually tightening. Moreover, the role of ecological boundaries as early warning signals of undesirable urban ecological environmental changes is discussed, the significance of the monetization of ecological boundaries is described, the factors underlying the ecological boundary gap in the process of accelerating urbanization in China are analyzed, and policy recommendations for resolving the threat to ecological security boundaries by megacities are presented. The primary purpose of our study is provide policymakers with information on the gap between the current well-being of humankind and critical capacity thresholds, which can help determine whether human activities have fallen into an unsustainable state that may result in undesirable eco-environmental changes that could have detrimental or even disastrous consequences for the population of a region.

10.
Sci Total Environ ; 806(Pt 1): 150537, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34844317

RESUMO

Effects of climate warming on trophic cascades are increasingly reported for large herbivores occupying northern latitudes. During the last 40 years, moose (Alces alces) in northeast China have lost nearly half of their historical distribution through their habitat shifting northwards. There are many possible causes of bottom-up and top-down effects of temperature and for moose in northeast China they are poorly understood. Of particular relevance are the effects of extrinsic environmental factors on gene flow, nutritional adaptions, and gut microbiota that occur as moose populations retreat northwards. We combined molecular biology, nutritional ecology and metagenomics to gain deeper mechanistic insights into the effects of temperature on moose populations. In this study, we revealed that the direction and intensity of gene flow is consistent with global warming driving retreats of moose populations. We interpret this as evidence for the northward movement of moose populations, with cooler northern populations receiving more immigrants and warmer southern populations supplying emigrants. Comparison across latitudes showed that warmer late spring temperatures were associated with plant community composition and facilitated related changes in moose protein and carbohydrate intake through altering forage availability, forage quality and diet composition. Furthermore, these nutrient shifts were accompanied by changes in gut microbial composition and functional pathways related to nutrient metabolism. This study provided insights into mechanisms driving effects of spatial heterogeneous warming on genetic, nutritional and physiological adaptions related to key demographic rates and patterns of survival of heat-sensitive ungulates along a latitude gradient. Understanding such changes helps to identify key habitat areas and plant species to ensure accurate assessment of population status and targeted management of moose populations.

11.
J Hazard Mater ; : 127865, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34848069

RESUMO

To cope with the current serious arsenate pollution problem, a new ternary layered double hydroxides (LDHs) containing Ni, Co and Mn with good performance was developed, guiding by DFT calculations. First, Ni, Co and Mn were screened as the metal sources to constitute the LDHs, due to their high ionic charge density. Then, Ni(II), Co(II) and Mn(III)-O octahedra were selected as the primary units for structuring the LDHs, because of their good chemical activity. Meanwhile, the ratio of metals in the ternary LDHs, favoring for arsenate removal, was optimized at 1:2:1. In addition, the synergistic effect among various metals in the LDHs was considered. The results suggested that in the case of single doping, all three metals can act as the center to promote chemical activity independently. On the contrary, when combined together, there is only one unilateral active center. Moreover, the existence of ligand covalent bonds between arsenate and LDHs was confirmed. Finally, a promising new NiCo2Mn-LDHs with the maximum adsorption capacity of 407.23 mg/g for arsenate removal had been prepared.

12.
Hortic Res ; 8(1): 262, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34848704

RESUMO

Water dropwort (Liyang Baiqin, Oenanthe javanica (BI.) DC.) is an aquatic perennial plant from the Apiaceae family with abundant protein, dietary fiber, vitamins, and minerals. It usually grows in wet soils and can even grow in water. Here, whole-genome sequencing of O. javanica via HiSeq 2000 sequencing technology was reported for the first time. The genome size was 1.28 Gb, including 42,270 genes, of which 93.92% could be functionally annotated. An online database of the whole-genome sequences of water dropwort, Water dropwortDB, was established to share the results and facilitate further research on O. javanica (database homepage: http://apiaceae.njau.edu.cn/waterdropwortdb ). Water dropwortDB offers whole-genome and transcriptome sequences and a Basic Local Alignment Search Tool. Comparative analysis with other species showed that the evolutionary relationship between O. javanica and Daucus carota was the closest. Twenty-five gene families of O. javanica were found to be expanded, and some genetic factors (such as genes and miRNAs) related to phenotypic and anatomic differentiation in O. javanica under different water conditions were further investigated. Two miRNA and target gene pairs (miR408 and Oja15472, miR171 and Oja47040) were remarkably regulated by water stress. The obtained reference genome of O. javanica provides important information for future work, thus making in-depth genetic breeding and gene editing possible. The present study also provides a foundation for the understanding of the O. javanica response to water stress, including morphological, anatomical, and genetic differentiation.

