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1.
Circulation ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686562

RESUMO

BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.

2.
Gut ; 73(2): 268-281, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37734910

RESUMO

BACKGROUND AND AIMS: Deregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m6A demethylases, in patients with ulcerative colitis (UC). METHODS: We analysed colon tissues of Ftoflox/flox; Villin-cre mice and their Ftoflox/flox littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C16-ceramide. RESULTS: FTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Ftoflox/flox;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m6A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment. CONCLUSIONS: FTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m6A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.


Assuntos
Colite Ulcerativa , Colite , Humanos , Animais , Camundongos , Colite Ulcerativa/metabolismo , RNA Ribossômico 16S/metabolismo , Mucosa Intestinal/metabolismo , Colite/induzido quimicamente , Colite/genética , Colo/metabolismo , Esfingolipídeos/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
3.
Small ; 20(2): e2305085, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37661574

RESUMO

Lithium (Li) metal batteries are highly sought after for their exceptional energy density. However, their practical implementation is impeded by the formation of dendrites and significant volume fluctuations in Li, which stem from the uneven distribution of Li-ions and uncontrolled deposition of Li on the current collector. Here, an amino-functionalized reduced graphene oxide covered with polyacrylonitrile (PrGN) film with an electric field gradient structure is prepared to deal with such difficulties. This novel current collector serves to stabilize Li-metal anodes by regulating Li-ion flux through vertically aligned channels formed by porous polyacrylonitrile (PAN). Moreover, the amino-functionalized reduced graphene oxide (rGN) acts as a three-dimensional (3D) host, reducing nucleation overpotential and accommodating volume expansion during cycling. The combination of the insulating PAN and conducting rGN creates an electric field gradient that promotes a bottom-up mode of Li electrodeposition and safeguards the anode from interfacial parasitic reactions. Consequently, the electrodes exhibit exceptional cycle life with stable voltage profiles and minimal hysteresis under high current densities and large areal capacities.

4.
Org Biomol Chem ; 22(25): 5112-5116, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38864433

RESUMO

An air-stable quinoline-derived NNP ligand chelated Mn catalyst was developed for the efficient α-alkylation of ketones with primary alcohols via a hydrogen auto-transfer methodology. The sole by-product formed is water, rendering the protocol atom efficient. A wide range of ketone and alcohol substrates were employed, providing the α-alkylated ketones with isolated yields up to 94%. This system was also efficient for the green synthesis of quinoline derivatives while using (2-aminophenyl)methanol as an alkylating reagent.

5.
Nano Lett ; 23(4): 1600-1607, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36626315

RESUMO

Metal-Organic frameworks (MOFs) are increasingly being investigated for the synthesis of carbon-supported metal-based ultrafine nanoparticles (UNPs). However, the collapse of the carbon framework and aggregation of metal particles in the pyrolysis process have severely hindered their stability and applications. Here, we report the synchronous nucleation pseudopyrolysis of MOFs to confine Fe/FeOx UNPs in intact porous carbon nanorods (IPCNs), revealed by in situ transmission electron microscopy experiments and ex situ structure analysis. The pseudopyrolysis mechanism enables strong physical and chemical confinement effects between UNPs and carbon by moderate thermal kinetics and abundant oxygen defects. Further, this strong confinement is greatly beneficial for subsequent chemical transformations to obtain different Fe-based UNPs and excellent electrochemical performance. As a proof of concept, the as-prepared FeSe UNPs in IPCNs show superior lithium storage performance with an ultrahigh and stable capacity of 815.1 mAh g-1 at 0.1 A g -1 and 379.7 mAh g-1 at 5 A g-1 for 1000 cycles.

6.
Crit Rev Food Sci Nutr ; : 1-19, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655428

RESUMO

Lycopene is a promising biological functional component with various biological activities and excellent pharmacological activities. However, its low water solubility and stability lead to low oral bioavailability, which limits its edible and medicinal research. Then, it is necessary to explore effective methods to protect lycopene from destruction and further exploit its potential benefits. The absorption of lycopene in vivo is affected by solubility, stability, isomer type, emulsifying ability, difficulty in forming micelles in vivo, and interaction with food components. Emulsions, pickering emulsions, micelles, liposomes, bigels, beasds, solid dispersions, microcapsules, nanoparticles, electrospinning and other drug delivery systems can be used as good strategies to improve the stability and bioavailability of lycopene. In this paper, the absorption process of lycopene in vivo and the factors affecting its bioavailability were discussed, and the preparation strategies for improving the stability, bioavailability, and health benefits of lycopene were reviewed, to provide some clues and references for the full utilization of lycopene in the field of health. However, there are still various unresolved mysteries regarding the metabolism of lycopene. The safety and in vivo studies of various preparations should be further explored, and the above technologies also face the challenge of industrial production.

