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1.
J Am Chem Soc ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32176485

RESUMO

Selective and efficient catalytic conversion of carbon dioxide (CO2) into value-added fuels and feedstocks provides an ideal avenue to high-density renewable energy storage. An impediment to enabling deep CO2 reduction to oxygenates and hydrocarbons (e.g., C2+ compounds) is the difficulty of coupling carbon-carbon bonds efficiently. Copper in the +1 oxidation state has been thought to be active for catalyzing C2+ formation, whereas it is prone to being reduced to Cu0 at cathodic potentials. Here we report that catalysts with nanocavities can confine carbon intermediates formed in situ, which in turn covers the local catalyst surface and thereby stabilizes Cu+ species. Experimental measurements on multihollow cuprous oxide catalyst exhibit a C2+ Faradaic efficiency of 75.2 ± 2.7% at a C2+ partial current density of 267 ± 13 mA cm-2 and a large C2+-to-C1 ratio of ∼7.2. Operando Raman spectra, in conjunction with X-ray absorption studies, confirm that Cu+ species in the as-designed catalyst are well retained during CO2 reduction, which leads to the marked C2+ selectivity at a large conversion rate.

2.
Chem Sci ; 11(1): 148-153, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-32110366

RESUMO

Herein, by directly introducing mismatched reactant DNA, high-reactivity and high-threshold enzyme-free target recycling amplification (EFTRA) is explored. The developed high-efficiency EFTRA (HEEFTRA) was applied as a programmable DNA signal converter, possessing higher conversion efficiency than the traditional one with perfect complement owing to the more negative reaction standard free energy (ΔG). Once traces of input target miRNA interact with the mismatched reactant DNA, amounts of ferrocene (Fc)-labeled output DNA could be converted via the EFTRA. Impressively, the Fc-labeled output DNA could be easily captured by the DNA tetrahedron nanoprobes (DTNPs) on the electrode surface to form triplex-forming oligonucleotide (TFO) at pH = 7.0 for sensitive electrochemical signal generation and the DTNPs could be regenerated at pH = 10.0, from which the conversion efficiency (N) will be accurately obtained, benefiting the selection of suitable mismatched bases to obtain high-efficiency EFTRA (HEEFTRA). As a proof of concept, the HEEFTRA as an evolved DNA signal converter is successfully applied for the ultrasensitive detection of miRNA-21, which gives impetus to the design of other signal converters with excellent efficiency for ultimate applications in sensing analysis, clinical diagnosis, and other areas.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31884699

RESUMO

A considerable challenge in the conversion of carbon dioxide into useful fuels comes from the activation of CO2 to CO2 .- or other intermediates, which often requires precious-metal catalysts, high overpotentials, and/or electrolyte additives (e.g., ionic liquids). We report a microwave heating strategy for synthesizing a transition-metal chalcogenide nanostructure that efficiently catalyzes CO2 electroreduction to carbon monoxide (CO). We found that the cadmium sulfide (CdS) nanoneedle arrays exhibit an unprecedented current density of 212 mA cm-2 with 95.5±4.0 % CO Faraday efficiency at -1.2 V versus a reversible hydrogen electrode (RHE; without iR correction). Experimental and computational studies show that the high-curvature CdS nanostructured catalyst has a pronounced proximity effect which gives rise to large electric field enhancement, which can concentrate alkali-metal cations resulting in the enhanced CO2 electroreduction efficiency.

4.
Nat Commun ; 10(1): 5338, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767845

RESUMO

Many platinum group metal-free inorganic catalysts have demonstrated high intrinsic activity for diverse important electrode reactions, but their practical use often suffers from undesirable structural degradation and hence poor stability, especially in acidic media. We report here an alkali-heating synthesis to achieve phase-mixed cobalt diselenide material with nearly homogeneous distribution of cubic and orthorhombic phases. Using water electroreduction as a model reaction, we observe that the phase-mixed cobalt diselenide reaches the current density of 10 milliamperes per square centimeter at overpotential of mere 124 millivolts in acidic electrolyte. The catalyst shows no sign of deactivation after more than 400 h of continuous operation and the polarization curve is well retained after 50,000 potential cycles. Experimental and computational investigations uncover a boosted covalency between Co and Se atoms resulting from the phase mixture, which substantially enhances the lattice robustness and thereby the material stability. The findings provide promising design strategy for long-lived catalysts in acid through crystal phase engineering.

