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1.
Phys Chem Chem Phys ; 26(8): 7072-7082, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345652

RESUMO

The promotion of lithium-ion batteries and sodium-ion batteries is limited by the deficiency of suitable anode materials with desired electrochemical properties. In this work, the models of 2D single-layer SiP are constructed to explore its potential as an anode material for LIBs and SIBs using density functional theory (DFT). The diffusion of Li in bulk SiP is anisotropic. There is a low diffusion energy barrier of 0.28 eV along the X-axis. The low surface exfoliation energy suggests that there is a high probability of preparing 2D single-layer SiP experimentally. Its structure stability is verified by ab initio molecular dynamics (AIMD) simulations at 300 K and 400 K. The intercalation and diffusion behaviors of Li/Na on 2D single-layer SiP indicate that Li/Na tends to diffuse along the X-axis direction of 2D single-layer SiP. The diffusion energy barrier of Li/Na on 2D single-layer SiP is lower compared to that of bulk SiP. The conductivity of 2D single-layer SiP is improved after lithiation due to the upshift of Fermi levels. 2D single-layer SiP has a lower average open circuit voltage (1.50 V for LIBs and 1.08 V for SIBs) and a high theoretical capacity (520 mA h g-1). Hence, 2D single-layer SiP can be an ideal anode material for LIBs and SIBs.

2.
FASEB J ; 38(1): e23388, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38145323

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells that differentiate from myeloid cells, proliferate in cancer and inflammatory reactions, and mainly exert immunosuppressive functions. Nonetheless, the precise mechanisms that dictate both the accumulation and function of MDSCs remain only partially elucidated. In the course of our investigation, we observed a positive correlation between the content of MDSCs especially G-MDSCs and miR-9 level in the tumor tissues derived from miR-9 knockout MMTV-PyMT mice and 4T1 tumor-bearing mice with miR-9 overexpression. Combined with RNA-seq analysis, we identified SOCS2 and SOCS3 as direct targets of miR-9. Additionally, our research unveiled the pivotal role of the CCL5/CCR5 axis in orchestrating the chemotactic recruitment of G-MDSCs within the tumor microenvironment, a process that is enhanced by miR-9. These findings provide fresh insights into the molecular mechanisms governing the accumulation of MDSCs within the framework of breast cancer development.


Assuntos
MicroRNAs , Células Supressoras Mieloides , Neoplasias , Proteína 3 Supressora da Sinalização de Citocinas , Animais , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Células Supressoras Mieloides/patologia , Neoplasias/patologia , Microambiente Tumoral , Proteína 3 Supressora da Sinalização de Citocinas/genética
3.
Mol Cancer ; 22(1): 205, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093288

RESUMO

BACKGROUND: Targeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets. METHODS: Western blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model. RESULTS: We demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape. CONCLUSION: Our results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/genética , Evasão Tumoral/genética , Fosforilação , Antígeno B7-H1/genética , Hibridização in Situ Fluorescente , MicroRNAs/genética , RNA Interferente Pequeno , Proliferação de Células , Linhagem Celular Tumoral , Microambiente Tumoral , Proteína Quinase Ativada por DNA
4.
Cell Rep ; 42(11): 113377, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37922310

RESUMO

ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.


Assuntos
Proteínas de Ligação a RNA , RNA , Camundongos , Animais , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Necroptose , Morte Celular/fisiologia
5.
Front Plant Sci ; 14: 1240196, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711292

RESUMO

The effects of different irrigation and fertilization on potato yield, soil fertility and soil enzyme activity of different varieties under drip irrigation fertilization mode were studied, which could provide support for selecting the best varieties in Northwest China. Three factors and three levels orthogonal experimental design method, a total of nine treatments. The three irrigation levels were W1 (100% crop evapotranspiration (ETC)), W2 (80% ETC) and W3 (60% ETC). The three fertilization levels were F1 (N-P2O5-K2O, 240-120-300 kg ha-1), F2 (180-90-225 kg ha-1) and F3 (120-60-150 kg ha-1). The three varieties were V1 (Feiuritar), V2 (Longshu7) and V3 (Qingshu 9). The results showed that different irrigation and fertilization had significant effects on potato yield, soil fertility and soil enzyme activity in root zone. The highest yield of T5 (80%ETC, 180-90-225 kg ha-1, Qingshu 9) was 49,222.3 kg ha-1. With the increase of fertilizer application rate, potato yield and soil enzyme activity in root zone increased first and then decreased, but soil electrical conductivity (SEC), soil nitrate-N content (SNNC), soil alkali-hydrolyzable nitrogen content (SAHC), soil available potassium (AK), soil available phosphorus (AP), soil ammonium-N content (SANC) and soil organic matter (SOM) in root zone increased continuously. The yield, soil catalase activity, soil urease activity and soil sucrase activity at W2 were 2.81% and 22.2%, 1.84% and 7.04%, 8.26% and 9.62%, 5.34% and 13.36% higher than those at W1 and W3, respectively. The overall trend of soil water content, soil nutrient content and enzyme activity in root zone was 0-20 cm >20-40 cm >40-60 cm soil layer. There were many soil factors affecting tuber yield, among which soil enzyme activity, pH value and root zone conductivity were the key factors. The results showed that T5 (80%ETC, 180-90-225 kg ha-1, Qingshu 9) was the best treatment to improve soil enzyme activity and yield.

