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1.
Chem Sci ; 15(11): 4171-4178, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38487222

RESUMO

Achieving long-lived room-temperature phosphorescence from pure organic amorphous polymers is attractive, and afterglow materials with colour-tunable and multiple-stimuli-responsive afterglow are particularly important, but only few materials with these characteristics have been reported so far. Herein, a facile and general method is reported to construct a series of ε-polylysine (ε-PL)-based afterglow materials with tunable colour (from blue to red) and long life. By doping guest molecules into ε-PL to obtain composite materials, the polymer matrix provides a rigid environment for luminescent groups, resulting in amorphous polymers with different RTPs. In this system, the materials even have impressive humidity-stimulated responses, and the phosphorescence emission exhibits excitation-dependent and time-dependent properties. The humidity-responsive afterglow is caused by the destruction of hydrogen bonds and quenching of triplet excitons. The time-dependent afterglow should stem from the formation of diversified RTP emissive species with comparable but different lifetimes. 9,10-diaminophene has Ex-De properties in the film doping state. With the change of excitation wavelength (254 nm to 365 nm), the emission wavelength shifts from 461 nm to 530 nm, accompanied by the change of emission colour from blue to green. In addition, the phosphorescence life of the film is the longest, up to 2504.7 ms, and the afterglow lasts up to 15 s, which is conducive to its applications in anti-counterfeiting and information encryption.

2.
Heliyon ; 10(3): e24806, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314285

RESUMO

Cervical squamous cell carcinoma (CESC) ranks among the primary contributors to global cancer-associated mortality. However, the role mediated by synaptotagmin 7 (SYT7) in CESC remains unclear. Our study employed immunohistochemistry to assess the level of SYT7 expression in the tissue microarray. Furthermore, lentiviral shRNA transduction was utilized to establish SYT7 knockdown cell line models based on HeLa and SiHa cell lines. The functional impacts of silencing SYT7 expression in vitro were evaluated. A subcutaneous xenograft model was employed to examine the tumorigenic potential of cells with or without SYT7. The content of SYT7 in CESC tissues was significantly elevated compared to adjacent normal tissues. Functionally, silencing SYT7 in HeLa and SiHa cells suppressed cell proliferation, colony formation ability, and apoptosis enhancement. Additionally, cells with suppressed SYT7 also exhibited inhibited cell migration and invasion. In vivo experiments demonstrated the loss of tumorigenic ability in SYT7 knockdown cells and suppressed tumor growth. Quantitative PCR PrimeView PathArray and apoptosis antibody array analyses revealed that upon elimination of SYT7, there was a significant upregulation observed in Caspase 8, TNF-R1 (TNF receptor superfamily member 1A), and HSPA5 (heat shock protein family A [Hsp70] member 5), while TGFBI (transforming growth factor beta-induced), RPL31 (ribosomal protein L31), LUM (lumican), HSDL2 (hydroxysteroid dehydrogenase-like 2), ITGB5 (integrin subunit beta 5), and Smad2 (SMAD family member2) were downregulated. Overall, we have demonstrated the tumor-promoting functions of SYT7 in CESC.

3.
J Chem Phys ; 160(6)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38341796

RESUMO

We study the dynamics of the end monomers of a real chain confined in a spherical cavity to search for a small target on the cavity surface using Langevin dynamics simulation. The results are compared and contrasted with those of a Rouse chain to understand the influence of excluded volume interactions on the search dynamics, as characterized by the first passage time (FPT). We analyze how the mean FPT depends on the cavity size Rb, the target size a, and the degree of confinement quantified by Rg/Rb, with Rg being the polymer radius of gyration in free space. As a basic finding, the equilibrium distribution of the end monomers of a real chain in a closed spherical cavity differs from that of a Rouse chain at a given Rg/Rb, which leads to the differences between the mean FPTs of real and Rouse chains. Fitting the survival probability S(t) by a multi-exponential form, we show that the S(t) of real chains exhibits multiple characteristic times at large Rg/Rb. Our simulation results indicate that the search dynamics of a real chain exhibit three characteristic regimes as a function of Rg/Rb, including the transition from the Markovian to non-Markovian process at Rg/Rb ≈ 0.39, along with two distinct regimes at 0.39 < Rg/Rb < 1.0 and Rg/Rb > 1.0, respectively, where S(t) exhibits a single characteristic time and multiple characteristic times.

