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1.
Mol Cell ; 82(7): 1278-1287.e5, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35271814

RESUMO

Cholesterol molecules specifically bind to the resting αßTCR to inhibit cytoplasmic CD3ζ ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms of cholesterol-mediated inhibition of TCR-CD3 and its activation remain unclear. Here, we present cryoelectron microscopy structures of cholesterol- and cholesterol sulfate (CS)-inhibited TCR-CD3 complexes and an auto-active TCR-CD3 variant. The structures reveal that cholesterol molecules act like a latch to lock CD3ζ into an inactive conformation in the membrane. Mutations impairing binding of cholesterol molecules to the tunnel result in the movement of the proximal C terminus of the CD3ζ transmembrane helix, thereby activating the TCR-CD3 complex in human cells. Together, our data reveal the structural basis of TCR inhibition by cholesterol, illustrate how the cholesterol-binding tunnel is allosterically coupled to TCR triggering, and lay a foundation for the development of immunotherapies through directly targeting the TCR-CD3 complex.


Assuntos
Complexo Receptor-CD3 de Antígeno de Linfócitos T , Linfócitos T , Complexo CD3/genética , Complexo CD3/metabolismo , Colesterol/metabolismo , Microscopia Crioeletrônica , Humanos , Complexo Receptor-CD3 de Antígeno de Linfócitos T/genética , Complexo Receptor-CD3 de Antígeno de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo
2.
Sensors (Basel) ; 24(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38475169

RESUMO

In recent years, the application of deep learning models for underwater target recognition has become a popular trend. Most of these are pure 1D models used for processing time-domain signals or pure 2D models used for processing time-frequency spectra. In this paper, a recent temporal 2D modeling method is introduced into the construction of ship radiation noise classification models, combining 1D and 2D. This method is based on the periodic characteristics of time-domain signals, shaping them into 2D signals and discovering long-term correlations between sampling points through 2D convolution to compensate for the limitations of 1D convolution. Integrating this method with the current state-of-the-art model structure and using samples from the Deepship database for network training and testing, it was found that this method could further improve the accuracy (0.9%) and reduce the parameter count (30%), providing a new option for model construction and optimization. Meanwhile, the effectiveness of training models using time-domain signals or time-frequency representations has been compared, finding that the model based on time-domain signals is more sensitive and has a smaller storage footprint (reduced to 30%), whereas the model based on time-frequency representation can achieve higher accuracy (1-2%).

3.
Faraday Discuss ; 243(0): 55-64, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37010013

RESUMO

Noble metal elements are focal catalytic candidates for many chemical processes, but have received little attention in the field of nitrogen fixation except ruthenium and osmium. Iridium (Ir), as a representative, has been shown to be catalytically inactive for ammonia synthesis because of its weak nitrogen adsorption and severe competitive adsorption of H over N that strongly inhibits the activation of N2 molecules. Here we show that, upon compositing with lithium hydride (LiH), iridium can catalyze ammonia formation at much enhanced reaction rates. The catalytic performance of the LiH-Ir composite can be further improved by dispersion on a MgO support with a high specific surface area. At 400 °C and 10 bar, the MgO-supported LiH-Ir (LiH-Ir/MgO) catalyst shows a ca. 100-fold increase in activity compared to the bulk LiH-Ir composite and the MgO-supported Ir metal catalyst (Ir/MgO). The formation of a lithium-iridium complex hydride phase was identified and characterized, and this phase may be responsible for the activation and hydrogenation of N2 to NH3.

4.
Faraday Discuss ; 243(0): 27-37, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37013703

RESUMO

Nickel (Ni) metal has long been considered to be far less active for catalytic ammonia synthesis as compared to iron, cobalt, and ruthenium. Herein, we show that Ni metal synergized with barium hydride (BaH2) can catalyse ammonia synthesis with an activity comparable to that of an active Cs-Ru/MgO catalyst typically below 300 °C. Kinetic analyses show that the addition of BaH2 makes the apparent activation energy for the Ni catalyst decrease dramatically from 150 kJ mol-1 to 87 kJ mol-1. This result together with N2-TPR experiments suggests a strong synergistic effect between Ni and BaH2 for promoting N2 activation and hydrogenation to NH3. It is suggested that an intermediate [N-H] species is generated upon N2 fixation and then is hydrogenated to NH3 with the regeneration of hydride species, forming a catalytic cycle.