5.
Cancer Res ; 79(23): 5930-5943, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484669

RESUMO

The genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway-associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival. SIGNIFICANCE: This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications.See related commentary by Sehgal and Barbie, p. 5915.

6.
Phys Rev Lett ; 123(9): 093001, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31524438

RESUMO

Helium (^{4}He) nanodroplets provide a unique environment to observe the microscopic origins of superfluidity. The search for another superfluid substance has been an ongoing quest in the field of quantum fluids. Nearly two decades ago, experiments on doped parahydrogen (p-H_{2}) clusters embedded in ^{4}He droplets displayed anomalous spectroscopic signatures that were interpreted as a sign of the superfluidity of p-H_{2} [S. Grebenev et al., Science 289, 1532 (2000)SCIEAS0036-807510.1126/science.289.5484.1532]. Here, we observe, using first-principles quantum Monte Carlo simulations, a phase separation between a symmetric and localized p-H_{2} core and ^{4}He shells. The p-H_{2} core has minimal superfluid response. These findings are consistent with the recorded spectra but not with their original interpretation, and lead us to conclude that doped p-H_{2} clusters form a nonsuperfluid core in ^{4}He droplets.

7.
Eur J Cancer ; 119: 87-96, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31425966

RESUMO

BACKGROUND: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. PATIENTS AND METHODS: Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population). RESULTS: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval [CI] 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% [39/238] versus 9.7% [23/238], p = 0.029). CONCLUSION: IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.

8.
J Chem Phys ; 151(7): 074301, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438702

RESUMO

The rovibrational energy levels and intensities of the CH3F-H2 dimer have been obtained using our recent global intermolecular potential energy surface [X.-L. Zhang et al., J. Chem. Phys. 148, 124302 (2018)]. The Hamiltonian, basis set, and matrix elements are derived and given for a symmetric top-linear molecule complex. This approach to the generation of energy levels and wavefunctions can readily be utilized for studying the rovibrational spectra of other van der Waals complexes composed of a symmetric top molecule and a linear molecule, and may readily be extended to other complexes of nonlinear molecules and linear molecules. To confirm our method, the rovibrational levels of the H2O-H2 dimer have been computed and shown to be in good agreement with experiment and with previous theoretical results. The rovibrational Schrödinger equation has been solved using a Lanczos algorithm together with an uncoupled product basis set. As expected, dimers containing ortho-H2 are more strongly bound than dimers containing para-H2. Energies and wavefunctions of the discrete rovibrational levels of CH3F-paraH2 complexes obtained from the direct vibrationally averaged 5-dimensional potentials are in good agreement with the results of the reduced 3-dimensional adiabatic-hindered-rotor (AHR) approximation. Accurate calculations of the transition line strengths for the orthoCH3F-paraH2 complex are also carried out, and are consistent with results obtained using the AHR approximation. The microwave spectrum associated with the orthoCH3F-orthoH2 dimer has been predicted for the first time.

9.
iScience ; 19: 623-633, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31446225

RESUMO

It is well known that nuclear factor-kappaB (NF-κB) regulates neuronal structures and functions by nuclear transcription. Here, we showed that phospho-p65 (p-p65), an active form of NF-κB subunit, reversibly interacted with Nav1.7 channels in the membrane of dorsal root ganglion (DRG) neurons of rats. The interaction increased Nav1.7 currents by slowing inactivation of Nav1.7 channels and facilitating their recovery from inactivation, which may increase the resting state of the channels ready for activation. In cultured DRG neurons TNF-α upregulated the membrane p-p65 and enhanced Nav1.7 currents within 5 min but did not affect nuclear NF-κB within 40 min. This non-transcriptional effect on Nav1.7 may underlie a rapid regulation of the sensibility of the somatosensory system. Both NF-κB and Nav1.7 channels are critically implicated in many physiological functions and diseases. Our finding may shed new light on the investigation into the underlying mechanisms.

