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Prussian white (PW) is one of the most promising candidates as a cathode for sodium-ion batteries (SIBs) because of its high theoretical capacity, excellent rate performance, and low production cost. However, PW materials suffer severe capacity decay during long-term cycling. In this work, a robust cathode electrolyte interface (CEI) is designed on the PW cathode by employing cresyl diphenyl phosphate (CDP) and adiponitrile (ADN) as electrolyte additives. CDP and ADN possess higher highest occupied molecular orbital energy levels (HOMO) than other solvents, leading to the preferential decomposition of CDP and ADN to construct an inorganics-rich CEI layer in situ on the PW cathode. Benefiting from this CEI layer, the degradation of PW is effectively inhibited during the long cycling. The Na||PW cell achieves an excellent cycling performance with a capacity retention of 85.62% after 1400 cycles. This work presented here provides a feasible strategy for improving the cycling performance of PW by electrolyte modification.
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The development of thermally stable separators is a promising approach to address the safety issues of lithium-ion batteries (LIBs) owing to the serious shrinkage of commercial polyolefin separators at elevated temperatures. However, achieving controlled nanopores with a uniform size distribution in thermostable polymeric separators and high electrochemical performance is still a great challenge. In this study, nanoporous polyimide (PI) membranes with excellent thermal stability as high-safety separators is developed for LIBs using a superspreading strategy. The superspreading of polyamic acid solutions enables the generation of thin and uniform liquid layers, facilitating the formation of thin PI membranes with controllable and uniform nanopores with narrow size distribution ranging from 121 ± 5 nm to 86 ± 6 nm. Such nanoporous PI membranes display excellent structural stability at elevated temperatures up to 300 °C for at least 1 h. LIBs assembled with nanoporous PI membranes as separators show high specific capacity and Coulombic efficiency and can work normally after transient treatment at a high temperature (150 °C for 20 min) and high ambient temperature, indicating their promising application as high-safety separators for rechargeable batteries.
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AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.
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Delta like non-canonical Notch ligand 1 (DLK1), as a member of epidermal growth factor-like family, plays a critical role in somatic growth, tissue development and possibly tissue renewal. Though previous studies had indicated that DLK1 contributed to adipogenesis and myogenesis, it's still controversial whether DLK1 affects angiogenesis and how it interacts with Notch signaling with numerous conflicting reports from different models. Based on our preliminary finding that DLK1 expression was up-regulated in mice ischemic gastrocnemius and in the border zone of infarcted myocardium, we administered either recombinant DLK1 (rDLK1) or PBS in C57BL/6 mice after establishment of hindlimb ischemia (HLI) and myocardial infarction (MI), respectively. Exogenous rDLK1 administration significantly improved both blood perfusion of mice ischemic hindlimbs and muscle motor function on the 3rd, 7th day after HLI, by promoting neovascularization. Similar effect on neovascularization was verified in mice on the 28th day after MI as well as improvement of cardiac failure. Correspondingly, the number of CD34+KDR+ cells, indicated as endothelial progenitor cells (EPCs), was significantly in mice ischemic gastrocnemius by rDLK1 administration, which was abrogated by DAPT as the specific inhibitor of Notch intracellular domain (NICD). Furthermore, bone marrow mononuclear cells were obtained from C57BL/6 mice and differentiated to EPCs ex vivo. Incubation with rDLK1 triggered Notch1 mRNA and NICD protein expressions in EPCs as exposed to hypoxia and serum deprivation, promoting EPCs proliferation, migration, anti-apoptosis and tube formation. Otherwise, rDLK1 incubation significantly decreased intracellular and mitochondrial reactive oxygen species, increased ATP content and mitochondrial membrane potential, downregulated short isoform of OPA-1 expression whereas upregulated mitofusin (-1, -2) expression in EPCs by Notch1 signaling, which were all abrogated by DAPT. In summary, the present study unveils the pro-angiogenesis and its mechanism of rDLK1 through activation of Notch1 signaling in endothelial progenitor cells.
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INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.
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Hipertensão Pulmonar , Mediastinite , Hipertensão Arterial Pulmonar , Esclerose , Masculino , Humanos , Pessoa de Meia-Idade , Mediastino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Mediastinite/complicações , Mediastinite/diagnóstico , Hipertensão Arterial Pulmonar/patologiaRESUMO
In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310â mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.
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BACKGROUND: TAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value. METHODS: CIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference. RESULTS: There was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis. CONCLUSIONS: This study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.