4.
J Chem Phys ; 160(4)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38265089

RESUMO

We utilized molecular dynamic simulation to investigate the glass formation of star polymer melts in which the topological complexity is varied by altering the number of star arms (f). Emphasis was placed on how the "confinement effect" of repulsive inter-arm interactions within star polymers influences the thermodynamics and dynamics of star polymer melts. All the characteristic temperatures of glass formation were found to progressively increase with increasing f, but unexpectedly the fragility parameter KVFT was found to decrease with increasing f. As previously observed, stars having more than 5 or 6 arms adopt an average particle-like structure that is more contracted relative to the linear polymer size having the same mass and exhibit a strong tendency for intermolecular and intramolecular segregation. We systematically analyzed how varying f alters collective particle motion, dynamic heterogeneity, the decoupling exponent ζ phenomenologically linking the slow ß- and α-relaxation times, and the thermodynamic scaling index γt. Consistent with our hypothesis that the segmental dynamics of many-arm star melts and thin supported polymer films should exhibit similar trends arising from the common feature of high local segmental confinement, we found that ζ increases considerably with increasing f, as found in supported polymer films with decreasing thickness. Furthermore, increasing f led to greatly enhanced elastic heterogeneity, and this phenomenon correlates strongly with changes in ζ and γt. Our observations should be helpful in building a more rational theoretical framework for understanding how molecular topology and geometrical confinement influence the dynamics of glass-forming materials more broadly.

5.
Nat Commun ; 14(1): 4164, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443149

RESUMO

Although room temperature phosphorescence (RTP) materials have been widely investigated, it is still a great challenge to improve the performance of RTP materials by promoting triplet exciton generation and stabilization. In this study, an in-situ derivation strategy was proposed to construct efficient RTP materials by in-situ deriving guest molecules and forming a rigid matrix during co-pyrolysis of guest molecules and urea. Characterizations and theoretical calculations revealed that the generated derivatives were beneficial for promoting intersystem crossing (ISC) to produce more triplet excitons, while rigid matrix could effectively suppress the non-radiative transition of triplet excitons. Thus, the in-situ derivation strategy was concluded to simultaneously promote the generation and stabilization of triplet excitons. With this method, the ultralong lifetime of RTP materials could reach up to 5.33 s and polychromatic RTP materials were easily achieved. Moreover, the potential applications of the RTP materials in reprocessing or editable anti-counterfeiting were successfully demonstrated.


Assuntos
Pirólise , Radiação , Temperatura
6.
J Chem Phys ; 158(20)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37232438

RESUMO

We develop a theory for the motion of a particle grafted with inhomogeneous bead-spring Rouse chains via the generalized Langevin equation (GLE), where individual grafted polymers are allowed to take different bead friction coefficients, spring constants, and chain lengths. An exact solution of the memory kernel K(t) is obtained for the particle in the time (t) domain in the GLE, which depends only on the relaxation of the grafted chains. The t-dependent mean square displacement g(t) of the polymer-grafted particle is then derived as a function of the friction coefficient γ0 of the bare particle and K(t). Our theory offers a direct way to quantify the contributions of the grafted chain relaxation to the mobility of the particle in terms of K(t). This powerful feature enables us to clarify the effect on g(t) of dynamical coupling between the particle and grafted chains, leading to the identification of a relaxation time of fundamental importance in polymer-grafted particles, namely, the particle relaxation time. This timescale quantifies the competition between the contributions of the solvent and grafted chains to the friction of the grafted particle and separates g(t) into the particle- and chain-dominated regimes. The monomer relaxation time and the grafted chain relaxation time further divide the chain-dominated regime of g(t) into subdiffusive and diffusive regimes. Analysis of the asymptotic behaviors of K(t) and g(t) provides a clear physical picture of the mobility of the particle in different dynamical regimes, shedding light on the complex dynamics of polymer-grafted particles.