7.
Int J Equity Health ; 22(1): 213, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821887

RESUMO

BACKGROUND: Physio-psycho-socioeconomical health comprehensively declines during aging, the complexity of which is challenging to measure. Among the complexity, multiple chronic disorders continuously cumulated during aging, further aggravating the challenge. METHODS: A population-based survey on Comprehensive Ageing Health Assessment was conducted in older adults (age > = 60) enrolled from hospital settings and community settings in 13 working centers in six subnational regions in China. Cross-sectional datasets of 8,093 older participants with approximately complete assessment results were collected for the present analysis. Individual's multi-disease or multi-symptom was respectively scored by summing coexistent multiple diseases or multiple symptoms by respective weighting efficient for Self-Rated Health (SRH). Individual's age-dependent health decline was further summed of four SRH-weighted scores for daily function (activity of daily life, ADL), physical mobility (an average of three metrics), cognitive function (mini mental state examination, MMSE) and mental being (geriatric depression scale, GDS) plus multi-disease score (MDS) and multi-symptom score (MSS).Multi-disease patten among 18 diseases or multi-symptom pattern among 15 symptoms was latent-clustered in the older adults, the optimal outcome of which was categorized into high, moderate or low aging-associated clusters, respectively. Percentage distribution was compared between overall health decline score and multi-disease pattern cluster or multi-symptom patten cluster. A new variable of difference between MDS and MSS (hereinafter terming DMM) that displayed linear variation with socioeconomic factors was further fitted using multilevel regression analyses by substantial adjustments on individual confounders (level-1) and subnational region variation (level-2). RESULTS: Consistent gradient distribution was shown between health decline and multimorbidity pattern cluster in the older adults. DMM was found linearly varied with personal education attainment and regional socioeconomic status. Using optimally fitted stratification of DMM (DMM interval = 0.02), an independent U-shaped interrelated tendency was shown between health decline, multi-disease and multi-symptom, which could be well explained by regional disparities in socioeconomic status. CONCLUSION: Newly developed metrics for age-dependent health decline and aging-associated multimorbidity patten were preliminarily validated from within. The new variable of optimally fitted categorization of DMM might function as a practical indicator aiding in improving the cost-effectiveness and reduce inequity of healthcare delivery for older adults in developing countries.


Assuntos
Envelhecimento , Países em Desenvolvimento , Humanos , Idoso , Estudos Transversais , Análise Custo-Benefício , Envelhecimento/psicologia , Atenção à Saúde
8.
Macromol Rapid Commun ; 44(3): e2200693, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36250510

RESUMO

Multiple and two-way reversible shape memory polymers (M/2W-SMPs) are highly promising for many fields due to large deformation, lightweight, strong recovery stress, and fast response rates. Herein, a semi-crystalline block poly(urethane-urea-amide) elastomers (PUUAs) are prepared by the copolymerization of isocyanate-terminated polyurethane (OPU) and amino-terminated oligomeric polyamide-1212 (OPA). PUUAs, composed of OPA as stationary phase and PTMEG as reversible phase, exhibit excellent rigidity, flexibility, and resilience, and cPUUA-C7 -S25 exhibits the best tensile property with strength of 10.3 MPa and elongation at break of 360.2%. Besides, all the PUUAs possess two crystallization/melting temperatures and a glass transition temperature, which endow PUUAs with multiple and reversible two-way shape memory effect (M/2W-SME). Physically crosslinked PUUA-C0 -S25 exhibits excellent dual and triple shape memory, and micro chemically crosslinked cPUUA-C7 -S25 further shows quadruple shape memory behavior. Additionally, both PUUA-C0 -S25 and cPUUA-C7 -S25 have 2W-SME. Intriguingly, cPUUA-C7 -S25 can achieve a higher temperature (up to 165 °C) SME, which makes it suitable for more complex and changeable applications. Based on the advantages of M/2W-SME, a temperature-responsive application scenario where PUUAs can transform spontaneously among different shapes is designed. These unique M/2W-SME and high-temperature SME will enable the applications of high-temperature sensors, actuators, and aerospace equipment.


