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1.
Artigo em Inglês | MEDLINE | ID: mdl-33825459

RESUMO

Li-rich cathode materials possess a much higher theoretical energy density than all intercalated cathode materials currently reported and thus are considered as the most promising candidate for next-generation high-energy density Li-ion batteries. However, the rapid voltage decay and the irreversible phase transition of O3-type Li-rich cathode materials often lessen their actual energy density and limit their practical applications, and thus, effectively suppressing the voltage decay of Li-rich cathodes becomes the hotspot of the current research. Herein, the F-doped O2-type Li-rich cathode materials Li1.2Mn0.54Ni0.13Co0.13O2+δ-xFx (F-O2-LRO) are designed and prepared based on the P2-type sodium-ion cathode materials Na5/6Li1/4(Mn0.54Ni0.13Co0.13)3/4O2+δ (Na-LRO) by ion exchange. It has been found that the as-prepared F-O2-LRO exhibits excellent electrochemical performance, for example, a high discharge specific capacity of 280 mA h g-1 at 0.1 C with an initial Coulombic efficiency of 94.4%, which is obviously higher than the original LRO (77.2%). After 100 cycles, the F-O2-LRO cathode can still maintain a high capacity retention of 95% at a rate of 1 C, while the capacity retention of the original LRO is only 69.1% at the same current rate. Furthermore, the voltage difference (ΔV) of F-O2-LRO before and after cycling is only 0.268 V after 100 cycles at 1 C, which is less than that of the LRO cathode (0.681 V), indicating much lower polarization. Besides, even at a high current rate of 5 C, F-O2-LRO still displays a satisfactory discharge capacity of 210 mA h g-1 with a capacity retention of 90.1% after 100 cycles. Therefore, this work put forward a new strategy for the development and industrial application of Li-rich cathode materials in high-energy Li-ion batteries.

2.
Life Sci ; : 119505, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33872662

RESUMO

PURPOSE: We aimed to investigate the patterns and prognostic roles of tumor mutation burden and immune microenvironment in pancreatic cancer. METHODS: The somatic mutation data, transcriptome profiles and clinical information were downloaded from the Cancer Genome Atlas database. Gene expression difference, Gene ontology, KEGG, gene set enrichment analyses and "CIBERSORT" algorithm were performed to screen differentially expressed genes, enriched functions or pathways and immune infiltrates differences between high and low TMB groups. Single sample gene set enrichment and unsupervised consensus clustering analyses were used for immunity grouping. Immune cell infiltration and expressions of HLA and checkpoint genes were investigated. Finally, a nomogram model integrating TMB and immune infiltration was established. RESULTS: A total of 608 differentially expressed genes were identified between high and low TMB groups, KEGG base excision repair and DNA replication pathways were enriched in high TMB group. Infiltration levels of M0 macrophages were higher and dendritic resting cells were lower in high TMB group. The risk model based on TMB-related immune genes, FAM19A2 and SLC22A17 was established and high risk scores indicated poorer prognosis. The expressions of HLA genes and immune checkpoint genes were higher in high immunity group. The nomogram showed remarkable ability for individualized survival estimation with good AUC values (0.794 and 0.800, respectively) for 3- and 5-year survival rates prediction. CONCLUSIONS: The characteristics of tumor mutation burden and immune infiltration in pancreatic cancer provide new insights into the tumor microenvironment, immunotherapies and a novel prognostic nomogram model for pancreatic cancer patients.

3.
Huan Jing Ke Xue ; 42(2): 883-890, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742883

RESUMO

To improve the removal efficiency of dissolved organic matter in wastewater treatment plant (WWTP) effluent, electro-hybrid ozonation-coagulation (E-HOC) is proposed and the treatment characteristics and removal mechanism for WWTP effluent and ibuprofen (IBP) are investigated. The E-HOC process has a better removal effect on dissolved organic matter in WWTP effluent, achieving 46.4%, 20.0%, 19.4%, 36.1%, and 49.7% higher removal than EC, ozonation, pre-ozonation-EC, electrocoagulation-ozonation, and chemical coagulation, respectively. To determine the mechanism of the E-HOC process, quenching experiments and electron paramagnetic resonance (EPR) were conducted, which confirmed that metal coagulants can be used as a catalyst to effectively increase the generation of the hydroxyl radical (·OH). Synergistic effects between ozone and the coagulants (SOC) were also found to be involved. Fourier-transform infrared spectroscopy (FT-IR) illustrated that the surface hydroxyl groups of the coagulant (hydrolyzed species produced by Al anode electrolysis) were the active sites for the generation of·OH in the SOC reaction. Based on a kinetics analysis of organic matter removal in the E-HOC system, SOC effects and ozonation played dominant roles in the E-HOC process. Additionally, the SOC created a new pathway for·OH formation.