5.
Neurol Neurochir Pol ; 57(2): 160-168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36580081

RESUMO

OBJECTIVE: To explore the efficacy of multi-layer skull base reconstruction after endoscopic transnasal surgery for invasive pituitary adenomas (IPAs). CLINICAL RATIONALE FOR THE STUDY: Skull base reconstruction for IPAs. MATERIAL AND METHODS: This retrospective analysis involved 160 patients with IPAs who underwent operations from October 2018 to October 2020. All patients were diagnosed with IPAs by pituitary enhanced magnetic resonance imaging, and all tumours were confirmed to be Knosp grades 3a, 3b, or 4. The experimental group and the control group comprised 80 patients in each, and we used different methods to reconstruct the skull base in each group. The comparison indicators included cerebrospinal fluid leakage, sellar floor bone flap (or middle turbinate) shifting, delayed healing of the skull base reconstructed tissue, nasal discomfort, and epistaxis. We used the chi-square test, and p < 0.05 was considered statistically significant. RESULTS: In the experimental group, cerebrospinal fluid leakage occurred intraoperatively in 73 patients, two of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed no sellar floor bone flap (or middle turbinate) shifting. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 74 patients and had failed to heal in six. However, endoscopic transnasal checks showed that all six of these patients' pedicled nasoseptal flaps had healed well by 14 days after surgery. Other sequelae comprised nasal discomfort in four patients, and epistaxis in four. In the control group, cerebrospinal fluid leakage occurred intraoperatively in 71 patients, 14 of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed floor bone flap (or middle turbinate) shifting in 12 patients. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 65 patients. In 12 patients, pedicled nasoseptal flaps had healed well by 14 days after surgery, while the remaining three patients required reoperation. Other sequelae comprised nasal discomfort in five patients, and epistaxis in six. CONCLUSIONS: This new method of multi-layer skull base reconstruction could play an important role in endoscopic transnasal IPA surgery.


Assuntos
Adenoma , Neoplasias Hipofisárias , Procedimentos de Cirurgia Plástica , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Epistaxe/cirurgia , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Endoscopia/métodos , Vazamento de Líquido Cefalorraquidiano/etiologia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Septo Nasal/cirurgia
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 699-704, 2023 May.
Artigo em Zh | MEDLINE | ID: mdl-37248608

RESUMO

Thoracic aortic dissection (TAD) is a cardiovascular disease entailing a high lethality between 65% and 85%. Surgery-assissed implant/interventional stenting is the prevailing treatment of TAD. However, surgical treatment can cause severe postoperative complications and patients incur a relatively higher risk of postoperative mortality. Since the pathogenic mechanism underlying TAD is not clear, effective medication therapies are still not available. In recent years, along with advances in single-cell sequencing and other molecular biological technologies, there have been prelimiary findings suggesting the special role of dysfunctional vascular smooth muscle cells (VSMCs) in the pathogenesis and development of TAD. Furthermore, the molecular mechanisms regulating the dysfunction of VSMCs have been initially explored. It is expected that these new findings will contribute to the development of new strategies to prevent TAD and lead to new ideas for the identifiction of potential drug therapeutic targets. Herein, we summarized the critical role of dysfunctional VSMCs in the pathogenesis and development of TAD and presented in detail the biological factors and the related molecular mechanisms that regulate the dysfunction of VSMCs. We hope this review will provide a reference for further investigation into the central role of dysfunctional VSMCs in the pathogenesis and development of TAD and exploration for effective molecular drug targets for TAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Dissecção da Aorta Torácica , Humanos , Aneurisma da Aorta Torácica/patologia , Aorta Torácica/patologia
7.
Int J Mol Sci ; 23(24)2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36555344

RESUMO

Fluid shear stress (FSS) facilitates bone remodeling by regulating osteogenic differentiation, and extracellular matrix maturation and mineralization. However, the underlying molecular mechanisms of how mechanical stimuli from FSS are converted into osteogenesis remain largely unexplored. Here, we exposed MC3T3-E1 cells to FSS with different intensities (1 h FSS with 0, 5, 10, and 20 dyn/cm2 intensities) and treatment durations (10 dyn/cm2 FSS with 0, 0.5, 1, 2 and 4 h treatment). The results demonstrate that the 1 h of 10 dyn/cm2 FSS treatment greatly upregulated the expression of osteogenic markers (Runx2, ALP, Col I), accompanied by AnxA6 activation. The genetic ablation of AnxA6 suppressed the autophagic process, demonstrating lowered autophagy markers (Beclin1, ATG5, ATG7, LC3) and decreased autophagosome formation, and strongly reduced osteogenic differentiation induced by FSS. Furthermore, the addition of autophagic activator rapamycin to AnxA6 knockdown cells stimulated autophagy process, and coincided with more expressions of osteogenic proteins ALP and Col I under both static and FSS conditions. In conclusion, the findings in this study reveal a hitherto unidentified relationship between FSS-induced osteogenic differentiation and autophagy, and point to AnxA6 as a key mediator of autophagy in response to FSS, which may provide a new target for the treatment of osteoporosis and other diseases.