10.
Front Plant Sci ; 10: 665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191579

RESUMO

Phosphorus (P) starvation leads to increased reutilization of cell wall P in rice (Oryza sativa). Carbon dioxide (CO2) is involved not only in plant growth and development but also in the response to abiotic stresses. However, it remains unclear whether CO2 affects the reutilization of cell wall P in rice when subjected to P deficiency. In the present study, elevated CO2 (600 µl·L-1) significantly increased the soluble P content in shoots when compared with ambient CO2 (400 µl·L-1). This positive effect was accompanied by an increase of pectin content, as well as an increase of pectin methylesterase (PME) activity, which results in P release from the shoot cell wall, making it available for plant growth. P deficiency significantly induced the expression of phosphate transporter genes (OsPT2, OsPT6, and OsPT8) and decreased the P content in the xylem sap, but elevated CO2 had no further effect, indicating that the increased soluble P content observed in shoots under elevated CO2 is attributable to the reutilization of shoot cell wall P. Elevated CO2 further increased the P deficiency-induced ethylene production in the shoots, and the addition of the ethylene precursor 1-amino-cyclopropane-1-carboxylic acid (ACC) mimicked this effect, while the addition of the ethylene inhibitor aminoethoxyvinylglycine (AVG) abolished this effect. These results further support the role of ethylene in the alleviation of P deficiency under elevated CO2. Taken together, our results indicate that the improvement of P nutrition in rice by elevated CO2 is mediated by increasing the shoot cell wall pectin content and PME activity, possibly via the ethylene signaling pathway.

12.
Nanomaterials (Basel) ; 9(4)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974787

RESUMO

Graphene has attracted attention in the material field of functional microcapsules because of its excellent characteristics. The content and state of graphene in shells are critical for the properties of microcapsules, which are greatly affected by the charge adsorption equilibrium. The aim of this work was to investigate the effect of pH value on the microstructure and properties of self-assembly graphene microcapsules in regard to chemical engineering. Microcapsule samples were prepared containing liquid paraffin by a self-assembly polymerization method with graphene/organic hybrid shells. The morphology, average size and shell thickness parameters were investigated for five microcapsule samples fabricated under pH values of 3, 4, 5, 6 and 7. The existence and state of graphene in dry microcapsule samples were analyzed by using methods of scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). Fourier Transform Infrared Spectoscopy (FT-IR) and Energy Dispersive Spectrometer (EDS) were applied to analyze the graphene content in shells. These results proved that graphene had existed in shells and the pH values greatly influenced the graphene deposition on shells. It was found that the microcapsule sample fabricated under pH = 5 experienced the largest graphene deposited on shells with the help of macromolecules entanglement and electrostatic adherence. This microcapsules sample had enhanced thermal stability and larger thermal conductivity because of additional graphene in shells. Nanoindentation tests showed this sample had the capability of deforming resistance under pressure coming from the composite structure of graphene/polymer structure. Moreover, more graphene decreased the penetrability of core material out of microcapsule shells.

13.
J Am Chem Soc ; 141(18): 7537-7543, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017425

RESUMO

The design of highly efficient non-noble-metal electrocatalysts for large-scale hydrogen production remains an ongoing challenge. We report here a Ni2P nanoarray catalyst grown on a commercial Ni foam substrate, which demonstrates an outstanding electrocatalytic activity and stability in basic electrolyte. The high catalytic activity can be attributed to the favorable electron transfer, superior intrinsic activity, and the intimate connection between the nanoarrays and their substrate. Moreover, the unique "superaerophobic" surface feature of the Ni2P nanoarrays enables a remarkable capability to withstand internal and external forces and release the in situ generated H2 bubbles in a timely manner at large current densities (such as >1000 mA cm-2) where the hydrogen evolution becomes vigorous. Our results highlight that an aerophobic structure is essential to catalyze gas evolution for large-scale practical applications.

