Anion doping is one of the most widely adopted strategies to improve the electrochemical performance of cathode materials for Li-ion batteries. However, undesirable side effects are often observed ...together with enhanced electrochemical properties, leading to an unsatisfactory overall performance. In order to develop an anion doping strategy which enhances the positive effects and suppresses undesirable side effects, the understanding of their origin at the atomic scale is a crucial step. In this work, using density functional theory (DFT), we report a systematic study on the effects of three common anion dopants (F, S, Cl) on a wide range of properties of a model cathode material, LiNiO2, including redox potential, ionic conductivity, Li/Ni exchange, lattice distortion, and Ni migration upon delithiation. The results show that the dopants improve certain properties but worsen others, revealing some distance-dependent features. Overall, our work shows conflicting roles of anion doping on the battery voltage, rate performance, and structural stability of the cathode material. By identifying the origins of the different roles, we propose a rational anion doping strategy for the optimization of the overall electrochemical performance of the cathode material. These results for LiNiO2 can also promote anion doping studies and improved materials design in other Ni-rich layered oxide cathode materials.
The Zr solvent solution method, which allows primary and secondary particles of LiNi
0.90
Co
0.05
Mn
0.05
O
2
(NCM) to be uniformly doped with Zr and simultaneously to be coated with an Li
2
ZrO
3
...layer, is introduced in this paper. For Zr doped NCM, which is formed using the Zr solvent solution method (L-NCM), most of the pinholes inside the precursor disappear owing to the diffusion of the Zr dopant solution compared with Zr-doped NCM, which is formed using the dry solid mixing method from the (Ni
0.90
Co
0.05
Mn
0.05
)(OH)
2
precursor and the Zr source (S-NCM), and Li
2
ZrO
3
is formed at the pinhole sites. The mechanical strength of the powder is enhanced by the removal of the pinholes by the formation of Li
2
ZrO
3
resulting from diffusion of the solvent during the mixing process, which provides protection from cracking. The coating layer functions as a protective layer during the washing process for removing the residual Li. The electrochemical performance is improved by the synergetic effects of suitable coatings and the enhanced structural stability. The capacity-retentions for 2032 coin cells are 86.08%, 92.12%, and 96.85% at the 50
th
cycle for pristine NCM, S-NCM, and L-NCM, respectively. The superiority of the liquid mixing method is demonstrated for 18 650 full cells. In the 300
th
cycle in the voltage range of 2.8-4.35 V, the capacity-retentions for S-NCM and L-NCM are 77.72% and 81.95%, respectively.
The Zr solvent solution method, which allows primary and secondary particles of LiNi
0.90
Co
0.05
Mn
0.05
O
2
(NCM) to be uniformly doped with Zr and simultaneously to be coated with an Li
2
ZrO
3
layer, is introduced in this paper.
Alpha‐2‐Glycoprotein 1, Zinc‐binding (AZGP1, ZAG) is a secreted protein that is synthesized by adipocytes and epithelial cells; it is downregulated in several malignancies such as breast, prostate, ...liver and lung cancers. However, its function remains unclear in cholangiocarcinoma (CCA). Here, we evaluated the impact AZGP1 in CCA using Gene Expression Omnibus (GEO) and GEPIA. In addition, we analysed AZGP1 expression using quantitative reverse transcription PCR and western blotting. Expression of AZGP1 was nearly deficient in CCA patients and cell lines and was associated with poor prognosis. AZGP1 overexpression upregulated apoptosis markers. Co‐immunoprecipitation experiments showed that AZGP1 interacts with tripartite motif‐containing protein 25 (TRIM25), and tissue microarray and bioinformatic analysis showed that AZGP1 is negatively correlated with TRIM25 expression in CCA. Thereafter, TRIM25 knockdown led to AZGP1 upregulation and induced cancer cell apoptosis. TRIM25 targets AZGP1 for degradation by catalysing its ubiquitination. AZGP1 overexpression significantly suppressed tumour growth in a xenograft mouse model. This study findings suggest that AZGP1 is a potential therapeutic target or a diagnostic biomarker for treating patients with CCA.
The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and ...Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36 915 patients with ARIs, and viral nucleic acids were detected by real‐time (reverse‐transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV). The overall positive rate of patient specimens was 49.4% (18 236/36 915), 5% of which carried two or more viruses simultaneously. HRV (15.6%) was the most predominantly detected virus, followed by IFVs (14.6%), HAdV (7.5%), HPIVs (5.8%), HCoVs (4.2%), HRSVs (3.6%), HBoV (1.9%), and HMPV (1.6%). Most of the ARIs were significantly correlated with clinical symptoms of fever, cough, and runny nose. Although HRV and HAdV were frequently detected throughout the year in patients, other respiratory viruses showed apparent seasonality. HRSVs and IFVs were the major causative agents of acute respiratory diseases in infants and young children. Overall, this study demonstrates a meaningful relationship between viral infection and typical manifestations of known clinical features as well as seasonality, age distribution, and co‐infection among respiratory viruses. Therefore, these data could provide useful information for public health management and to enhance patient care for primary clinicians.
Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted ...tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (
p
< 0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various proteins and microRNAs (miRNAs) associated with neurogenesis and/or angiogenesis compared to fibro-EVs. We further analyzed those miRNAs and found that miRNA-184 and miRNA-210 were essential for promoting neurogenesis and angiogenesis of MSC-EVs, respectively. MSC-EVs represent an ideal alternative to MSCs for stroke treatment, with similar medicinal capacity but an improved safety profile that overcomes cell-associated limitations in stem cell therapy.
Although histone deacetylase inhibitors (HDACi) alone could be clinically useful, these are most recently used in combination with other anticancer agents in clinical trials for cancer treatment. ...Recently, we reported the anticancer activity of an HDAC6‐selective inhibitor A452 toward various cancer cell types. This study aims to present a potent synergistic antiproliferative effect of A452/anticancer agent treatment in colorectal cancer cells (CRC) cells, independently of the p53 status. A452 in combination with irinotecan, or SAHA is more potent than either drug alone in the apoptotic pathway as evidenced by activated caspase‐3 and PARP, increased Bak and pp38, decreased Bcl‐xL, pERK, and pAKT, and induced apoptotic cells. Furthermore, A452 enhances DNA damage induced by anticancer agents as indicated by the increased accumulation of γH2AX and the activation of the checkpoint kinase Chk2. The silencing of HDAC6 enhances the cell growth inhibition and cell death caused by anticancer agents. In addition, A452 induces the synergistic suppression of cell migration and invasion. This study suggests a mechanism by which HDAC6‐selective inhibition can enhance the efficacy of specific anticancer agents in CRC cells.
Stem cell-based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell-based therapy in patients ...with ischemic stroke.
In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging.
For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference.
Stem cell-based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01716481.
Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation ...failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet. Here we show that several signaling pathways as well as many genes and microRNAs are dysregulated in the endometrium of patients with RIF (RIFE). Whereas unsupervised hierarchical clustering showed that overall mRNA and microRNA profiles of RIFE were similar to those of endometria of healthy women, many genes were significantly dysregulated in RIFE (cut off at 1.5 fold change). The majority (~75%) of differentially expressed genes in RIFE including S100 calcium binding protein P (S100P), Chemokine (C-X-C motif) ligand 13 (CXCL13) and SIX homeobox 1 (SIX1) were down-regulated, suggesting that reduced uterine expression of these genes is associated with RIF. Gene Set Enrichment analyses (GSEA) for mRNA microarrays revealed that various signaling pathways including Leukemia inhibitory factor (LIF) signaling and a P4 response were dysregulated in RIFE although expression levels of Estrogen receptor α (ERα) and Progesterone receptor (PR) were not significantly altered in RIFE. Furthermore, expression and phosphorylation of Signal transducer and activator of transcription 3 (STAT3) are reduced and a gene set associated with Janus kinase (JAK)-STAT signaling pathway is systemically down-regulated in these patients. Pairwise analyses of microRNA arrays with prediction of dysregulated microRNAs based on mRNA expression datasets demonstrated that 6 microRNAs are aberrantly regulated in RIFE. Collectively, we here suggest that dysregulation of several major signaling pathways and genes critical for uterine biology and embryo implantation may lead to uterine abnormalities in patients with RIF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no ...pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)–induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.
Reversible formate (HCOO–) dehydrogenation and bicarbonate (HCO3 –) hydrogenation would be desirable for the utilization and storage of hydrogen (H2) as an effective energy carrier. Carbon-supported ...Pd-based nanoparticles demonstrated enormous competitive advantages for these reactions. However, the fundamental mechanisms underlying these reversible reactions have not yet been elucidated. Herein, we report the reaction pathways for reversible reactions on a Pd-based catalyst using density functional theory (DFT) calculations and propose key factors for improving the reaction efficiency. As the first essential step, the difficulty in the conventional DFT modeling, that is simulation of an anion environment caused by HCOO–, was overcome by designing two-sided Pd12 nanoclusters supported on graphene (Pd12NC-G) with extra electrons. Using Pd12NC-G, we demonstrated that the key factor determining the potential limiting steps for the reversible reaction was desorption of hydrogen in HCOO– dehydrogenation (1.24 eV) and HCO3 – hydrogenation (1.49 eV). The key factor was the same in Pd12NC-N1G, Pd12NC-N2G, and Pd12NC-N3G (where N1, N2, and N3 represent the number of N atoms doped on carbon). Among these, the Pd12NC-N2G model with the appropriate amount of nitrogen doping showed optimal hydrogen adsorption strength corresponding to the smallest d-band center and spin density values, resulting in the lowest energy barriers for HCOO– dehydrogenation (0.76 eV) and HCO3 – hydrogenation (0.96 eV). Based on harmonization between electronic and geometrical properties, we demonstrated that the appropriate level of nitrogen doping can provide the optimal balance between the magnitude of reactivity and the number of sites for improving the efficiency of the reversible reactions.
PDF