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Biomarcadores Tumorais , MicroRNAs , Humanos , Biomarcadores Tumorais/genética , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genéticaRESUMO
A novel nanocomposite material, ferric vanadate intertwined multi-walled carbon nanotubes (FeV/MWCNTs), has been designed which was drop-coated onto a glassy carbon electrode (GCE). The constructed sensor was used for the sensitive determination of uric acid (UA) in fetal bovine serum (FBS) and human serum (HS). A series of characterization and electrochemical tests showed that the ultrasound-assisted assembly of FeV with MWCNTs not only overcame the disadvantages of low conductivity and easy (unwanted) aggregation, but also avoided the decrease in effective surface area due to the severe aggregation of each individual raw material. The fabricated FeV/MWCNTs nanocomposites exhibited higher conductivity, larger effective surface area, and better electrocatalytic activity. In addition, under optimized conditions, the developed electrochemical sensor FeV/MWCNTs/GCE has a lower limit of detection (LOD, 0.05 µM; Ep = 0.268 V vs. Ag/AgCl) and wider linear range (0.20-100 µM), which can satisfy the criteria of trace UA detection. The results of UA determination in FBS (recovery = 95.5-103%; RSD ≤ 3.1%) and HS (recovery = 95.5-103%; RSD ≤ 4.3%) further validated the feasibility of FeV/MWCNTs-based electrochemical sensors for the determination of UA in biological fluids.
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Nanocompostos , Nanotubos de Carbono , Humanos , Nanotubos de Carbono/química , Soroalbumina Bovina , Ácido Úrico , Vanadatos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Nanocompostos/química , FerroRESUMO
Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.
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Dinoprosta , Oftalmopatia de Graves , Humanos , Dinoprosta/metabolismo , Adipogenia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Oftalmopatia de Graves/patologia , Fibroblastos/metabolismo , Células CultivadasRESUMO
Cyclic ether, such as 1,3-dioxolane (DOL), are promising solvent for low-temperature electrolytes because of the low freezing point. Their use in electrolytes, however, is severely limited since it easily polymerizes in the presence of lithium inorganic salts. The trace water plays a key role via providing the source (proton) for chain initiation, which has, unfortunately, been neglected in most cases. In this work, we present an electrophile, trimethylsilyl isocyanate (Si-NCO), as the water scavenger, which eliminates moisture by a nucleophilic addition reaction. Si-NCO allows DOL to maintain liquid over a wide temperature range even in high-concentration electrolyte. Electrolyte with Si-NCO additive shows promising low-temperature performance. Our finding expands the use of cyclic ether solvents in the presence of inorganic salts and highlights a large space for unexplored design of water scavenger with electrophilic feature for low-temperature electrolytes.
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Biological ion channels penetrated through cell membrane form unique transport pathways for selective ionic conductance. Replicating the success of ion selectivity with mixed matrix membranes (MMMs) will enable new separation technologies but remains challenging. Herein, we report a soft substrate-assisted solution casting method to develop MMMs with penetrating subnanochannels for selective metal ion conduction. The MMMs are composed of penetrating Prussian white (PW) microcubes with subnanochannels in dense polyimide (PI) matrices, achieving selective monovalent metal ion conduction. The ion selectivity of K+ /Mg2+ is up to 14.0, and the ion conductance of K+ can reach 45.5â µS with the testing diameter of 5â mm, which can be further improved by increasing the testing area. Given the diversity of nanoporous materials and polymer matrices, we expect that the MMMs with penetrating subnanochannels could be developed into a versatile nanofluidic platform for various emerging applications.
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Metais , Nanoporos , Membrana Celular , Íons , PolímerosRESUMO
Metal/nitrogen-doped carbons (M-N-C) are promising candidates as oxygen electrocatalysts due to their low cost, tunable catalytic activity and selectivity, and well-dispersed morphologies. To improve the electrocatalytic performance of such systems, it is critical to gain a detailed understanding of their structure and properties through advanced characterization. In situ X-ray absorption spectroscopy (XAS) serves as a powerful tool to probe both the active sites and structural evolution of catalytic materials under reaction conditions. In this review, we firstly provide an overview of the fundamental concepts of XAS and then comprehensively review the setup and application of in situ XAS, introducing electrochemical XAS cells, experimental methods, as well as primary functions on catalytic applications. The active sites and the structural evolution of M-N-C catalysts caused by the interplay with electric fields, electrolytes and reactants/intermediates during the oxygen evolution reaction and the oxygen reduction reaction are subsequently discussed in detail. Finally, major challenges and future opportunities in this exciting field are highlighted.