7.
Am J Transl Res ; 15(2): 878-895, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36915728

RESUMO

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) cells often reprogram their metabolisms. Enolase 3 (ENO3) is closely related to the Warburg effect observed in cells during tumor progression. However, the expression and function of ENO3 in ccRCC cells remain unclear. Therefore, this study investigated the expression and functional significance of ENO3 in the Warburg effect observed in ccRCC cells. METHODS: In this study, B-mode and microflow imaging ultrasound examinations were performed to evaluate patients with ccRCC. The extracellular acidification rate test and glucose uptake and lactate production assays were used to examine the Warburg effect in ccRCC cells. Western blotting, quantitative reverse transcription polymerase chain reaction, and immunochemistry were used to detect the expression of ENO3 and NOP2/Sun RNA methyltransferase 5 (NSUN5). RESULTS: ENO3 upregulation in ccRCC tumor tissues was accompanied by an increase in tumor size. Importantly, ENO3 participated in the Warburg effect observed in ccRCC cells, and high levels of ENO3 indicated a poor prognosis for patients. Loss of ENO3 reduced glucose uptake, lactate production, and extracellular acidification rate as well as inhibited ccRCC cell proliferation. Furthermore, NSUN5 was involved in the ENO3-regulated Warburg effect and ccRCC cell progression. Mechanically, NSUN5 was upregulated in ccRCC tissues, and NSUN5 upregulation mediated 5-methylcytosine modification of messenger RNA (mRNA) in ccRCC cells to promote mRNA stability and ENO3 expression. CONCLUSIONS: Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.

8.
J Infect Dev Ctries ; 17(12): 1667-1673, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252719

RESUMO

INTRODUCTION: Systematic evaluation of the diagnostic value of next generation sequencing (NGS) in sepsis etiology. METHODOLOGY: We conducted a systematic search on four databases (Web of Science, Cochrane, PubMed, and Embase) and compiled diagnostic experiments using NGS to evaluate sepsis etiology. Two researchers conducted research and obtained data independently. RESULTS: Nine documents were included comprising 747 patients, 988 blood samples, 175 bronchoalveolar lavage fluid (BALF) samples, 16 cerebrospinal fluid samples, and one urine sample. The combined sensitivity of each study was 0.89 (95% CI: 0.82-0.95). The combined specificity was 0.40 (95% CI: 0.25-0.55). The combined positive likelihood ratio was 1.51 (95% CI: 1.18-1.98). The combined negative likelihood ratio was 0.28 (95% CI: 0.11-0.48). The diagnostic odds ratio (DOR) was 6.38 (95% CI: 2.53-15.32) and the area under the curve (AUC) was 0.84, (95% CI: 0.62-0.94). CONCLUSIONS: Based on the data we collected, we found that compared with the blood culture technology, NGS has the advantages of high sensitivity and wide detection range, but its specificity was low. Further study is needed to confirm the value of NGS in the etiological diagnosis of patients with sepsis.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Sepse , Humanos , Sepse/diagnóstico , Área Sob a Curva , Hemocultura , Líquido da Lavagem Broncoalveolar
9.
J Chem Phys ; 157(22): 224901, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36546812