14.
Biotechnol Appl Biochem ; 66(3): 389-397, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30715749

RESUMO

The high cell density culture of baker's yeast FX-2 was investigated in a 50 L(A) automatic bioreactor. Herein, it was found firstly that the Crabtree effect clearly existed in batch fermentation with higher glucose content, then the critical initial glucose content range (≤2.00 g L-1 ) was reasonably ascertained to effectively avoid Crabtree effect. In the next fed-batch fermentations with different strategies, the second strategy (maintain ethanol concentration lower than 0.10% and pH around 4.80) was confirmed to be more beneficial to yeast growth than the first strategy (keep reducing sugar not more than 2.00 g L-1 and control steady Carbon/Nitrogen ratio 3.05:1.00). After that, one optimal control strategy (maintain pH around 4.80 and keep respiratory quotient in the range of 0.90-1.00) was constructed to further enhance cell yield. Under an optimal control strategy, four schemes with the aim of achieving pH-stat were compared, and yeast extract instead of other alkaline materials was selected as a better regulator. As a result, 148.37 g L-1 dry cell weight, 38.25 × 108 mL-1 living cells, and 8.24 g L-1  h-1 productivity were harvested, which respectively elevated 23.74%, 135.38%, and 24.47% compared to that obtained under the traditional scheme (regulate pH with ammonia); meanwhile, the maximum oxygen uptake rate and carbon dioxide excretion rate were both more than 250.00 mmol L-1  min-1 .


Assuntos
Técnicas de Cultura de Células , Fermentação , Saccharomyces cerevisiae/citologia , Reatores Biológicos , Glucose/química , Glucose/metabolismo , Concentração de Íons de Hidrogênio , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Fatores de Tempo
15.
Neural Netw ; 112: 1-14, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30716617

RESUMO

Images are often represented as vectors with high dimensions when involved in classification. As a result, dimensionality reduction methods have to be developed to avoid the curse of dimensionality. Among them, Laplacian eigenmaps (LE) have attracted widespread concentrations. In the original LE, point to point (P2P) distance metric is often adopted for manifold learning. Unfortunately, they show few impacts on robustness to noises. In this paper, a novel supervised dimensionality reduction method, named feature space to feature space distance metric learning (FSDML), is presented. For any point, it can construct a feature space spanned by its k intra-class nearest neighbors, which results in a local projection on its nearest feature space. Thus feature space to feature space (S2S) distance metric will be defined to Euclidean distance between two corresponding projections. On one hand, the proposed S2S distance metric displays superiority on robustness by the local projection. On the other hand, the projection on the nearest feature space contributes to fully mining local geometry information hidden in the original data. Moreover, both class label similarity and dissimilarity are also measured, based on which an intra-class graph and an inter-class graph will be individually modeled. Finally, a subspace can be found for classification by maximizing S2S based manifold to manifold distance and preserving S2S based locality of manifolds, simultaneously. Compared to some state-of-art dimensionality reduction methods, experiments validate the proposed method's performance either on synthesized data sets or on benchmark data sets.


Assuntos
Algoritmos , Aprendizagem , Análise por Conglomerados
16.
Phytomedicine ; 53: 263-273, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668406