6.
PLoS Pathog ; 19(5): e1010979, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37253071

RESUMO

In its simplest form, bacterial flagellar filaments are composed of flagellin proteins with just two helical inner domains, which together comprise the filament core. Although this minimal filament is sufficient to provide motility in many flagellated bacteria, most bacteria produce flagella composed of flagellin proteins with one or more outer domains arranged in a variety of supramolecular architectures radiating from the inner core. Flagellin outer domains are known to be involved in adhesion, proteolysis and immune evasion but have not been thought to be required for motility. Here we show that in the Pseudomonas aeruginosa PAO1 strain, a bacterium that forms a ridged filament with a dimerization of its flagellin outer domains, motility is categorically dependent on these flagellin outer domains. Moreover, a comprehensive network of intermolecular interactions connecting the inner domains to the outer domains, the outer domains to one another, and the outer domains back to the inner domain filament core, is required for motility. This inter-domain connectivity confers PAO1 flagella with increased stability, essential for its motility in viscous environments. Additionally, we find that such ridged flagellar filaments are not unique to Pseudomonas but are, instead, present throughout diverse bacterial phyla.


Assuntos
Bactérias , Flagelina , Flagelina/metabolismo , Bactérias/metabolismo , Flagelos/metabolismo , Pseudomonas/metabolismo , Pseudomonas aeruginosa/metabolismo
7.
Molecules ; 29(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38202588

RESUMO

The demand for the ubiquitous detection of gases in complex environments is driving the design of highly specific gas sensors for the development of the Internet of Things, such as indoor air quality testing, human exhaled disease detection, monitoring gas emissions, etc. The interaction between analytes and bioreceptors can described as a "lock-and-key", in which the specific catalysis between enzymes and gas molecules provides a new paradigm for the construction of high-sensitivity and -specificity gas sensors. The electrochemical method has been widely used in gas detection and in the design and construction of enzyme-based electrochemical gas sensors, in which the specificity of an enzyme to a substrate is determined by a specific functional domain or recognition interface, which is the active site of the enzyme that can specifically catalyze the gas reaction, and the electrode-solution interface, where the chemical reaction occurs, respectively. As a result, the engineering design of the enzyme electrode interface is crucial in the process of designing and constructing enzyme-based electrochemical gas sensors. In this review, we summarize the design of enzyme-based electrochemical gas sensors. We particularly focus on the main concepts of enzyme electrodes and the selection and design of materials, as well as the immobilization of enzymes and construction methods. Furthermore, we discuss the fundamental factors that affect electron transfer at the enzyme electrode interface for electrochemical gas sensors and the challenges and opportunities related to the design and construction of these sensors.


Assuntos
Técnicas Eletroquímicas , Gases , Humanos , Catálise , Eletrodos , Transporte de Elétrons
8.
Artigo em Inglês | MEDLINE | ID: mdl-35954988

RESUMO

The safety situation of hazardous materials (hazmat) accidents during road transportation in China is severe and very serious accidents occurred frequently. Such accidents not only have a huge impact on the environment but also have serious consequences for people and the economy, such as fires and explosions. Therefore, it is necessary to understand the characteristics and laws of road transport accidents of hazmat systematically. This paper investigated 2777 hazmat transportation accidents in China from 2013 to 2019 to identify the characteristics, consequences, and causes of the accident. The results show that August (10.05%) and December (9.76%) are the peak periods of hazmat transportation accidents, while most hazmat transportation accidents occurred in the early morning (6:00-9:00 a.m.) and at noon (9:00 a.m.-12:00 p.m.) hours. For the geographical location, the accidents mainly occurred in the east China (34.35%) and the northwest China areas (14.87%). The main types of hazmat transportation accidents were rollover (35.36%), rear-end (22.58%), and collision (14.87%), where the probability of a major leak was high. The most common hazmat transportation accidents involve gas (17.79%), flammable liquid (56.07%), and corrosive substance (12.28%). The most common consequences of the hazmat transportation accidents were leakage (80.34%), followed by fire release (8.32%) and explosion release (2.34%). Human factor (26.74%) is the main cause of hazmat transportation accidents. These findings could help hazmat transportation managers and planners develop appropriate measures for improving hazmat transportation safety.