RESUMO

The generalized Langevin equation (GLE) provides an attractive theoretical framework for investigating the dynamics of conformational fluctuations of polymeric systems. While the memory kernel is a central function in the GLE, explicit analytical forms for this function have been challenging to obtain, even for the simple models of polymer dynamics. Here, we achieve an explicit analytical expression for the memory kernel in the GLE for the end-to-end vector of Rouse chains in the overdamped limit. Our derivation takes advantage of the finding that the dynamics of the end-to-end vector of Rouse chains with both free ends are equivalent to those of Rouse chains with one free end and the other fixed. For the latter model, we first show that the equations of motion of the Rouse modes as well as their statistical properties can be obtained under the boundary conditions where the free end is held fixed temporarily. We then analytically solve the terms associated with intrachain interactions in the GLE. By formally comparing these terms with the GLE based on the Rouse modes, we obtain an explicit expression for the memory kernel, along with analytical forms for the potential field and the random colored noise force. Our analytical memory kernel is confirmed by numerical calculations in the Laplace space and is shown to yield asymptotic behaviors that are consistent with previous studies. Finally, we utilize our analytical result to simulate the cyclization dynamics of Rouse chains and discuss the scaling of the cyclization time with chain length.


Assuntos
Polímeros , Conformação Molecular , Movimento (Física)
10.
Front Oncol ; 12: 964314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276089

RESUMO

There is a need to standardize the process of micro/nanobubble preparation to bring it closer to clinical translation. We explored a neural network-based model to predict the structure-echogenicity relationship for the preparation and fabrication of ultrasound-enhanced contrast agents. Seven formulations were screened, and 109 measurements were obtained. An artificial neural network-multilayer perceptron (ANN-MLP) model was used. The original data were divided into the training and testing groups, which included 73 and 36 groups of data, respectively. The hidden layer was selected from three hidden layers and included bias. The classification graph showed that the predicted values of the training and testing groups were 76.7% and 66.7%, respectively. According to the receiver operating characteristic curve, the accuracy of different imaging effects could achieve a prediction rate of 88.1-96.5%. The percentage graph showed that the data were gradually converging. The predictive analysis curves of different ultrasound effects gradually approached stable value of Gain. Normalized importance predicted contributions for the Pk1, poly-dispersity index (PDI), and intensity account were 100%, 98.5%, and 89.7%, respectively. The application of the ANN-MLP model is feasible and effective for the exploration of the synthesis process of ultrasound contrast agents. 1,2-Distearoyl-sn-glycero-3 phosphoethanolamine-N (methoxy[polyethylene glycol]-2000) (DSPE PEG-2000) correlated highly with the success rate of contrast agent synthesis.

11.
Bioengineered ; 12(2): 10723-10733, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34752201

RESUMO

RAS p21 protein activator 4 (RASA4) has been recognized as a Ca2+-promoted Ras-MAPK pathway suppressor that inhibits tumor growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. The mRNA levels of RASA4 were analyzed using the GEO and GEPIA databases. Kaplan-Meier analysis and ROC analyses were conducted to determine the prognostic and diagnostic values for patients from the TCGA-CSCE cohort. The CCK8 and colony assays were performed to assess the impact of RASA4 ectopic expression and gene inactivation on tumor cell proliferation. In vivo experiments were performed. Luciferase reporter assays and LW6 (a HIFα inhibitor) were employed to verify the regulatory relationship between RASA4 and the HIFa signaling pathway. The GEPIA and GEO database analysis demonstrated poorly expressed RASA4 in the CESC tissues relative to that in the noncancerous tissues. Based on the TCGA database, poorly expressed RASA4 signified high prognostic and diagnostic values. Ectopically expressed RASA4 weakened the proliferative potential of HeLa cells, whereas RASA4 genetic inactivation produced the opposite impact in the HeLa and C-33A cells. The promoting effect of RASA4 deficiency on tumourigenesis was also recorded in vivo. Subsequently, RASA4 negatively regulated the HIFα-driven luciferase activities and weakened the expression of survivin. Meanwhile, LW6 treatment abrogated the increased proliferation of HeLa cells, as well as the increased expression of survivin by RASA4 depletion. Our findings indicated that RASA4 can inhibit the proliferation of cervical cancer cells by inactivating the HIFα signaling pathway, suggesting novel prospects for targeted therapy against CESC.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/genética , Proteínas Ativadoras de ras GTPase/genética , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Prognóstico , RNA Mensageiro/genética
12.
Cancer Cell Int ; 21(1): 410, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348712