RESUMO

BACKGROUND: Sedum sarmentosum, which is recorded in Chinese Pharmacopoeia, has been applied clinically to treat liver and gallbladder diseases. PURPOSE: This study aimed to explore the hepatoprotective effect of S. sarmentosum less polar extract (SSE) against ANIT-induced liver injury in rats, and the protective activity and mechanism of one major constituent isolated from this extract on D-GalN-induced human hepatic QSG7701 cell damage. METHODS: Rats were divided into groups and then administrated intragastrically with SSE at doses of 100, 200 and 400 mg/kg for 7 days. They were modeled in the experiments with ANIT (70 mg/kg) to induce liver injury after the sixth day administration. The levels of serum biochemical markers ALT, AST, ALP, GGT/γ-GT, DBiL, TBiL, ALB, TP, and bile flow rate, as well as the histopathology of the liver tissue were used as indices of liver damage and measured. The inflammatory response and oxidative stress were thought to be key contributors to ANIT-induced liver injury in rats. Therefore, the inflammatory mediators (TNF-α, IFN-γ, IL-4) and oxidative stress (ROS, SOD, GSH-PX) were measured in the serum and liver homogenates, respectively. Next, phytochemical research was performed to produce the main component, and the isolated compound was evaluated for its hepatoprotective activity against QSG7701 cell injured by D-GalN through the measurement of cell viabilities, ALT, AST, IL-1ß, TNF-α, IL-6, ROS, GSH-PX and SOD productions. Furthermore, the protein expression of the Nrf2 and NF-κB pathways were analyzed by western blotting. RESULTS: SSE had an obvious effect on the decreases of ALT, AST, ALP, GGT/γ-GT, DBiL and TBiL levels, the increases of ALB and TP levels in serum, and the ANIT-induced deceleration in bile flow for liver injury. Meanwhile, SSE pretreatment alleviated ANIT-induced liver pathological injuries exhibited by HE stain of the liver. Moreover, SSE significantly suppressed levels of pro-inflammatory cytokines TNF-α and IFN-γ, and elevated level of anti-inflammatory cytokine IL-4 in serum. SSE also attenuated oxidative stress by reducing ROS level and by enhancing antioxidative enzymes (SOD and GSH-PX) activities after ANIT administration in liver tissue. Further, the major compound shown in HPLC was isolated from SSE. Its structure was identified by the spectroscopic data analysis and comparison with literature values. The principal constituent had potent protective effect on D-GalN-induced QSG7701 cells damage in a dose dependent manner with survival rates of 58.2% and 69.5% at 10 µM and 20 µM, respectively. Its cytoprotective effect was associated with the reduction of ALT, AST, IL-1ß, TNF-α, IL-6 and ROS levels, and the elevation of GSH-PX and SOD productions in QSG7701 cells induced by D-GalN. Western blotting showed that this compound enhanced the expression of Nrf2, HO1, NQO1 and GCLC, and inhibited D-GalN-induced IκBα and NF-κB p65 phosphorylation. CONCLUSIONS: Current study showed that SSE treatment exerted a protective effect on ANIT-induced liver injury. The main compound δ-amyrone isolated from the extract was characterized as the effective component with hepatoprotective activity by promoting Nrf2 antioxidant defense and suppressing NF-κB inflammatory response.


Assuntos
Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Sedum/química , Triterpenos/farmacologia , 1-Naftilisotiocianato/toxicidade , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Substâncias Protetoras/química , Ratos Sprague-Dawley , Triterpenos/isolamento & purificação
17.
J Ultrasound Med ; 38(10): 2601-2608, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30697787

RESUMO

OBJECTIVES: To retrospectively evaluate the value of contrast-enhanced ultrasound (CEUS) perfusion parameters in the differential diagnosis of hepatocellular carcinomas (HCCs) and metastatic liver tumors (MLTs) with hypervascularity. METHODS: Sixty-seven HCCs and 55 MLTs with arterial homogeneous/heterogeneous hyperenhancement on CEUS imaging and a normal liver background were included in this retrospective study. Six CEUS perfusion parameters were compared between HCCs and MLTs with different sizes and HCC differentiations: rise time (RT), time to peak (TTP), mean transit time, wash-out time (WT), maximum intensity (IMAX), and area under the curve (AUC). The area under the receiver operating characteristic curve (AUROC) was determined to compare the diagnostic efficacy of the parameters. RESULTS: The RT, TTP, and WT were significant longer and the IMAX and AUC were significantly higher in HCCs than in MLTs. In distinguishing between HCCs and MLTs, the AUROC was highest for the WT (0.922; sensitivity, 85.1%; specificity, 89.6%); the AUC and IMAX had the second and third highest AUROCs (AUC: 0.855; sensitivity, 76.1%; specificity, 80.6%; IMAX: 0.827; sensitivity, 76.1%; specificity, 77.6%). The AUROC was lowest for the TTP and RT (TTP: 0.719; sensitivity, 70.1%; specificity, 61.2%; RT: 0.707; sensitivity, 67.2%; specificity, 65.7%). In HCCs, both the tumor size and degree of differentiation affected the IMAX, AUC, and WT. In MLTs, perfusion parameters were not influenced by the tumor size. CONCLUSIONS: In HCCs and MLTs with hypervascularity and a normal liver background on CEUS imaging, various CEUS perfusion parameters, including IMAX, AUC, WT, RT, and TTP, differed significantly between tumor types. The WT may be the most useful parameter for differentiating between these tumors.