4.
Nanoscale ; 13(9): 5125-5135, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33651054

RESUMO

Photothermal therapy (PTT) is a promising tumor treatment modality, but its efficacy is strictly hindered by abnormally upregulated heat shock proteins (HSPs) in tumor cells under heat stress. Herein, we developed a flower-like MnO2-coated polydopamine (PDA@MnO2) core-shell nanoplatform with the surface adsorption of HSP70-silencing DNAzyme (DZ) for enhanced PPT. The PDA core acted as a robust photothermal agent, and also as a reductant to allow the surface growth of MnO2via an in situ reduction of KMnO4. The MnO2 shell enabled a rapid and efficient adsorption of DZ, and more importantly, acted as a metal reservoir to release Mn2+ in response to intracellular stimuli for the in situ activation of DZ, which addressed the key limitation of DZ for biological applications, i.e., metal-dependent activity. As a result, HSP70 was remarkably suppressed for improved PTT efficacy upon laser irradiation, which was explicitly demonstrated both in vitro and in vivo. Upon intravenous injection, the nanosystem could effectively accumulate in the tumor, and impose potent PTT for complete tumor elimination via inducing tumor cell apoptosis, but without any noticeable toxicity. This work provides a promising nanosystem for enhanced PTT via silencing resistance-related genes, and offers ideas for the design of self-activated gene therapy platforms using DZ.

6.
J Innate Immun ; : 1-15, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789297

RESUMO

Neutrophils express the two formyl peptide receptors (FPR1 and FPR2) and the medium-chain fatty acid receptor GPR84. The FPRs are known to define a hierarchy among neutrophil G protein-coupled receptors (GPCRs), that is, the activated FPRs can either suppress or amplify GPCR responses. In this study, we investigated the position of GPR84 in the FPR-defined hierarchy regarding the activation of neutrophil nicotine adenine dinucleotide phosphate (NADPH) oxidase, an enzyme system designed to generate reactive oxygen species (ROS), which are important regulators in cell signaling and immune regulation. When resting neutrophils were activated by GPR84 agonists, a modest ROS release was induced. However, vast amounts of ROS were induced by these GPR84 agonists in FPR2-desensitized neutrophils, and the response was inhibited not only by a GPR84-specific antagonist but also by an FPR2-specific antagonist. This suggests that the amplified GPR84 agonist response is achieved through a reactivation of desensitized FPR2s. In addition, the GPR84-mediated FPR2 reactivation was independent of ß-arrestin recruitment and sensitive to a protein phosphatase inhibitor. In contrast to FPR2-desensitized cells, FPR1 desensitization primarily resulted in a suppressed GPR84 agonist-induced ROS response, indicating a receptor hierarchical desensitization of GPR84 by FPR1-generated signals. In summary, our data show that the two FPRs in human neutrophils control the NADPH oxidase activity with concomitant ROS production by communicating with GPR84 through different mechanisms. While FPR1 desensitizes GPR84 and by that suppresses the release of ROS induced by GPR84 agonists, amplified ROS release is achieved by GPR84 agonists through reactivation of the desensitized FPR2.

7.
Phytother Res ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657655

RESUMO

Inflammation can cause a series of inflammatory lung disease, which seriously endangers human health. Pulmonary fibrosis is a kind of inflammatory disease with end-stage lung pathological changes. It has complicated and unknown pathogenesis and is still lack of effective therapeutic drugs. LPS-induced inflammation is a common feature of many infectious inflammations such as pneumonia, bacteremia, glomerulonephritis, etc. Evodiamine, one of the main components of Evodia rutaecarpa, is an alkaloid with excellent antiinflammatory effects. In this study, we evaluated the protective capacities of evodiamine on LPS-induced inflammatory damages in vitro and in vivo. MTT method, flow cytometry, immunofluorescence, and other methods were used for in vitro study to determine the protective capacities of evodiamine. The results suggest that evodiamine can protect murine macrophages from the LPS-nigericin-induced damages by (a) inhibiting cellular apoptosis, (b) inhibiting inflammatory cytokines releasing, and (c) activating the apelin pathway. We also used the exogenous apelin-13 peptide co-cultured with LPS-nigericin in RAW264.7 cells and found that apelin-13 contributes to protecting the effects of evodiamine. In vivo, the ELISA method and immunohistochemistry were used to examine inflammatory cytokines, apelin, and histological changes. BALB/c mice were exposed to LPS and subsequent administration of evodiamine (p.o.)for some time, the results of the alveolar lavage fluid and the tissue slices showed that evodiamine treatment alleviated the pulmonary inflammation and fibrosis, stimulated apelin expression and inhibited the inflammatory cytokines. These results provide a basis for the protective effect and mechanism of evodiamine in LPS-induced inflammation and suggest that it might be potential therapeutics in human pulmonary infections.