Assuntos
Proteínas Morfogenéticas Ósseas , Osteogênese , Osteogênese/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Autofagia , Osteoblastos
8.
Angew Chem Int Ed Engl ; 61(39): e202205805, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-35918291

RESUMO

Transition-metal-mediated dinitrogen fixation has been intensively investigated. The employment of main group elements for this vital reaction has recently sparked interest because of new dinitrogen reaction chemistry. We report ammonia synthesis via a chemical looping process mediated by a transition-metal-free barium hydride (BaH2 ). Experimental and computational studies reveal that the introduction of hydrogen vacancies is essential for creating multiple coordinatively unsaturated Ba sites for N2 activation. The adjacent lattice hydridic hydrogen (H- ) then undergoes both reductive elimination and reductive protonation to convert N2 to NHx . The ammonia production rate supports this hydride-vacancy mechanism via a chemical looping route that far exceeds that of a catalytic process. The BaH2 -mediated chemical looping process has prospects in future technologies for ammonia synthesis using transition-metal-free materials.

9.
J Am Chem Soc ; 143(49): 20891-20897, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34854674

RESUMO

Selective hydrogenation of alkynes to alkenes requires a catalytic site with suitable electronic properties for modulating the adsorption and conversion of alkyne, alkene as well as dihydrogen. Here, we report a complex palladium hydride, CaPdH2, featured by electron-rich [PdH2]δ- sites that are surrounded by Ca cations that interacts with C2H2 and C2H4 via σ-bonding to Pd and unusual cation-π interaction with Ca, resulting in a much weaker chemisorption than those of Pd metal catalysts. Concomitantly, the dissociation of H2 and hydrogenation of C2Hx (x = 2-4) species experience significant energy barriers over CaPdH2, which is fundamentally different from those reported Pd-based catalysts. Such a unique catalytic environment enables CaPdH2, the very first complex transition-metal hydride catalyst, to afford a high alkene selectivity for the semihydrogenation of alkynes.

10.
Mol Carcinog ; 60(9): 607-619, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107107

RESUMO

Hepatocellular carcinoma is a highly fatal disease and threatens human health seriously. Fluid shear stress (FSS), which is caused by the leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage, has been identified as contributing pathologically to cancer metastasis. Autophagy and epithelial-mesenchymal transition (EMT) are both reported to be involved in cancer cell migration and invasion, but little has been revealed about the interaction between autophagy and EMT under a tumor mechanical microenvironment. Here, we identified that exposure to 1.4 dyne/cm2 FSS could promote the formation of autophagosomes and significantly increase the expressions of autophagy-related markers of beclin1 and ATG7, and the ratio of LC3Ⅱ/Ⅰ in both of HepG2 and QGY-7703 cells. The FSS loading also elevated the levels of mesenchymal markers N-cadherin, Vimentin, Twist, Snail, and ß-catenin, while the epithelial markers E-cadherin showed a decrease. Once the autophagy was blocked by 3-methyladenine (3-MA) or knocking ATG5 down, the occurrence of FSS-induced EMT was inhibited dramatically according to the expression and translocation of E-cadherin, N-cadherin, and ß-catenin. Given the effect of EMT on cell migration, we observed that inhibition of autophagy could impede FSS-induced cell migration. Collectively, this study demonstrated that autophagy played a crucial role in FSS-induced EMT and cell migration in hepatocellular carcinoma.