Assuntos
Elastômeros , Polímeros , Polímeros/química , Amidas , Ureia , Poliuretanos/química
9.
Pharmazie ; 78(11): 225-230, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178283

RESUMO

New anti- Toxoplasma gondii agents are in demand due to the emergence of high toxicity. Ginseng polysaccharides and saponins can be used to treat the replication of Toxoplasma gondii in an attempt to determine whether the medicinal uses of ginseng are supported by pharmacological effects. Anti- Toxoplasma gondii activities of ginseng polysaccharides and saponins were examined in vitro and in vivo. The findings are the survival time and rate of Toxoplasma gondii infected mice after the intake of the total polysaccharides and saponins increased compared to untreated control mice. The survival rate of mice treated with ginseng saponins was the highest at 83.3%, the phenomenon of splenomegaly of mice was decreased especially ( p < 0.05) treated with ginseng polysaccharides. Accordingly, ginseng polysaccharides and saponins have a potential application in anti-Toxoplasma gondii treatments.


Assuntos
Panax , Saponinas , Toxoplasma , Animais , Camundongos , Saponinas/farmacologia , Polissacarídeos/farmacologia
10.
BMC Bioinformatics ; 23(Suppl 5): 249, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131234

RESUMO

BACKGROUND: The technologies advances of single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) allowed to generate thousands of single cells in a relatively easy and economic manner and it is rapidly advancing the understanding of the cellular composition of complex organisms and tissues. The data structure and feature in scRNA-seq is similar to that in scATAC-seq, therefore, it's encouraged to identify and classify the cell types in scATAC-seq through traditional supervised machine learning methods, which are proved reliable in scRNA-seq datasets. RESULTS: In this study, we evaluated the classification performance of 6 well-known machine learning methods on scATAC-seq. A total of 4 public scATAC-seq datasets vary in tissues, sizes and technologies were applied to the evaluation of the performance of the methods. We assessed these methods using a 5-folds cross validation experiment, called intra-dataset experiment, based on recall, precision and the percentage of correctly predicted cells. The results show that these methods performed well in some specific types of the cell in a specific scATAC-seq dataset, while the overall performance is not as well as that in scRNA-seq analysis. In addition, we evaluated the classification performance of these methods by training and predicting in different datasets generated from same sample, called inter-datasets experiments, which may help us to assess the performance of these methods in more realistic scenarios. CONCLUSIONS: Both in intra-dataset and in inter-dataset experiment, SVM and NMC are overall outperformed others across all 4 datasets. Thus, we recommend researchers to use SVM and NMC as the underlying classifier when developing an automatic cell-type classification method for scATAC-seq.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação , Análise de Célula Única , Cromatina/genética , Aprendizado de Máquina , Análise de Célula Única/métodos
11.
J Am Chem Soc ; 144(22): 9817-9826, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35617524

RESUMO

Photoinduced atom transfer radical polymerization (ATRP) has been proved to be a versatile technique for polymer network formation. However, the slow polymerization rates of typical ATRP limited its application in the field of additive manufacturing (3D printing). In this work, we introduced carbon quantum dots (CQDs) for the first time to the ATRP in aqueous media and developed an ultrafast visible-light-induced polymerization system. After optimization, the polymerization could achieve a high monomer conversion (>90%) within 1 min, and the polydispersity index (PDI) of the polymer was lower than 1.25. This system was then applied as the first example of ATRP for the 3D printing of hydrogel through digital light processing (DLP), and the printed object exhibited good dimensional accuracy. Additionally, the excellent and stable optical properties of CQDs also provided interesting photoluminescence capabilities to the printed objects. We deduce this ATRP mediated 3D printing process would provide a new platform for the preparation of functional and stimuli-responsive hydrogel materials.

12.
Small ; 18(7): e2105866, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34878213

RESUMO

A nitrogen-doped carbon bubble-carbon nanotube@red phosphorus (N-CBCNT@rP) network composite is fabricated, featuring an rP film embedded in a highly N-doped CBCNT network with hierarchical pores of different sizes and interior void spaces. Highly N-doped CBCNT with an optimized structure is utilized to achieve an ultrahigh rP content of 53 wt% in the N-CBCNT@rP composite by the NP bond, which shows a record rP content for rP-carbon composites by the vaporization-condensation process. When tested as an anode for lithium-ion batteries, the N-CBCNT@rP composite exhibits an ultrahigh initial Coulombic efficiency of 87.5%, high specific capacity, outstanding rate performance, and superior cycling stability at a high current density (capacity decay of 0.011% per cycle over 1500 cycles at 5 A g-1 ), which is the lowest capacity fading rate of those previously reported for rP-based electrodes. The superior lithium-ion storage performance of the N-CBCNT@rP composite electrode is primarily attributed to its structure. The 3D hierarchical conducting network of the N-CBCNT@rP composite with abundant N-P bonds endows the entire electrode with maximized conductivity for superior ion and electron transfer kinetics. Moreover, N-CBCNT networks with hierarchical pores of different sizes can fix the location of rP, prevent agglomeration, and avoid volume expansion of rP.