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KVPO4 F is one of the most competitive cathode candidates for potassium-ion batteries (KIBs) because of its high output voltage and energy density. Although the gravimetric energy density of KIBs is intensively discussed in literature, little attention is paid to the volumetric energy density. In view of this, pomegranate-like carbon-coated KVPO4 F microspheres with a high volumetric energy density are designed in this work. The nano-sized primary particles with carbon sheets in KVPO4 F microspheres enable promis rate capability by enhancing the K+ diffusion kinetics, while the micro-sized spheres guarantee the improvement of cycling stability. Owing to the dense hierarchical microspheres, the volumetric energy density of cells is greatly improved compared to bulk materials. This cathode delivers a reversible capacity of 101.5 mA h g-1 at 0.3 C with an average output voltage of 4.0 V and a capacity retention of 85.1% after 200 cycles. The KVPO4 F@C microspheres have a compact density of 2.45 g cm-3 and further offer a high volumetric energy density up to 891.3 Wh L-1 . The overcharge behavior of KVPO4 F in the first three cycles is also revealed. The presented KVPO4 F@C microspheres cathode provides a new sight for developing KIBs with large volumetric energy density.
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A base-promoted [4 + 2] annulation of pyrrole-2-carbaldehyde derivatives with ß,γ-unsaturated α-ketoesters for the syntheses of multisubstituted 5,6-dihydroindolizines was developed. Using DBN as a base, the reaction proceeds smoothly under mild conditions to provide the target products in moderate to high yields, and many useful functional groups can be tolerated.
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Ésteres , Pirróis , Catálise , CiclizaçãoRESUMO
PURPOSE: To describe the genetic and clinical features of nineteen patients from eleven unrelated Chinese pedigrees with OPA1-related autosomal dominant optic atrophy (ADOA) and define the phenotype-genotype correlations. METHODS: Detailed ophthalmic examinations were performed. Targeted next-generation sequencing (NGS) was conducted in the eleven probands using a custom designed panel PS400. Sanger sequencing and cosegregation were used to verify the identified variants. The pathogenicity of gene variants was evaluated according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Nineteen patients from the eleven unrelated Chinese ADOA pedigrees had impaired vision and optic disc pallor. Optical coherence tomography showed significant thinning of the retinal nerve fiber layer. The visual field showed varying degrees of central or paracentral scotoma. The onset of symptoms occurred between 3 and 24 years of age (median age 6 years). Eleven variants in OPA1 were identified in the cohort, and nine novel variants were identified. Among the novel variants, two splicing variants c.984 + 1_984 + 2delGT, c.1194 + 2 T > C, two stop-gain variants c.1937C > G, c.2830G > T, and one frameshift variant c.2787_2794del8, were determined to be pathogenic based on ACMG. A novel splicing variant c.1316-10 T > G was determined to be likely pathogenic. In addition, a novel missense c.1283A > C (p.N428T) and two novel splicing variants c.2496G > A and c.1065 + 5G > C were of uncertain significance. CONCLUSIONS: Six novel pathogenic variants were identified. The findings will facilitate genetic counselling by expanding the pathogenic mutation spectrum of OPA1.
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Atrofia Óptica Autossômica Dominante , GTP Fosfo-Hidrolases/genética , Estudos de Associação Genética , Humanos , Mutação , Atrofia Óptica Autossômica Dominante/genética , Atrofia Óptica Autossômica Dominante/patologia , LinhagemRESUMO
Cadmium (Cd) is one of the toxic heavy metals found widely in the environment. Skin is an important target organ of Cd exposure. However, the adverse effects of Cd on human skin are still not well known. In this study, normal human skin keratinocytes (HaCaT cells) were studied for changes in cell viability, morphology, DNA damage, cycle, apoptosis, and the expression of endoplasmic reticulum (ER) stress-related genes (XBP-1, BiP, ATF-4, and CHOP) after exposure to Cd for 24 h. We found that Cd decreased cell viability in a concentration-dependent manner, with a median lethal concentration (LC50) of 11 µM. DNA damage induction was evidenced by upregulation of the level of γ-H2AX. Furthermore, Cd induced G0/G1 phase cell cycle arrest and apoptosis in a dose-dependent manner and upregulated the mRNA levels of ER stress biomarker genes (XBP-1, BiP, ATF4, and CHOP). Taken together, our results showed that Cd induced cytotoxicity and DNA damage in HaCaT cells, eventually resulting in cell cycle arrest in the G0/G1 phase and apoptosis. In addition, ER stress may be involved in Cd-induced HaCaT apoptosis. Our data imply the importance of reducing Cd pollution in the environment to reduce its adverse impacts on human skin.