Assuntos
Autofagia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Resistência ao Cisalhamento , Autofagossomos/metabolismo , Autofagia/genética , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular , Suscetibilidade a Doenças , Humanos , Microambiente Tumoral
11.
Pharmacol Res ; 172: 105843, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34428586

RESUMO

SUMOylation of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) has been shown to play a critical role in the abnormal Ca2+ cycle of heart failure. Ginsenoside Rg3 (Rg3), the main active constituent of Panax ginseng, exerts a wide range of pharmacological effects in cardiovascular diseases. However, the effect of Rg3 on abnormal Ca2+ homeostasis in heart failure has not been reported. In this study, we showed a novel role of Rg3 in the abnormal Ca2+ cycle in cardiomyocytes of mice with heart failure. Among mice undergoing transverse aortic constriction, animals that received Rg3 showed improvements in cardiac function and Ca2+ homeostasis, accompanied by increases in the SUMOylation level and SERCA2a activity. In an isoproterenol (ISO)-induced cell hypertrophy model, Rg3 reduced the ISO-induced Ca2+ overload in HL-1 cells. Gene knockout of SUMO1 in mice inhibited the cardioprotective effect of Rg3, and SUMO1 knockout mice that received Rg3 did not exhibit improved Ca2+ homeostasis in cardiomyocytes. Additionally, mutation of the SUMOylation sites of SERCA2a blocked the positive effect of Rg3 on the ISO-induced abnormal Ca2+ cycle in HL-1 cells, and was accompanied by an abnormal endoplasmic reticulum stress response and generation of ROS. Our data demonstrated that Rg3 has a positive effect on the abnormal Ca2+ cycle in the cardiomyocytes of mice with heart failure. SUMO1 is an important factor that mediates the protective effect of Rg3. Our findings suggest that drug intervention by regulating the SUMOylation of SERCA2a can provide a novel therapeutic strategy for the treatment of heart failure.


Assuntos
Cardiotônicos/uso terapêutico , Ginsenosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sumoilação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Linhagem Celular , Ginsenosídeos/farmacologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
12.
J Craniofac Surg ; 32(5): e470-e472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33741873

RESUMO

ABSTRACT: Aneurysms of the anterior inferior cerebellar artery (AICA) are a rare entity. Purely intrameatal aneurysms are even rarer. The author reported 2 ruptured intrameatal aneurysms that were treated by fully endoscope-controlled clipping. Retrosigmoid craniotomy was performed and the aneurysm was clipped definitely intraoperative without postoperative deficits except hearing loss and slight facial nerve paresis. Follow-up angiography demonstrated exclusion of the aneurysm, confirming preservation of the distal aneurysms of the anterior inferior cerebellar artery. Endoscopic enhancement of the visual field provided by the endoscope may be a safe and effective application to increase the quality of treatment for intrameatal aneurysm, especially for deep aneurysm.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Idoso , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Artéria Basilar , Cerebelo/cirurgia , Endoscópios , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Pessoa de Meia-Idade
13.
J Craniofac Surg ; 32(2): e191-e195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705071

RESUMO

OBJECTIVE: To explore the clinical effect of sellar floor bone flap with a pedicled nasoseptal flap in endoscopic transnasal pituitary adenoma surgery for skull base reconstruction.Method: This was a retrospective clinical analysis of 30 patients with pituitary adenoma operated by the same neurosurgical team from June 2015 to June 2018. All patients were diagnosed with pituitary adenoma by pituitary magnetic resonance imaging, and the authors confirmed that the sellar floor bone was intact using sphenoid sinus computed tomography. All patients underwent an endoscopic transnasal approach, and the authors created a pedicled nasoseptal flap and sellar floor bone flap intraoperatively and reconstructed the skull base at the end of the surgery. Postoperative complications constituted cerebrospinal fluid leakage, brain tissue herniation, nasal discomfort, decreased sense of smell, and epistaxis. RESULTS: Cerebrospinal fluid leakage occurred in 13 patients (43.3%) intraoperatively; small amounts in 6 patients (20.0%), moderate amounts in 3 patients (10.0%), and large amounts in 4 patients (13.3%). Only 1 patient (3.3%) with large-volume cerebrospinal fluid leakage intraoperatively experienced cerebrospinal fluid leakage postoperatively, and this resolved with lumbar catheter drainage and bed rest. The 6-month postoperative follow-up brain computed tomography findings revealed brain tissue herniation in no patients, nasal discomfort in 3 patients (10.0%), decreased sense of smell in 5 patients (16.7%), and epistaxis in 2 patients (6.7%). CONCLUSION: Reconstructing the skull base with a sellar floor bone flap and a pedicled nasoseptal flap played an important role in preventing cerebrospinal fluid leakage and brain tissue herniation in endoscopic transnasal pituitary adenoma surgery and did not increase the incidence of postoperative nasal discomfort, decreased sense of smell, or epistaxis.