18.
Redox Biol ; 21: 101112, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30685709

RESUMO

Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema.


Assuntos
Astrócitos/metabolismo , Edema Encefálico/metabolismo , Ácido Glutâmico/metabolismo , Íons/metabolismo , Pressão Osmótica , Proteínas/metabolismo , Animais , Biomarcadores , Linhagem Celular , Humanos , Imuno-Histoquímica , Espaço Intracelular/metabolismo , Modelos Biológicos , Nanopartículas , Ratos , Estresse Fisiológico
19.
Clin Exp Med ; 19(1): 93-104, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30361846

RESUMO

This study analysed the biological significance of TLT-2 on CD8+T cells in hepatitis B patients and provided a theoretical basis for the potential role of TLT-2 as an immune regulator. Flow cytometry sorting, isobaric tags for relative and absolute quantitation and short hairpin RNAs were used to analyse the function of TLT-2 on CD8+T cells in hepatitis B patients. The TLT-2 expression levels in the acute hepatitis B and chronic hepatitis B groups were significantly higher than that in the healthy control group and were positively correlated with ALT and AST. The CD8+TLT-2+T cells exhibited stronger immune function and greater cell proliferation ability and secreted higher levels of cytokines than the CD8+TLT-2-T cells. An analysis of the proteome differences between the TLT-2+CD8+T and TLT-2-CD8+T cells revealed that TLT-2 affected CD8+T cell activation by regulating Granzyme B expression and by further action on the NF-κB signalling pathway. This study first elucidated the mechanism by which TLT-2 influences the activation of CD8+T cells, improved the understanding of the TLT-2 signalling pathway and clarified the role of the TLT-2+CD8+T cell subset in hepatitis B virus infection. The study proposed a novel subset of CD8+T cells that could be useful for understanding the immune function of patients with hepatitis B and further elucidating the pathogenesis of hepatitis B by analysing changes in this subpopulation with the goal of providing a new target for the treatment of hepatitis B.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Hepatite B/patologia , Ativação Linfocitária , Receptores Imunológicos/análise , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Linfócitos T CD8-Positivos/química , Proliferação de Células , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma/análise
20.
Cell Mol Neurobiol ; 39(2): 241-254, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30554401

RESUMO

Retinoic acid-induced 14 is a developmentally regulated gene induced by retinoic acid and is closely associated with NIK/NF-κB signaling. In the present study, we examined the effect of RAI14 on mTOR-mediated glial inflammation in response to inflammatory factors and chemical ischemia. A U87 cell model of LPS- and TNF-α-induced inflammation was used to investigate the role of RAI14 in glial inflammation. U87 cells were treated with siR-RAI14 or everolimus to detect the correlation between mTOR, RAI14, and NF-κB. CoCl2-stimulated U87 cells were used to analyze the effect of RAI14 on mTOR-mediated NF-κB inflammatory signaling under chemical hypoxia. LPS and TNF-α stimulation resulted in the upregulation of RAI14 mRNA and protein levels in a dose- and time-dependent manner. RAI14 knockdown significantly attenuated the level of pro-inflammatory cytokine via inhibiting the IKK/NF-κB pathway. Treatment with an mTOR inhibitor (everolimus) ameliorated NF-κB activity and IKKα/ß phosphorylation via RAI14 signaling. Notably, RAI14 also enhanced mTOR-mediated NF-κB activation under conditions of chemical hypoxia. These findings provide significant insight into the role of RAI14 in mTOR-induced glial inflammation, which is closely associated with infection and ischemia stimuli. Thus, RAI14 may be a potential drug target for the treatment of inflammatory diseases.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Inflamação/metabolismo , Inflamação/patologia , Estresse Fisiológico , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Proteínas do Citoesqueleto/genética , Everolimo/farmacologia , Técnicas de Silenciamento de Genes , Glioblastoma/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Fatores de Transcrição/genética , Transcrição Genética/efeitos dos fármacos
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