RESUMO

BACKGROUND: Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. METHODS: In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. RESULTS: We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. CONCLUSIONS: Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

13.
Exp Ther Med ; 22(3): 910, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34306184

RESUMO

Cardiac ischemia-reperfusion can cause severe damage to cardiomyocytes. Previous studies have revealed that TGF-ß can alleviate ischemia-reperfusion injury in cardiomyocytes by inducing the expression of long non-coding RNA (lncRNA) activated by TGF-ß (ATB). However, M2 macrophages can secrete a large amount of TGF-ß. However, whether M2 macrophages alleviate the ischemia-reperfusion-induced injury of cardiomyocytes by secreting TGF-ß is unclear. In the present study, macrophages and cardiomyocytes were cultured under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate ischemia-reperfusion injury. M2-type macrophage markers (IL-10, Arginase-1 and IL-13) were validated using reverse transcription-quantitative PCR and western blotting. Subsequently, the culture medium of M2-type macrophages was collected for the treatment of cardiomyocytes, which were cultured under OGD/R conditions. The levels of inflammatory factors and oxidase enzymes were detected with ELISA. The apoptotic rates of cardiomyocytes were detected by flow cytometry. The expression of cell apoptosis-related proteins and the phosphorylation levels of NF-κB were analyzed by western blotting. The expression levels of specific inflammatory cytokines and the levels of malondialdehyde and lactate dehydrogenase were suppressed in cardiomyocytes following treatment with culture medium derived from M2-type macrophages, which were cultured under OGD/R conditions. Furthermore, OGD/R-induced apoptosis of cardiomyocytes was also relieved following treatment of the cells with macrophage medium. It was found that M2-type macrophages could secrete TGF-ß and that the culture medium of M2-type macrophages could activate the expression of lncRNA ATB in cardiomyocytes. TGF-ß secreted by M2 macrophages relieved the inflammatory response, oxidative stress and apoptosis of cardiomyocytes by inducing the expression of lncRNA ATB.

14.
Front Microbiol ; 12: 635227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868193

RESUMO

Functional genetic screening is an important method that has been widely used to explore the biological processes and functional annotation of genetic elements. CRISPR/Cas (Clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein) is the newest tool in the geneticist's toolbox, allowing researchers to edit a genome with unprecedented ease, accuracy, and high-throughput. Most recently, CRISPR interference (CRISPRi) has been developed as an emerging technology that exploits the catalytically inactive Cas9 (dCas9) and single-guide RNA (sgRNA) to repress sequence-specific genes. In this review, we summarized the characteristics of the CRISPRi system, such as programmable, highly efficient, and specific. Moreover, we demonstrated its applications in functional genetic screening and highlighted its potential to dissect the underlying mechanism of pathogenesis. The recent development of the CRISPRi system will provide a high-throughput, practical, and efficient tool for the discovery of functionally important genes in bacteria.