Assuntos
Neoplasias Hipofisárias , Procedimentos de Cirurgia Plástica , Vazamento de Líquido Cefalorraquidiano/cirurgia , Humanos , Septo Nasal/cirurgia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Base do Crânio/cirurgia , Retalhos Cirúrgicos
14.
J Craniofac Surg ; 31(1): e27-e30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31449206

RESUMO

OBJECTIVE: Basal ganglia hemorrhage can damage the internal capsule and lead to high rates of disability and mortality. The distal transsylvian approach is a validated approach in the treatment of basal ganglia hemorrhage. However, this approach is difficult and prone to complications. The present study was performed to investigate the surgical techniques and prevention of complications of basal ganglia hemorrhage through the distal transsylvian approach. PATIENTS AND METHODS: From January 2015 to January 2018, the authors treated 40 cases of basal ganglia hemorrhage using the distal transsylvian approach. The surgical video recordings and the patients' clinical data were retrospectively analyzed. The authors discussed the surgical techniques and prevention of complications through the distal transsylvian approach. RESULTS: Thirty-eight cases of basal ganglia hemorrhage were successfully treated through the distal transsylvian approach. The other 2 cases were converted to the transcortical transtemporal approach. In the early cases, complications occurred in 3 stages: sylvian fissure dissection, insula lobectomy, and hematoma removal. In the subsequent cases, the authors implemented appropriate surgical techniques to prevent complications. CONCLUSION: Basal ganglia hemorrhage can be treated through the distal transsylvian approach, but not in all patients. The distal transsylvian approach is highly technical and more problematic than the transcortical transtemporal approach. Mastering certain operative skills can reduce the surgical complications.


Assuntos
Hemorragia dos Gânglios da Base/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Feminino , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Estudos Retrospectivos
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(3): 442-449, 2020 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-32597086

RESUMO

This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured in vitro, and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.


Assuntos
Carcinoma Hepatocelular , Meios de Cultivo Condicionados , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Humanos , Neoplasias Hepáticas/patologia
16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(1): 105-111, 2020 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-32096383

RESUMO

The article aims to explore the optimal concentration of arsenic trioxide (As 2O 3) on HepG2 of liver cancer cells, and the effect of As 2O 3 on the migration, invasion and apoptosis of HepG2 cells. In this study, the activity of HepG2 cells treated with 0, 1, 2, 4, 8, 16, 32 µmol/L As 2O 3 was tested by CCK-8 method, the semi-inhibitory concentration (IC50) was calculated, and the morphological changes of HepG2 cells were observed after the action of As 2O 3 at IC50 concentration for 12, 24, 48 h. The effect of As 2O 3 on cell migration and invasion ability was verified by wound healing experiment and Transwell invasion experiment. Western blot and qRT-PCR were used to detect the effects of As 2O 3 on the gene and protein expression levels related to cell migration, invasion and apoptosis. The results showed that, compared with the control group, the activity of HepG2 cells decreased with the increase of the concentration of As 2O 3 treatment, showing a dose-dependent effect, and its IC50 was 7.3 µmol/L. After 24 hours' treatment with 8 µmol/L As 2O 3, HepG2 cells underwent significant apoptosis, and its migration and invasion abilities were significantly reduced. In addition, the protein expression levels of RhoA, Cdc42, Rac1 and matrix metalloproteinase-9 (MMP-9) were down-regulated, the protein and mRNA expression levels of anti-apoptotic gene Bcl-2 were significantly down-regulated, and the protein and mRNA expression levels of pro-apoptotic genes Bax and Caspase-3 were significantly up-regulated. The above results indicate that certain concentration of As 2O 3 can inhibit the migration and invasion of hepatocellular carcinoma cells and promote the apoptosis of hepatocellular carcinoma cells.


Assuntos
Apoptose/efeitos dos fármacos , Trióxido de Arsênio/farmacologia , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Proliferação de Células , Células Hep G2 , Humanos , Invasividade Neoplásica
17.
Chemphyschem ; 20(10): 1376-1381, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30701657

RESUMO

Thermodynamic properties of alkali and alkaline earth metal amides are critical for their performance in hydrogen storage as well as catalytic ammonia synthesis. In this work, the ammonia equilibrium concentrations of LiNH2 , KNH2 and Ba(NH2 )2 at ca.10 bar of hydrogen pressure and different temperatures were measured by using a high-pressure gas-solid reaction system equipped with a conductivity meter. Hydrogenation of KNH2 gives the highest ammonia equilibrium concentration, followed by Ba(NH2 )2 and LiNH2 . Based on these data, the entropy and enthalpy changes of the reaction of ANH2 +H2 →AH+NH3 (A=Li, K, and Ba) were obtained from the van't Hoff equation. These thermodynamic parameters provide important information on the understanding of metal amides in catalytic ammonia synthesis reaction.