Assuntos
Substâncias Perigosas , Meios de Transporte , Acidentes , China/epidemiologia , Humanos , Probabilidade
9.
Nutr Cancer ; 74(9): 3051-3057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35441576

RESUMO

Common gastric diseases include chronic gastritis, gastric ulcers and gastric cancer. The etiology of gastric diseases is complicated, including genetics, diet, excessive smoking and drinking, environmental factors, and bacterial infections. As live microorganisms, probiotics can confer health benefits to the host. At present, probiotics have been widely used in the preparation of foods, health products, and medicines. Due to their positive effects in improving diarrhea, constipation, alleviating allergies, enhancing immunity, and maintaining intestinal homeostasis, studies worldwide have focused on whether probiotics also provide therapeutic effects on gastric diseases. Thus, this review summarizes the possible mechanism of probiotics in the treatment of gastric diseases and provides a reference for expanding not only their application but also that of other microecological agents.


Assuntos
Probióticos , Neoplasias Gástricas , Constipação Intestinal , Diarreia , Humanos , Intestinos , Probióticos/uso terapêutico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/terapia
10.
Small ; 18(18): e2200524, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35362260

RESUMO

High-entropy oxides (HEOs) are gradually becoming a new focus for lithium-ion battery (LIB) anodes due to their vast element space/adjustable electrochemical properties and unique single-phase retention ability. However, the sluggish kinetics upon long cycling limits their further generalization. Here, oxygen vacancies with targeted functionality are introduced into rock salt-type (MgCoNiCuZn)O through a wet-chemical molten salt strategy to accelerate the ion/electron transmission. Both experimental results and theoretical calculations reveal the potential improvement of lithium storage, charge transfer, and diffusion kinetics from HEO surface defects, which ultimately leads to enhanced electrochemical properties. The currently raised strategy offers a modular approach and enlightening insights for defect-induced HEO-based anodes.

11.
Environ Toxicol ; 37(2): 192-200, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34661962

RESUMO

Tanshinone IIA is the active constituent extracted from Salvia Miltiorrhza. Numerous studies have shown that Tanshinone IIA could inhibit tumor proliferation and metastasis, including gastric cancer. However, the effect of Tanshinone IIA on gastric cancer cell stemness stays unclear. Here, we found that Tanshinone IIA could reduce gastric cancer cell stemness through detecting spheroid-forming, flow cytometry analysis, and the expression of stemness markers (OCT3/4, ALDH1A1, and CD44). Mechanistically, Tanshinone IIA increased the level of lipid peroxides and decreased glutathione level in gastric cancer cells, both of which are the markers of ferroptosis. Similarly, ferroptosis inducers (erastin, sulfasalazine, and sorafenib) reduced gastric cancer cell stemness. Additionally, the inhibitory effects of Tanshinone IIA on GC cell stemness were reversed by ferroptosis inhibitor (Fer-1) or overexpression of SLC7A11, which is a critical ferroptosis inhibitor. Therefore, we revealed that Tanshinone IIA inhibited the stemness of gastric cancer cells partly through inducing ferroptosis.


Assuntos
Antineoplásicos Fitogênicos , Ferroptose , Neoplasias Gástricas , Abietanos , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Gástricas/tratamento farmacológico
12.
Artigo em Inglês | MEDLINE | ID: mdl-34886099

RESUMO

This paper proposes a measurement of risk (MOR) method to recognize risky driving behavior based on the trajectory data extracted from surveillance videos. Three types of risky driving behavior are studied in this paper, i.e., speed-unstable driving, serpentine driving, and risky car-following driving. The risky driving behavior recognition model contains an MOR-based risk evaluation model and an MOR threshold selection method. An MOR-based risk evaluation model is established for three types of risky driving behavior based on driving features to quantify collision risk. Then, we propose two methods, i.e., the distribution-based method and the boxplot-based method, to determine the threshold value of the MOR to recognize risky driving behavior. Finally, the trajectory data extracted from UAV videos are used to validate the proposed model. The impact of vehicle types is also taken into consideration in the model. The results show that there are significant differences between threshold values for cars and heavy trucks when performing speed-unstable driving and risky car-following driving. In addition, the difference between the proportion of recognized risky driving behavior in the testing dataset compared with that in the training dataset is limited to less than 3.5%. The recognition accuracy of risky driving behavior with the boxplot- and distribution-based methods are, respectively, 91% and 86%, indicating the validation of the proposed model. The proposed model can be widely applied to risky driving behavior recognition in video-based surveillance systems.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Automóveis , Veículos Automotores , Assunção de Riscos
13.
Microb Pathog ; 159: 105151, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34450200