15.
J Neuroinflammation ; 18(1): 97, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879157

RESUMO

BACKGROUND: Our previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI. METHODS: Transient global cerebral ischemia was induced by the four-vessel occlusion method. Twenty-four hours before ischemia, rats were exposed to systemic hypoxia with 8% O2 for 30 min. Western blotting was used to detect the expression of MLKL and interleukin-1 type 1 receptor (IL-1R1) in CA1. Immunoprecipitation was used to assess the interactions among IL-1R1, RIP3, and phosphorylated MLKL (p-MLKL). The concentration of intracellular free calcium ion (Ca2+) was measured using Fluo-4 AM. Silencing and overexpression studies were used to study the role of p-MLKL in tGCI-induced neuronal death. RESULTS: Hypoxic preconditioning decreased the phosphorylation of MLKL both in neurons and microglia of CA1 after tGCI. The knockdown of MLKL with siRNA decreased the expression of p-MLKL and exerted neuroprotective effects after tGCI, whereas treatment with lentiviral delivery of MLKL showed opposite results. Mechanistically, hypoxic preconditioning or MLKL siRNA attenuated the RIP3-p-MLKL interaction, reduced the plasma membrane translocation of p-MLKL, and blocked Ca2+ influx after tGCI. Furthermore, hypoxic preconditioning downregulated the expression of IL-1R1 in CA1 after tGCI. Additionally, neutralizing IL-1R1 with its antagonist disrupted the interaction between IL-1R1 and the necrosome, attenuated the expression and the plasma membrane translocation of p-MLKL, thus alleviating neuronal death after tGCI. CONCLUSIONS: These data support that the inhibition of MLKL-dependent neuronal necroptosis through downregulating IL-1R1 contributes to neuroprotection of hypoxic preconditioning against tGCI.


Assuntos
Regulação para Baixo , Hipóxia/metabolismo , Ataque Isquêmico Transitório/metabolismo , Necroptose , Neuroproteção , Proteínas Quinases/metabolismo , Receptores Tipo I de Interleucina-1/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Região CA1 Hipocampal/metabolismo , Técnicas de Silenciamento de Genes , Precondicionamento Isquêmico , Masculino , Fármacos Neuroprotetores , Fosforilação , Ratos , Ratos Wistar , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
16.
J Int Med Res ; 49(2): 300060521994406, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33596694

RESUMO

We present a case of a 43-year-old man with advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombus. Initially, transcatheter arterial chemoembolization (TACE) was performed. Although alpha-fetoprotein (AFP) levels decreased, circulating tumour DNA (ctDNA) levels showed an upward trend, and abdominal magnetic resonance imaging (MRI) showed that tumours in the portal vein had increased. Based on ctDNA profiling, apatinib and anti-programmed cell death protein 1 (anti-PD-1) antibodies and were sequentially administered. Approximately three months later, intrahepatic tumours had significantly diminished and AFP and ctDNA levels had reduced. The response was sustained at the 23-month follow-up and the patient was in good health. Combination treatment of TACE, apatinib and anti-PD-1 antibodies was effective, and profiling of ctDNA fragmentation may be beneficial in the therapeutic management of patients with HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trombose , Adulto , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Terapia Combinada , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Veia Porta/diagnóstico por imagem , Resultado do Tratamento
17.
Appl Microbiol Biotechnol ; 104(4): 1707-1720, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31907574

RESUMO

Vibrio alginolyticus is an important fish pathogen causing pandemic diseases in marine animals. Small noncoding RNAs (sRNAs) are important posttranscriptional modulators of gene expression and involved in the pathogenesis of bacterial pathogens. Thus far, no cell density-dependent sRNA has been reported in V. alginolyticus. In this study, a cell density-dependent sRNA, Qrr, predicted based on the previous RNA-Seq analysis of V. alginolyticus cultured at low cell density (LCD) and high cell density (HCD), was characterized. The Qrr mutant showed significantly impaired growth and decreased swimming and swarming ability, and increased biofilm formation, extracellular polysaccharide content, serine protease production, and LD50 values during zebrafish infection in contrast to the wild-type strain. Qrr modulates the master regulators LuxR and AphA in quorum sensing (QS) pathways possibly at the posttranscriptional level by base pairing with the 5'-untranslated regions (5'-UTRs). Meanwhile, both LuxR and AphA could directly bind to the promoter of qrr to activate or repress its transcription, respectively. Moreover, our unbiased metabolic approaches revealed that Qrr modulates a large quantity of metabolic and lipidomic pathways, including amino acids, purine and pyrimidine derivatives, tricarboxylic acid cycle (TCA cycle) intermediates, and lipids. Collectively, this work contributes to a systematic understanding of regulatory roles of the cell density-dependent sRNA, Qrr, in V. alginolyticus.