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Cádmio , Estresse do Retículo Endoplasmático , Apoptose , Cádmio/toxicidade , Humanos , Queratinócitos , RNA MensageiroRESUMO
Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin. In this study, we first evaluated the detrimental effects and tried to uncover the underlying mechanisms of TCPP on human skin keratinocytes (HaCaT) after 24 h exposure. We found that TCPP caused a concentration-dependent decrease in HaCaT cell viability after exposure to 1.56-400 µg/mL for 24 h, with an IC50 of 275 µg/mL. TCPP also promoted the generation of intracellular reactive oxygen species (ROS) and triggered DNA damage, evidenced by an increase of phosphorylated histone H2A.X (γH2A.X) in the nucleus. Furthermore, the cell cycle was arrested at the G1 phase at 100 µg/mL by upregulation of the mRNA expression of p53 and p21 and downregulation of cyclin D1 and CDK4 expression. Additionally, both the senescence-associated-ß-galactosidase activity and related proinflammatory cytokine IL-1ß and IL-6 were elevated, indicating that TCPP exposure caused cellular senescence may be through the p53-dependent DNA damage signal pathway in HaCaT cells. Taken together, our data suggest that flame-retardant exposure may be a key precipitating factor for human skin aging.
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Retardadores de Chama , Envelhecimento da Pele , Humanos , Senescência Celular , Retardadores de Chama/toxicidade , Queratinócitos/metabolismo , Compostos Organofosforados/toxicidade , Compostos Organofosforados/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
A bacterial strain designated KDG-16 T is isolated from a freshwater waterfall in Taiwan and characterized to determine its taxonomic affiliation. Cells of strain KDG-16 T are Gram-stain-negative, strictly aerobic, motile by gliding, rod-shaped and form light yellow colonies. Optimal growth occurs at 20-25 °C, pH 6-7, and with 0% NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set reveal that strain KDG-16 T is affiliated with species in the genus Flavobacterium. Analysis of 16S rRNA gene sequences shows that strain KDG-16 T shares the highest similarity with Flavobacterium terrigena DSM 17934 T (97.7%). The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between strain KDG-16 T and the closely related Flavobacterium species are below the cut-off values of 95-96, 90 and 70%, respectively, used for species demarcation. Strain KDG-16 T contains iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH as the predominant fatty acids. The polar lipid profile consists of phosphatidylethanolamine, one uncharacterized aminophospholipid, one uncharacterized phospholipid, two uncharacterized aminolipids and two uncharacterized lipids. The major polyamine is homospermidine. The major isoprenoid quinone is MK-6. Genomic DNA G + C content of strain KDG-16 T is 31.6%. Based on the polyphasic taxonomic data obtained, strain KDG-16 T is considered to represent a novel species in the genus Flavobacterium, for which the name Flavobacterium difficile sp. nov. is proposed. The type strain is KDG-16 T (= BCRC 81194 T = LMG 31332 T).
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Flavobacterium , Água Doce , Ácidos Graxos , Flavobacterium/classificação , Flavobacterium/genética , Água Doce/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Especificidade da Espécie , TaiwanRESUMO
Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
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Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Tranilcipromina/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tranilcipromina/análogos & derivados , Tranilcipromina/químicaRESUMO
One mononuclear complex [Dy(Htpy)(NO3)2(acac)] (1) and a tpy--extended 1D chain {[Dy(CH3OH)(NO3)2(tpy)]·CH3OH}n (2) (Htpy = 4'-(4-hydroxyphenyl)-2,2':6',2''-terpyridine, Hacac = acetylacetone) were successfully designed to investigate the effect of bond length tuning around the DyIII cation on the magnetic dynamics of single-molecule magnets (SMMs). Interestingly, two magnetic entities possess the same local coordination sphere (N3O6-donor) as well as the configuration (Muffin, Cs) of dysprosium centers. Only a slight difference in structure results from purposefully substituting the acetylacetone ligand in 1 with hydroxyl oxygen from tpy- linkage and one methanol molecule in 2. However, the remarkable differences in dynamics behavior were clearly found between them. Compound 1 possesses a thermal-activated effective energy barrier (Ueff/kB) of 22.7 K under a 0 kOe direct current (dc) field and negligible hysteresis loop at 2.0 K, while complex 2 shows high-performance SMM behavior with the largest energy barrier of 354.36 K among the reported nine-coordinated DyIII-based systems and the magnetic hysteresis up to 4.0 K at a sweep rate of 200 Oe s-1. These experimental results combined with the previous reported data reveal that the shortest bond and the bond length difference around the DyIII center synergistically determine the dynamics of SMMs. The uniaxial anisotropy increases with the decrease of the shortest bond and the increase of the bond length difference, which is confirmed by the theoretical calculations.