RESUMO

CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cells, are reported to contribute to local immunosuppression. However, the presence of DP T cells in Helicobacter. pylori -induced gastritis and their relationship with disease prognosis has yet to be elucidated. In this study, a chronic gastritis model was established by infecting mice with Helicobacter felis. Gastric-infiltrating lymphocytes were isolated from these mice and analyzed by flow cytometry. The frequency of DP T cells in H. felis-induced gastritis mice was higher than that in uninfected mice. The gastric DP T cells were derived from lamina propria cells but were predominantly distributed in the gastric epithelial layer. These gastric DP T cells also exhibited anti-inflammatory functions, and they inhibited the maturation of dendritic cells and proliferation of CD4+ T lymphocytes in vitro. Elimination of DP T cells simultaneously resulted in severe gastritis and a reduction of H. felis load in vivo. Finally, vaccine mixed with different adjuvants was used to explore the relationship between vaccine efficacy and DP cells. Silk fibroin as the vaccine delivery system enhanced vaccine efficacy by reducing the number of DP T cells. This study demonstrated that DP T cells perform an immunosuppressive role in Helicobacter felis-induced gastritis, and consequently, DP T cells may affect disease prognosis and vaccine efficacy.


Assuntos
Helicobacter felis , Linfócitos T , Animais , Linfócitos T CD4-Positivos , Epitélio , Mucosa Gástrica , Inflamação , Camundongos
14.
Chem Commun (Camb) ; 57(66): 8158-8161, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34318798

RESUMO

An oxygen-doped, hollow, porous NiCoP nanocage (O-NiCoP Cages) electrocatalyst was synthesized derived from Ni-Co Prussian blue analogs. O-NiCoP Cages exhibited an overpotential of 310 mV at 10 mA cm-2 and a Tafel slope of 84 mV dec-1, significantly higher than that of undoped NiCoP nanocages, and also better than that of RuO2 and several reported phosphide electrocatalysts. This work provides a new strategy for the design of highly efficient oxygen evolution reaction (OER) electrocatalysts based on hollow, nanostructured and heteroatom-doped metal phosphides.

15.
J Colloid Interface Sci ; 604: 680-690, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34280766

RESUMO

Efficient, low-cost, and robust electrocatalysts development for overall water splitting is highly desirable for renewable energy production yet still remains challenging. In this work, Co9S8 nanoneedles arrays are synergistically integrated with NiFe-layered double hydroxide (NiFe-LDH) nanosheets to form Co9S8@NiFe-LDH core-branch hierarchical architectures supported on nickel foam (Co9S8@NiFe-LDH HAs/NF). The Co9S8@NiFe-LDH HAs/NF exhibits high catalytic performances for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with overpotential of 190 and 145 mV at 10 mA cm-2, respectively. The density functional theory calculations predict that the synergy between Co9S8 and NiFe-LDH contributes to the high catalytic performance by lowering the energy barrier of HER. When used as both anode and cathode electrocatalyst, it can deliver 10 mA cm-2 at a low cell voltage of 1.585 V with excellent long-term durability. This work opens a new avenue toward the exploration of highly efficient and stable electrocatalyst for overall water splitting.

16.
Front Immunol ; 12: 624725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084160

RESUMO

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.


Assuntos
MicroRNAs/imunologia , Neoplasias/imunologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Animais , Antineoplásicos/uso terapêutico , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Progressão da Doença , Humanos , Imunoterapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/uso terapêutico , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Fenótipo , Evasão Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
17.
Stem Cell Res Ther ; 12(1): 325, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090492

RESUMO

BACKGROUND: Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness. METHODS: Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. RESULTS: MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. CONCLUSION: MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.