Assuntos
Percepção de Quorum/genética , Pequeno RNA não Traduzido/genética , Vibrio alginolyticus/genética , Vibrio alginolyticus/metabolismo , Regiões 5' não Traduzidas , Animais , Biofilmes/crescimento & desenvolvimento , Dose Letal Mediana , Mutação , Processamento Pós-Transcricional do RNA , Vibrio alginolyticus/patogenicidade , Virulência , Peixe-Zebra
18.
Mol Med Rep ; 21(3): 1356-1364, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31894324

RESUMO

Epithelial­to­mesenchymal transition (EMT) is a major process involved in tumor progression and metastasis. Melatonin is secreted by the pineal gland and has been documented as a potential therapeutic agent for multiple tumors. However, the effects of melatonin on EMT during osteosarcoma (OA) development remain undefined. The present study explored the biological functions and effects of melatonin on EMT induced by transforming growth factor ß1 (TGF­ß1) and its underlying mechanisms in MG­63 cells. Using western­blotting and immunofluorescence, it was found that the switch in E­cadherin/N­cadherin and vimentin expression was induced by TGF­ß1, which was reversed by melatonin through the suppression of Snail and matrix metalloproteinase 9 (MMP­9), through hypoxia­inducible factor 1α (HIF­1α) inhibition. These findings demonstrated that the anticancer effects of melatonin against OA MG­63 cells is through the suppression of EMT via HIF­1α/Snail/MMP­9 signaling.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Melatonina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Osteossarcoma/patologia , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
19.
RSC Adv ; 10(18): 10689-10694, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35492935

RESUMO

A series of Fe-NC catalysts were synthesized by pyrolyzing an Fe complex and wheat flour at 500 °C. All of them were characterized and applied in the catalytic transfer hydrogenation of nitroarenes with formic acid. It was found that the catalytic activity was significantly affected by the size and distribution of Fe-based nanoparticles (NPs), which could be easily regulated by altering the Fe source. Meanwhile, more basic nitrogen sites were preserved on the catalyst so that the reaction ran smoothly without base additives. Among all catalysts, Fe-NC-FeCl2 exhibited the best catalytic performance due to smaller Fe3O4 NPs and greater N doping. Moreover, it showed excellent applicability for diverse nitroarenes. Obviously, this work demonstrates the importance of the metallic NPs' size and distribution, providing a new insight into the design of M-NC catalysts. The catalyst is economical and eco-friendly, and shows potential application value in industry.

20.
J Chem Phys ; 151(18): 184503, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31731847

RESUMO

Glass-formation is a ubiquitous phenomenon that is often observed in a broad class of materials ranging from biological matter to commonly encountered synthetic polymer, as well as metallic and inorganic glass-forming (GF) materials. Despite the many regularities in the dynamical properties of GF materials, the structural origin of the universal dynamical properties of these materials has not yet been identified. Recent simulations of coarse-grained polymeric GF liquids have indicated the coexistence of clusters of mobile and immobile particles that appear to be directly linked, respectively, to the rate of molecular diffusion and structural relaxation. The present work examines the extent to which these distinct types of "dynamic heterogeneity" (DH) arise in metallic GF liquids (Cu-Zr, Ni-Nb, and Pd-Si alloys) having a vastly different molecular structure and chemistry. We first identified mobile and immobile particles and their transient clusters and found the DH in the metallic alloys to be remarkably similar in form to polymeric GF liquids, confirming the "universality" of the DH phenomenon. Furthermore, the lifetime of the mobile particle clusters was found to be directly related to the rate of diffusion in these materials, while the lifetime of immobile particles was found to be proportional to the structural relaxation time, providing some insight into the origin of decoupling in GF liquids. An examination of particles having a locally preferred atomic packing, and clusters of such particles, suggests that there is no one-to-one relation between these populations of particles so that an understanding of the origin of DH in terms of static fluid structure remains elusive.

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