13.
Small ; 18(41): e2203948, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36084223

RESUMO

The poor conductivity, inert charge transmission efficiency, and irreversible Na+ trapping of Na2 Ti3 O7 result in retardant electrons/ions transportation and deficient sodium-ion storage efficiency, leading to sluggish reaction kinetics. To address these issues, an urchin-like Ti2 CTx /Na2 Ti3 O7 (Ti2 C/NTO) heterostructure sphere consisting of Ti2 C/NTO heterostructure nanobelts array is developed via a facile one-step in situ hydrothermal strategy. The Ti2 C/NTO heterostructure can obviously decrease Na+ diffusion barriers and increase electronic conductivity to improve reaction kinetics due to the built-in electric field effect and high-quantity interface region. In addition, the urchin-like vertically aligned nanobelts can reduce the diffusion distance of electrons and ions, provide favored electrolyte infiltration, adapt large volume expansion, and mitigate the aggregation to maintain structural stability during cycles, further enhancing the reaction kinetics. Furthermore, the Ti2 C/NTO heterostructure can effectively suppress many unwanted side reactions between reactive surface sites of NTO and electrolyte as well as irreversible trapping of Na+ . As a result, systematic electrochemical investigations demonstrate that the Ti2 C/NTO heterostructure as an anode material for record sodium-ion storage delivers the highest reversible capacity, the best cycling stability with 0.0065% decay rate for 4500 cycles at 2.0 A g-1 , and excellent rate capability of 172.1 mAh g-1 at 10.0 A g-1 .

14.
Bioinformatics ; 37(20): 3642-3644, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33830205

RESUMO

SUMMARY: JavaScript-based Circos libraries have been widely implemented to generate interactive Circos plots in web applications. However, these libraries require either local installation, which requires the compilation of extra libraries, or extra data processing procedures to prepare input and configuration for each track of plot, which limits the utility and capability of integration with powerful R packages. In this report, we present interacCircos, an R package for creating interactive Circos plots through the integration of JavaScript-based libraries. interacCircos can simply and flexibly implement 14 track-plot functions and 7 auxiliary functions for presenting large-scale genomic data in interactive Circos plots. AVAILABILITY AND IMPLEMENTATION: InteracCircos and its manual are freely available at https://github.com/mrcuizhe/interacCircos under the GPL license. The online documentation is available at https://mrcuizhe.github.io/interacCircos_documentation/index.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

15.
Acta Pharmacol Sin ; 43(9): 2362-2372, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35105957

RESUMO

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9-/-) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil-/-) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.


Assuntos
Ácidos e Sais Biliares , Fatores de Transcrição Kruppel-Like/metabolismo , Simportadores , Animais , Ácidos e Sais Biliares/metabolismo , Circulação Êntero-Hepática , Intestinos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Simportadores/metabolismo , Fatores de Transcrição/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6730-6740, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36604923

RESUMO

Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.


Assuntos
Quinase 3 da Glicogênio Sintase , Hiperalgesia , Camundongos , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Quinase 3 da Glicogênio Sintase/efeitos adversos , Quinase 3 da Glicogênio Sintase/metabolismo , Dor/tratamento farmacológico , Dor/induzido quimicamente , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Canais de Cátion TRPV/efeitos adversos
17.
BMC Bioinformatics ; 22(1): 552, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772337

RESUMO

BACKGROUND: With the rapid development of long-read sequencing technologies, it is possible to reveal the full spectrum of genetic structural variation (SV). However, the expensive cost, finite read length and high sequencing error for long-read data greatly limit the widespread adoption of SV calling. Therefore, it is urgent to establish guidance concerning sequencing coverage, read length, and error rate to maintain high SV yields and to achieve the lowest cost simultaneously. RESULTS: In this study, we generated a full range of simulated error-prone long-read datasets containing various sequencing settings and comprehensively evaluated the performance of SV calling with state-of-the-art long-read SV detection methods. The benchmark results demonstrate that almost all SV callers perform better when the long-read data reach 20× coverage, 20 kbp average read length, and approximately 10-7.5% or below 1% error rates. Furthermore, high sequencing coverage is the most influential factor in promoting SV calling, while it also directly determines the expensive costs. CONCLUSIONS: Based on the comprehensive evaluation results, we provide important guidelines for selecting long-read sequencing settings for efficient SV calling. We believe these recommended settings of long-read sequencing will have extraordinary guiding significance in cutting-edge genomic studies and clinical practices.