8.
Acta Pharmacol Sin ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547374

RESUMO

Astrocytes are multifunctional brain cells responsible for maintaining the health and function of the central nervous system. Accumulating evidence suggests that astrocytes might be complementary source across different brain regions to supply new neurons during adult neurogenesis. In this study, we found that neonatal mouse cortical astrocytes can be directly converted into neurons when exposed to neurogenic differentiation culture conditions, with insulin being the most critical component. Detailed comparison studies between mouse cortical astrocytes and neuronal progenitor cells (NPCs) demonstrated the converted neuronal cells originate indeed from the astrocytes rather than NPCs. The neurons derived from mouse cortical astrocytes display typical neuronal morphologies, express neuronal markers and possess typical neuronal electrophysiological properties. More importantly, these neurons can survive and mature in the mouse brain in vivo. Finally, by comparing astrocytes from different brain regions, we found that only cortical astrocytes but not astrocytes from other brain regions such as hippocampus and cerebellum can be converted into neurons under the current condition. Altogether, our findings suggest that neonatal astrocytes from certain brain regions possess intrinsic potential to differentiate/transdifferentiate into neurons which may have clinical relevance in the future.

9.
Org Lett ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533626

RESUMO

A highly regioselective nickel/Lewis acid catalyzed amination/cyclization of ynamide-nitriles with amines involving ß-addition has been developed. The reaction offers an attractive and efficient route for the synthesis of 3-aminoindoles and 4-aminoisoquinoline derivatives. The Ts-group on the ynamide acts as a directing group to produce the alkenyl nickel species with high regioselectivity.

10.
J Phys Chem Lett ; : 2133-2141, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625855

RESUMO

Two-dimensional (2D) layered hybrid perovskites provide an ideal platform for studying the properties of excitons. Here, we report on a strong triplet-exciton and longitudinal-optical (LO) phonon coupling in 2D (C6H5CH2CH2NH3, PEA)2PbBr4 perovskites. The triplet excitons exhibit strong photoluminescence (PL) in thick perovskite microflakes, and the PL is not detectable for monolayer microflakes. The coupling strength of the triplet exciton-LO phonon is approximately two to three times greater than that of the singlet exciton-LO phonon with a LO phonon energy of about 21 meV. This difference might due to the different locations of singlet excitons located in the well and triplet excitons located in the barrier in the 2D layered perovskite. Revealing the strong coupling of triplet exciton-LO phonon provides a fundamental understanding of many-body interaction in hybrid perovskites, which is useful to develop and optimize the optoelectronic devices based on 2D perovskites in the future.

11.
Sci Rep ; 11(1): 3863, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594193

RESUMO

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.


Assuntos
/diagnóstico , Programas de Rastreamento , Modelos Biológicos , Pneumonia/diagnóstico , /fisiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
12.
J Clin Lab Anal ; : e23740, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616216

RESUMO

BACKGROUND: Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers. METHODS: The singleton pregnant women (20-36 gestational weeks) with PE-related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI-C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy-associated plasma protein-A2 (PAPP-A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc). RESULTS: Of the 196 recruited subjects, 25% (n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative (n = 147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc, and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. CONCLUSIONS: The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre-defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.

13.
Cognition ; 211: 104619, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33601018

RESUMO

Speech prosody plays an important role in communication of meaning. The cognitive and computational mechanisms supporting this communication remain to be understood, however. Prosodic cues vary across talkers and speaking conditions, creating ambiguity in the sound-to-meaning mapping. We hypothesize that listeners ameliorate this ambiguity in part by learning talker-specific statistics of prosodic cues. To test this hypothesis, we investigate the production and recognition of question vs. statement prosody in American English. Experiment 1 elicits productions of questions and statements from 65 talkers to examine the distributional statistics characterizing within- and cross-talker variability in these productions. We use Bayesian ideal observer models to assess the predicted consequences of cross-talker variability on listeners' recognition of prosody. We find that learning of talker-specific distributional statistics is predicted to facilitate recognition, above and beyond what can be achieved via commonly assumed normalizations of prosodic cues. Experiment 2 tests this prediction in a comprehension experiment. We expose different groups of listeners to different prosodic input statistics and assess listeners' recognition of questions and statements both prior to, and following, exposure. Prior to exposure, ideal observer-derived predictions based on Experiment 1 provide a good qualitative fit against listeners' recognition of prosodic contours in Experiment 2. Following exposure, listeners shift the categorization boundary between questions and statements in ways consistent with learning of talker-specific statistics.