Assuntos
Ferroptose , MicroRNAs , Neoplasias Gástricas , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Células-Tronco Neoplásicas , Neoplasias Gástricas/genética
18.
Helicobacter ; 26(4): e12813, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33938607

RESUMO

BACKGROUND: Recent studies and clinical samples have demonstrated that Helicobacter pylori could induce the downregulation of miR-375 in the stomach and promote gastric carcinogenesis. However, whether the immune cells are affected by Helicobacter pylori due to the downregulation of miR-375 is unclear. MATERIALS AND METHODS: In this study, we constructed an overexpression and knockdown of miR-375 and Helicobacter pylori infection cell models in vitro. In addition, the maturity of dendritic cells (DCs) and the expression of IL-6, IL-10, and VEGF at the transcriptional and translational levels were analyzed. Changes in the JAK2-STAT3 signaling pathway were detected. In vivo, the number changes in CD4+ T and CD8+ T cells and the size changes of tumors via models of transplantable subcutaneous tumors were also analyzed. RESULTS: A cell model of Helicobacter pylori and gastric cancer was used to identify the expression of miR-375 and the maturity of dendritic cells. This study found that Helicobacter pylori could downregulate miR-375, which regulates the expression of cytokines IL-6, IL-10, and VEGF in the stomach. MiR-375 regulated the expression of cytokines IL-6, IL-10, and VEGF through the JAK2-STAT3 signaling pathway in vitro. In addition, we found that Helicobacter pylori regulates the maturation of dendritic cells through miR-375. These results were further verified in vivo, and miR-375 diminishes tumor size was also demonstrated. This study showed that immature DCs caused a decrease in the number of CD4+ and CD8+ T cells. CONCLUSIONS: This study demonstrated that Helicobacter pylori can inhibit miRNA-375 expression in the stomach. Downregulated miR-375 activates the JAK2-STAT3 pathway. Activating the JAK2-STAT3 signaling pathway promotes the secretion of IL-6, IL-10, and VEGF, leading to immature differentiation of DCs and induction of gastric cancer.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , MicroRNAs/genética , Neoplasias Gástricas , Diferenciação Celular , Células Dendríticas , Regulação para Baixo , Mucosa Gástrica , Infecções por Helicobacter/complicações , Humanos , Neoplasias Gástricas/etiologia
19.
Plant Cell ; 33(6): 2015-2031, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-33751120

RESUMO

Acquisition of nutrients from different species is necessary for pathogen colonization. Iron is an essential mineral nutrient for nearly all organisms, but little is known about how pathogens manipulate plant hosts to acquire iron. Here, we report that AvrRps4, an effector protein delivered by Pseudomonas syringae bacteria to plants, interacts with and targets the plant iron sensor protein BRUTUS (BTS) to facilitate iron uptake and pathogen proliferation in Arabidopsis thaliana. Infection of rps4 and eds1 by P. syringae pv. tomato (Pst) DC3000 expressing AvrRps4 resulted in iron accumulation, especially in the plant apoplast. AvrRps4 alleviates BTS-mediated degradation of bHLH115 and ILR3(IAA-Leucine resistant 3), two iron regulatory proteins. In addition, BTS is important for accumulating immune proteins Enhanced Disease Susceptibility1 (EDS1) at both the transcriptional and protein levels upon Pst (avrRps4) infections. Our findings suggest that AvrRps4 targets BTS to facilitate iron accumulation and BTS contributes to RPS4/EDS1-mediated immune responses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Ferro/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/imunologia , Proteínas de Bactérias/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação , Imunidade Vegetal/genética , Plantas Geneticamente Modificadas , Pseudomonas syringae/metabolismo , Pseudomonas syringae/patogenicidade , Ubiquitina-Proteína Ligases/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-33466625

RESUMO

Urban rail transit has become one of the indispensable modes of public transportation in large cities. Escalators are ubiquitous in metro stations, as passengers typically use escalators when entering or leaving a metro station. Thus, escalators have become an accident-prone location. To develop suitable prevention strategies, it is necessary to understand the risk factors that affect the severity of escalator accidents. This study analyzed 967 escalator passenger accidents that occurred in the Guangzhou Metro from 2013 to 2015. The Haddon matrix was used to evaluate the interaction of humans, escalators, and environmental factors before, during, and after accidents. Then, the contributing factors associated with the severity levels were determined based on chi-square tests. Passengers aged 66 years and older are more vulnerable to serious injuries (p < 0.001), and previous health conditions are significantly related to the severity of the passenger's injuries (p = 0.002). The weather conditions (rainy days) are also significantly related to the severity of escalator accident injuries (p = 0.039), and injured people with head injuries are at greater risk of being severely injured (p < 0.001). The analysis results of these risk factors can provide theoretical support for the metro operators to develop reasonable and effective preventive measures to reduce the escalator risk.


Assuntos
Traumatismos Craniocerebrais , Ferimentos e Lesões , Acidentes , Idoso , China/epidemiologia , Cidades/epidemiologia , Elevadores e Escadas Rolantes , Humanos , Ferimentos e Lesões/epidemiologia
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