Assuntos
Benchmarking , Genômica , Testes Diagnósticos de Rotina , Variação Estrutural do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA
18.
Small ; 17(45): e2104186, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34622576

RESUMO

NiS1.23 Se0.77 nanosheets closely attached to the internal surface of hollow mesoporous carbon sphere (HMCS) to form a NiS1.23 Se0.77 nanosheets embedded in HMCS (NSSNs@HMCS) composite as the anode of sodium ion batteries (SIBs) is reported by a facile synthesis route. The anode exhibits a superior reversible capacity (520 mAh g-1 at 0.1 A g-1 ), impressive coulombic efficiency (CE) of up to 95.3%, a high rate capacity (353 mAh g-1 at 5.0 A g-1 ), excellent capacity retention at high current density (95.6%), and high initial coulombic efficiency (ICE) (95.1%). Firstly, the highest ICE for NiS2 /NiSe2 -based anode can be ascribed to ultrathin layered structure of NiS1.23 Se0.77 nanosheet and highly efficient electron transfer between the active material and HMCS. Secondly, the optimized NiS2 /NiSe2 heterostructure at the nanoscale of the inside HMCS is formed after the first discharge/charge cycles, which can provide rich heterojunction interfaces/boundaries of sulfide/selenides to offer faster Na+ pathways, decrease the Na+ diffusion barriers, increase electronic conductivity, and limit the dissolution of polysulfides or polyselenides in the electrolyte. Finally, the hollow structure of the HMCS accommodates the volume expansion, prevents the pulverization and aggregation issues of composite materials, which can also promote outstanding electrochemical performance.

19.
Bioinformatics ; 36(7): 2195-2201, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31782758

RESUMO

MOTIVATION: Integrative analysis of genomic data that includes statistical methods in combination with visual exploration has gained widespread adoption. Many existing methods involve a combination of tools and resources: user interfaces that provide visualization of large genomic datasets, and computational environments that focus on data analyses over various subsets of a given dataset. Over the last few years, we have developed Epiviz as an integrative and interactive genomic data analysis tool that incorporates visualization tightly with state-of-the-art statistical analysis framework. RESULTS: In this article, we present Epiviz Feed, a proactive and automatic visual analytics system integrated with Epiviz that alleviates the burden of manually executing data analysis required to test biologically meaningful hypotheses. Results of interest that are proactively identified by server-side computations are listed as notifications in a feed. The feed turns genomic data analysis into a collaborative work between the analyst and the computational environment, which shortens the analysis time and allows the analyst to explore results efficiently.We discuss three ways where the proposed system advances the field of genomic data analysis: (i) takes the first step of proactive data analysis by utilizing available CPU power from the server to automate the analysis process; (ii) summarizes hypothesis test results in a way that analysts can easily understand and investigate; (iii) enables filtering and grouping of analysis results for quick search. This effort provides initial work on systems that substantially expand how computational and visualization frameworks can be tightly integrated to facilitate interactive genomic data analysis. AVAILABILITY AND IMPLEMENTATION: The source code for Epiviz Feed application is available at http://github.com/epiviz/epiviz_feed_polymer. The Epiviz Computational Server is available at http://github.com/epiviz/epiviz-feed-computation. Please refer to Epiviz documentation site for details: http://epiviz.github.io/.


Assuntos
Genômica , Software , Genoma , Projetos de Pesquisa
20.
Langmuir ; 37(35): 10461-10468, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34431681

RESUMO

A colloidal nanocrystal cluster (CNC) is a hierarchical nanostructure formed by clustering several nanocrystals into one nano-ensemble, which may exhibit unique optical or catalytic properties different from individual nanocrystals owing to the mutual interactions among neighboring component nanocrystals. However, there is still no universal synthetic route that could be applicable to diverse material compositions with precisely controlled hierarchical structures (i.e., nanocrystal number density, component nanocrystal size, and overall diameter of the CNC) up to now. Herein, a general and novel synthetic strategy was reported for crafting a wide range of inorganic CNCs (i.e., noble metal, semiconductor, and metal oxide) via utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors prepared by sequential atom transfer radical polymerization. The hierarchical structure of rationally designed CNCs could be readily tailored by varying the P4VP molecular weight of star-like nanoreactors and the parameter optimization during the CNC preparation process, which was inaccessible by conventional synthetic methods.

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