14.
Org Lett ; 23(3): 1090-1095, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428411

RESUMO

A gold-catalyzed cyclization of aniline-tethered furan-ynones has been developed. The reaction proceeds via trapping of the resulting stabilized cationic intermediate with an amide group leading to polycycles featured with a spiro-cyclohexadienone-hydrofuran framework with high efficiency. The resulting N-alkyl products undergo photorearrangements to afford the ring-enlarged benzo[b]azepine derivatives or iron-promoted novel rearrangement to diketone-containing spirocycles involving multiple C-X bond cleavages and formations.

15.
Ying Yong Sheng Tai Xue Bao ; 32(1): 289-298, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477237

RESUMO

Evapotranspiration is the key element of hydrological energy cycle and climate system. It is of great significance to estimate the spatiotemporal variation of evapotranspiration and its response to climate and land use changes for understanding the effects of water cycle and ecological processes in urban basins. Based on the three-temperature model and MODIS Image, we estimated and analyzed the spatiotemporal variation of evapotranspiration in Nanning City from 2001 to 2018, and examined the influence and driving mode of main climate factors and land use types on evapotranspiration. The results showed that the annual average evapotranspiration of Nanning City ranged from 495.7 to 781.1 mm during 2001-2018, with the inter annual relative variability ranging from -22.5% to 23.1%, showing an overall upward trend. The regional evapotranspiration showed a distribution pattern of high north-south and low middle, with the urban evapotranspiration being significantly lower than suburban area. The evapotranspiration had a significant multiple correlation with climate factors. The influence of temperature on the evapotranspiration was stronger than precipita-tion. Evapotranspiration was temperature driven in suburbs, but was driven by multiple factors in urban area. The average evapotranspiration of different land use types in Nanning was forests (823.4 mm) > grasslands (675.6 mm) > croplands (582.9 mm) > urban area (346.6 mm). The change of land use type was the main underlying surface factor leading to the significant change of regional evapotranspiration.


Assuntos
Clima , Florestas , China , Temperatura , Ciclo Hidrológico
16.
J Glob Antimicrob Resist ; 24: 266-269, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33476836

RESUMO

OBJECTIVES: The global spread of the New Delhi metallo-ß-lactamase 1 (NDM-1) gene poses a significant challenge to worldwide public health. Here, we characterize the whole genome of NDM-1-producing Proteus mirabilis isolate SNYG35 of broiler chicken origin in China. METHODS: The genome of SNYG35 was sequenced using a PacBio RS II sequencing instrument and Illumina HiSeq platform. SMRT cell data were assembled independently using HGAP4 and Canu v1.6, and were further polished with Illumina data using Pilon v1.22. The presence of antimicrobial resistance genes was identified using CGE ResFinder 3.2. A conjugation experiment was performed using the sodium azide-resistant Escherichia coli J53AziR strain as the recipient. RESULTS: The chromosome of SNYG35 is 4 014 504 bp in size and consists of one chromosome and one plasmid named pSNYG35. It contains 3646 coding sequences, 82 tRNA genes, 22 rRNAs, and four non-coding RNAs. Besides blaNDM-1, SNYG35 harbours 26 different antimicrobial resistance genes including ESBL gene blaCTX-M-65 as well as fluoroquinolone and aminoglycoside resistance gene aac(6')-Ib-cr. The blaNDM-1-harbouring pSNYG35 is a pPrY2001-like plasmid and shares highest nucleotide identity to pHFK418-NDM. It carries a Tn1696-like multidrug-resistant region harbouring 12 different antimicrobial resistance genes, and could be transferred to E. coli J53. CONCLUSIONS: Here, we report for the first time the whole genome sequence of a NDM-1-producing P. mirabilis isolate from broiler chicken in China, which provides valuable information for tracing the potential transmission of NDM-1-producing P. mirabilis from broiler chicken to humans, as well as revealing the spread and evolution of blaNDM-1-harbouring pPrY2001-like plasmids.