18.
J Phys Chem A ; 123(29): 6370-6377, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31310124

RESUMO

Molecular dynamics (MD) simulation and experimental methods are used to explore the interaction between the propargyl-terminated polybutadiene (PTPB) binder and plasticizers bis(2,2-dinitropropyl) formal/acetal (BDNPF/A) and dioctyl sebacate (DOS). Flory-Huggins parameters, radial distribution functions, and binding energies between PTPB and plasticizers are calculated using MD simulations. The solubility parameters of PTPB and the plasticizers are calculated by both MD and group contribution method. The mesoscopic dynamics (MesoDyn) is used to simulate the meso-morphology of PTPB and plasticizer blends by converting the results of MD simulation into MesoDyn simulation parameters. The results of simulations and calculations show that PTPB has better compatibility with DOS than with BDNPF/A, and DOS is more suitable as a plasticizer for PTPB. The results of dynamic rheological experiments show that BDNPF/A has little effect on the dynamic viscosity of PTPB, and DOS can significantly reduce the dynamic viscosity of PTPB and has better plasticizing effect on PTPB. Differential scanning calorimetry and dynamic mechanical analysis tests indicate that the DOS and PTPB blend has only one glass transition temperature, while the PTPB and BDNPF/A blend has two glass transition temperatures. Both simulations and experimental results show that the PTPB binder have better compatibility with DOS than with BDNPF/A, and DOS has better plasticization effects on the PTPB binder.

19.
J Am Chem Soc ; 140(44): 14799-14806, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30351925

RESUMO

Early 3d transition metals are not focal catalytic candidates for many chemical processes because they have strong affinities to O, N, C, or H, etc., which would hinder the conversion of those species to products. Metallic Mn, as a representative, undergoes nitridation under ammonia synthesis conditions forming bulk phase nitride and unfortunately exhibits negligible catalytic activity. Here we show that alkali or alkaline earth metal hydrides (i.e., LiH, NaH, KH, CaH2 and BaH2, AHs for short) promotes the catalytic activity of Mn nitride by orders of magnitude. The sequence of promotion is BaH2 > LiH > KH > CaH2 > NaH, which is different from the order observed in conventional oxide or hydroxide promoters. AHs, featured by bearing negatively charged hydrogen atoms, have chemical potentials in removing N from Mn nitride and thus lead to significant enhancement of N2 activation and subsequent conversion to NH3. Detailed investigations on Mn-LiH catalytic system disclosed that the active phase and kinetic behavior depend strongly on reaction conditions. Based on the understanding of the synergy between AHs and Mn nitride, a strategy in the design and development of early transition metals as effective catalysts for ammonia synthesis and other chemical processes is proposed.

20.
Biochem Biophys Res Commun ; 500(2): 462-469, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29660339

RESUMO

Fructose is now such an important component of human diets, and several studies have found that some cancer cells could utilize fructose to overcome low glucose micro-environment, but the study on the role of fructose in glioma is rare. To explore the role of fructose in glioma, we detected the proliferation and colony formation ability of glioma cells in fructose medium, and found that the abilities of proliferation and colony formation of glioma cells in fructose medium were similar with abilities in glucose medium, however, fructose just partly restored proliferation ability of normal glial cells. To explore the mechanism, we compared the expression level of GLUT5 (Glucose transporter type 5) in these cell lines, and the results showed that glioma cell lines had higher GLUT5 expression than normal glial cell lines. And knockdown of GLUT5 could significantly inhabit cell proliferation of glioma cells in fructose medium. Furthermore, we found that GLUT5 was also higher expressed in glioma tissues, and GLUT5 expression correlated significantly with glioma malignancy and poor survival of glioma patients (p < 0.01). In addition, we also demonstrated that knockdown of GLUT5 could significantly inhabit tumor proliferation in vivo, and intake fructose could increase tumor volume prominently. Taken together, our data show that fructose can be used by glioma cells, and restrict the fructose intake or targeting GLUT5 could be efficacious strategies in glioma.


Assuntos
Progressão da Doença , Frutose/metabolismo , Glioma/patologia , Transportador de Glucose Tipo 5/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Glioma/genética , Glucose/deficiência , Transportador de Glucose Tipo 5/genética , Humanos , Masculino , Camundongos Nus , Microglia/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida
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