13.
Anal Chem ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851092

RESUMO

The K+ and Na+ levels in cells have a synergistic effect on many biological processes (BPs); therefore, the simultaneous detection of them is important. Here, we propose a novel Y-shaped DNA sensor for simultaneous monitoring of Na+ and K+ in extracellular microenvironments. The designed sensor contributed to the selective response to the above two ions. In addition, it performed the imaging of the above two ions on the cell surface in a real-time, on-site manner, which would shed more light on the association of the Na+/K+ content with regulatory BPs. We believe that this new strategy will be a promising tool to investigate the synergy of Na+/K+ in regulating different BPs.

14.
Pediatrics ; 148(6)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851411

RESUMO

BACKGROUND: Acute otitis media (AOM) is the most frequent reason for children to be prescribed antimicrobial treatment. Surfactants are naturally occurring substances that may restore the eustachian tube's function and potentially enhance resolution of AOM. METHODS: This was a phase 2a, single-center, double-blind, randomized, placebo-controlled, parallel group clinical trial to assess safety, tolerability, and efficacy of 20 mg per day intranasal OP0201 as an adjunct therapy to oral antimicrobial agents for treating AOM in young children. We randomly assigned 103 children aged 6 to 24 months with AOM to receive either OP0201 or placebo twice daily for 10 days. All children received amoxicillin-clavulanate 90/6.4 mg/kg per day in 2 divided doses for 10 days. Participants were managed for up to 1 month. Postrandomization visits occurred between days 4 and 6 (visit 2), days 12 and 14 (visit 3), and days 26 and 30 (visit 4). Primary efficacy endpoints were resolution of a bulging tympanic membrane at visit 2 and resolution of middle-ear effusion at visit 3. RESULTS: No clinically meaningful differences between treatment groups were apparent for primary or secondary endpoints. There were no safety concerns identified. CONCLUSIONS: In young children with AOM, intranasally administered surfactant (OP0201) did not improve clinical outcomes. Further research may be warranted among children with persistent middle-ear effusion.

15.
Scand J Psychol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34734420

RESUMO

Moral identity and empathy are two important contributors of charitable donation. But there are also inconsistent findings which suggest the existence of moderating variables. This research investigated their effects on charitable donation when the fictional recipients have or have not responsibility for HIV infection. Through four between-subjects experiments, we respectively explored the effect of responsibility of AIDS patients (blameless vs. blameful; manipulated by different ways of HIV infection) on donation, and its interaction with trait moral identity (study 1a, n = 313, Mage = 19.37, 70% females), primed moral identity (study 1b, n = 392, Mage = 19.43, 72% females), trait empathy (study 2a, n = 310, Mage = 19.34, 67% females), and primed empathy (study 2b, n = 366, Mage = 19.39, 55% females). Measures of moral identity and empathy, and a priming technique with moral identity and empathy words as stimuli were used research tools. The results demonstrated that when AIDS patients were not responsible for their plight (blameless), moral identity and empathy (regardless of trait or activated) showed positive effects on donation. When AIDS patients were responsible for their plight (blameful), however, all positive effects disappeared. Trait moral identity even showed a negative effect on donation. These results indicated that the prosocial effects of moral identity and empathy are conditioned by characteristics of the beneficiaries.