17.
Plant J ; 106(1): 200-213, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33432631

RESUMO

SPLAYED (SYD) is a SWItch/Sucrose Non-Fermentable (SWI/SNF)-type chromatin remodeler identified in Arabidopsis thaliana (Arabidopsis). It is believed to play both redundant and differential roles with its closest homolog BRAHMA (BRM) in diverse plant growth and development processes. To better understand how SYD functions, we profiled the genome-wide occupancy of SYD and its impact on the global transcriptome and trimethylation of histone H3 on lysine 27 (H3K27me3). To map the global occupancy of SYD, we generated a GFP-tagged transgenic line and used it for chromatin immunoprecipitation experiments followed by next-generation sequencing, by which more than 6000 SYD target genes were identified. Through integrating SYD occupancy and transcriptome profiles, we found that SYD preferentially targets to nucleosome-free regions of expressed genes. Further analysis revealed that SYD occupancy peaks exhibit five distinct patterns, which were also shared by BRM and BAF60, a conserved SWI/SNF complex component, indicating the common target sites of these SWI/SNF chromatin remodelers and the functional relevance of such distinct patterns. To investigate the interplay between SYD and Polycomb-group (PcG) proteins, we performed a genome-wide analysis of H3K27me3 in syd-5. We observed both increases and decreases in H3K27me3 levels at a few hundred genes in syd-5 compared to wild type. Our results imply that SYD can act antagonistically or synergistically with PcG at specific genes. Together, our SYD genome-wide occupancy data and the transcriptome and H3K27me3 profiles provide a much-needed resource for dissecting SYD's crucial roles in the regulation of plant growth and development.

18.
J Med Virol ; 93(6): 3508-3515, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33410516

RESUMO

Influenza virus cause seasonal influenza epidemic and seriously sporadic influenza pandemic outbreaks. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Variation in the sialic acid receptor binding site leads to strain-specific binding and results in different binding modes to the host receptors. Here, we evaluated the neutralizing activity and hemagglutination inhibition activity of a prepared murine anti-H1N1 monoclonal antibody PR8-23. Then we identified the epitope peptide of antibody PR8-23 by phage display technique from phage display peptide libraries. The identified epitope, 63-IAPLQLGKCNIA-74, containing two α-helix and two ß-fold located at the footprint of the sialoglycan receptor on the RBS in the globular head domain of HA. It broads the growing arsenal of motifs for the amino acids on the globular head domain of HA in sialic acid receptor binding site and neutralizing antibody production.

19.
Phytomedicine ; 80: 153383, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33091855

RESUMO

BACKGROUND: Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) is a natural polyphenolic ester isolated as a minor component from a water extract of the Chinese medicine Zhongjiefeng [Sarcandra glabra (Thunb.) Nakai (Chloranthaceae)] and has previously shown to have activity against solid tumors through the modulation of multiple targets or signal pathways. However, the activity and potential mechanism of CADPE against leukemia cells have not yet been characterized. PURPOSE: To investigate whether and how CADPE kills leukemia cells. METHOD: (1) The activity of CADPE inhibiting the growth of different leukemia cell lines was evaluated by MTT assay; (2) Cell cycle arrest and apoptosis induced by CADPE were determined by flow cytometry with FlowJo software for quantification; (3) The protein levels were analyzed by Western blot and ubiquitin-binding c-Myc was acquired by co-immunoprecipitation. RESULTS: CADPE exerted potent activity against different leukemia cell lines with low toxicity in normal cells. In terms of mechanism of action, CADPE promoted ubiquitin-proteasome-dependent degradation of c-Myc through activating glycogen synthase kinase-3ß (GSK3ß) and downregulating deubiquitinating enzyme USP28 to trigger the interaction of c-Myc with ubiquitin ligase Fbw7, resulting in the downregulation of cell cycle regulators and anti-apoptotic proteins and consequently, cell cycle arrest and cell apoptosis. CONCLUSION: CADPE is a novel c-Myc inhibitor with high activity and a unique mechanism for killing leukemia cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Leucemia/tratamento farmacológico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas F-Box/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Leucemia/metabolismo , Leucemia/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ubiquitina/metabolismo , Ubiquitina Tiolesterase/metabolismo
20.
J Affect Disord ; 278: 311-319, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979562

RESUMO

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Microbioma Gastrointestinal , Transtorno Bipolar/genética , Estudos Transversais , Transtorno Depressivo Maior/genética , Microbioma Gastrointestinal/genética , Humanos , Metagenômica , Triptofano
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