16.
Chemosphere ; : 132766, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34740703

RESUMO

Numerous attempts have been utilized to unveil the occurrences of antibiotic resistance genes (ARGs) in human-associated and non-human-associated samples. However, spoiled household chemicals, which are usually neglected by the public, may be also a reservoir of ARGs because of the excessive and inappropriate uses of industrial drugs. Based upon the Comprehensive Antibiotic Research Database, a metagenomic sequencing method was utilized to detect and quantify Antibiotic Resistance Ontology (AROs) in six spoiled household chemicals, including hair conditioner, dishwashing detergent, bath shampoo, hand sanitizer, and laundry detergent. Proteobacteria was found to be the dominant phylum in all the samples. Functional annotation of the unigenes obtained against the KEGG pathway, eggNOG and CAZy databases demonstrated a diversity of their functions. Moreover, 186 types of AROs that were members of 72 drug classes were identified. Multidrug resistance genes were the most dominant types, and there were 17 AROs whose resistance mechanisms were categorized into the resistance-nodulation-cell division antibiotic efflux pump among the top 20 AROs. Moreover, Proteobacteria was the dominant carrier of AROs with the primary resistance mechanism of antibiotic efflux. The maximum temperature of the months of collection significantly affected the distributions of AROs. Additionally, the isolated individual bacterium from spoiled household chemicals and artificial mixed communities of isolated bacteria demonstrated diverse resistant abilities to different biocides. This study demonstrated that there are abundant microorganisms and a broad spectrum profile of AROs in spoiled household chemicals that might induce a severe threat to public healthy securities and merit particular attention.

17.
Magn Reson Med ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34752642

RESUMO

PURPOSE: To identify a reliable metric for predicting the encoding capability of CEST MR fingerprinting acquisition schedules for pH quantification, which may facilitate CEST MR fingerprinting protocol optimization. METHODS: Numerical simulations and Cr phantom MRI experiments were conducted at 3 Tesla under representative CEST MR fingerprinting sampling scenarios, including the pseudorandomization of imaging parameters (e.g., saturation power B1 , saturation frequency offset, saturation time, and relaxation time), and variation of the maximum saturation power B1max , B1 number, and sampling pattern. The CEST effect at 2 ppm was measured using asymmetry analysis and matched to a predefined dictionary to determine the pH. The pH quantification error was assessed using RMSE. Three metrics, namely the Cramer-Rao bound, dot product, and Euclidean distance, were calculated for each sampling scenario, and their relationships with the pH RMSE were investigated to examine their effectiveness for predicting the encoding capability of sampling schedules for pH quantification. RESULTS: Both simulation and phantom studies revealed that the Cramer-Rao bound metric consistently exhibited superior performance for predicting the pH quantification error. Although dot product exhibited good encoding capability prediction in most sampling scenarios, it failed in the scenario with varied B1 numbers. In contrast, Euclidean distance exhibited the worst performance among the 3 metrics in all scenarios. CONCLUSION: Superior over dot product and Euclidean distance, the Cramer-Rao bound metric may reliably predicting the encoding capability of CEST MR fingerprinting sampling strategies and may be useful for guiding CEST MRI protocol optimization.

18.
Soft Matter ; 17(43): 9871-9875, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34724526

RESUMO

An artificial light-harvesting system with two-step sequential energy transfer was constructed in aqueous media based on cyano-substituted p-phenylenevinylene derivative (PPTA) and bis-(p-sulfonatocalix[4]arenes) (BSC4) supramolecular polymers formed through host-guest interactions, in which two different fluorescent dyes, eosin Y (EY) and sulforhodamine (SR101), were employed as energy acceptors. The obtained artificial light-harvesting system can achieve an efficient two-step energy transfer process from PPTA-BSC4 to EY and then to SR101 with high energy-transfer efficiencies of up to 36.6% and 40.8%, respectively. More importantly, the harvested energy from the PPTA-BSC4 + EY + SR101 system can be used to promote the dehalogenation of α-bromoacetophenone with a yield of 89% in aqueous solution.

19.
Chemphyschem ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729887

RESUMO

The coordination atoms of metal active site in transition metal N-doped carbon single atom electrocatalysts play a vital role in dominating the catalytic performance of oxygen reduction reaction (ORR) at the cathode of fuel cells or metal-air cells. In view of weak adsorption ability of Ni active site in NiN4 -C catalysts to oxygen intermediate states, herein we introduce boron atoms with smaller electronegativity than N and C atoms to modulate the local coordination environment and electronic structures of Ni site. First-principles density functional calculations reveal that both B substitution for N atoms (NiN2 B2 -C) and B coordinating with N and C (NiN4 B8 -C) can effectively optimize the Gibbs free energy of oxygen intermediate states and hence improve the catalytic activity of the materials. In addition, we propose that the trend change in catalytic activity is mainly governed by the filling of antibonding orbitals between Ni-3d and O-2p states near the Fermi level.

20.
Mol Ther Nucleic Acids ; 26: 879-891, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760335

RESUMO

RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases.

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