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In the global wave of digitization, digital economic agglomeration, as an emerging model, profoundly impacts the economy, environment, and society. Countries worldwide are formulating strategies and policies to promote the development of digital economic agglomeration, yet they also face challenges of widening digital divide and environmental sustainability. Existing research primarily focuses on the positive effects of the digital economy, with limited assessment of the dual effects of digital economic agglomeration on sustainable development. This study utilizes panel data from 282 Chinese cities between 2011 and 2021, employing a two-tier stochastic frontier model. It reexamines the dual impacts and intrinsic mechanisms of digital economic agglomeration, attempting to capture regional and temporal variations in the dual effects to address this research gap. The study shows that: (1) The positive effect of digital economy agglomeration is much more than the negative effect, resulting in a positive net effect that shows an overall increasing trend with significant regional disparities. (2) Digital economic agglomeration has a significant negative spatial spillover effect, promoting local inclusive green growth while inhibiting inclusive green growth in neighboring cities. (3) Regarding the mediating mechanisms, industrial structure, technological innovation and resource allocation efficiency have positive indirect effects on inclusive green growth, while environmental regulation intensity has a negative indirect effect, and it has a nonlinear effect under the threshold constraint of the mediating mechanisms. This study provides policy insights for promoting inclusive green growth, emphasizing the need to consider regional differences in resource distribution, ecological environment, and social demands. It advocates for the organic integration of the digital economy across different regions, reducing polarization effects, and enhancing diffusion effects.
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Meio Ambiente , Indústrias , Cidades , Difusão , Políticas , China , Desenvolvimento EconômicoRESUMO
An efficient phase stabilization method is required in quantum key distribution (QKD) systems for stability in practical applications. The existing active phase compensation method has limitations in multi-node network applications, especially in network-scale applications based on measurement-device-independent QKD systems. In this study, we propose a local active phase compensation scheme that can realize phase compensation independently for each interferometer node. We performed experimental demonstrations in the BB84 phase encoding system based on a Faraday-Michelson interferometer. The average QBER rates of the system under two different forms of the reference light were found to be 1.9% and 1.6%. This scheme can also be applied to other QKD systems and has potential for application in future quantum communication networks.
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The epithelial-mesenchymal transition (EMT) is crucial for cancer progression. Evidence has shown that miR-22 and miR-214 play a key role in colon cancer progression; however, the underlying mechanism remains to be known. The effects of miR-22 and miR-214 on EMT are contradictory in different cancers, and whether miR-22 and miR-214 are involved in the colon cancer EMT process needs to be elucidated. In this study, we evaluated the exact role and the regulation mechanism of miR-22 and miR-214 in colon cancer. After transfection with miR-22 expression vector, the cell proliferation and migration capacity of HCT116 and RKO cells were significantly suppressed. Also, E-cadherin was increased and vimentin was decreased by miR-22 overexpression. Similar effects were also observed after miR-214 expression vector transfection. Dual-luciferase reporter confirmed that BCL9L is the target gene of both miR-22 and miR-214. Silencing of BCL9L inhibits cell proliferation and migration, and the expression of E-cadherin and vimentin was also altered by BCL9L knockdown, which was consistent with miR-22 or miR-214 transfection. Furthermore, miR-22 and miR-214 inhibited tumor growth in nude mice. Moreover, although the association between BCL9L's lower expression and longer survival time was statistically nonsignificant, a trend existed; further studies in a larger cohort are needed. Collectively, these data suggest that miR-22 and miR-214 inhibit cell proliferation, migration, and EMT of colon cancer, most likely by targeting BCL9L.-Sun, R., Liu, Z., Han, L., Yang, Y., Wu, F., Jiang, Q., Zhang, H., Ma, R., Miao, J., He, K., Wang, X., Zhou, D., Huang, C. miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signliang in colon cancer.
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Proliferação de Células/genética , Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Fatores de Transcrição/genética , Via de Sinalização Wnt/genética , Animais , Apoptose/genética , Caderinas/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias do Colo/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HEK293 , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Vimentina/genéticaRESUMO
Amphiphilic biomembrane structures determine significant biological functions and are extensively used as structure models to learn from and study nature. Many biomimetic amphiphilic membranes have been established to connect natural and artificial substances. In this paper, taking advantage of the intercalation and assembly properties of the layered double hydroxides (LDHs), the amphiphilic LDHs/arachidic acid (AA) nanocomposite Langmuir-Blodgett (LB) ultrathin films (UTFs) were fabricated by the LB technology. The CdTe quantum dots (QDs) were incorporated into the LB monolayers via a layer-by-layer (LbL) method based on the electrostatic interaction between LDHs and CdTe QDs. The amphiphilic (CdTe QDs@LDHs/AA) n nanocomposite LB UTFs were composed of CdTe QDs@LDHs hydrophilic segments and hydrophobic layers formed by the long alkyl chain of AA. Because of the spacing effect of amphiphilic AA, the fluorescence intensity of CdTe QDs was enhanced about 10-fold, and the fluorescence lifetimes (38.96 ns vs 17.63 ns) and quantum yield (QY %) (17.56 vs 5.96) have been improved compared to that of the counterpart by the LbL method. The fluorescence intensity of CdTe QDs increased by about fivefolds in the presence of LDHs compared with the counterpart without LDHs, which can be attributed to the two-dimensional confinement effect of LDHs. The amphiphilic nanocomposite LB UTFs were used to detect volatile organic compounds (VOCs) with various polarities. The amphiphilic nanocomposite LB UTFs exhibited two kinds of fluorescence response to VOCs: irreversible fluorescence quenching for amine VOCs with strong polarity and reversible fluorescence enhancement for non-amine VOCs. The fluorescence response mechanism was investigated and can be attributed to the amphiphilic structure of the LB UTFs and the selective adsorption of different VOC molecules. Therefore, this fluorescence quenching/enhancement dual-model response of amphiphilic nanocomposite LB UTFs can be applied into the selective detection of VOCs.
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Sargentodoxa cuneata decoction has been used to treat arthritis in China for hundreds of years. Herein, the polysaccharide fraction (PSC) purified from S. cuneata was evaluated for its inâ vitro and inâ vivo anti-inflammatory effects. PSC and its sub-fractions PSCA-1 and PSCB-1 significantly suppressed nitric oxide (NO) release in LPS-induced RAW264.7 cells by down regulating the inducible nitric oxide synthase (iNOS) level. Furthermore, PSC markedly inhibited carrageenan induced rat hind paw edema, decreased in hind paw, serum and liver malondialdehyde (MDA) levels and prostaglandin E2 (PGE2 ) levels. In addition, PSC increased superoxide dismutase (SOD) activity in serum and liver of the rats. These results revealed that the polysaccharide obtained from S. cuneata (PSC) possessed potent anti-inflammatory activity and may be one of the important bioactive constituents from the plant responsible for the anti-arthritis effect.
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Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Magnoliopsida/química , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
Promoting non-trembling thermogenesis of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) helps prevent obesity. MiR-23b is highly expressed in adipose tissue-derived exosomes obtained from obese people, but the role of exosomal miR-23b in regulating thermogenesis and obesity progression remains to be further explored. Here, a mouse obesity model was established through high-fat diet (HFD), and inguinal WAT (iWAT)-derived exosomes and miR-23b antagomir were administered by intraperitoneal injection. The results showed that WAT-derived exosomal miR-23b upregulated body weight and adipocyte hypertrophy and enhanced insulin resistance. Moreover, exosomal miR-23b restrained mtDNA copy number and the expression of genes related to thermogenesis and mitochondrial biogenesis in BAT, and suppressed the expression of WAT browning-related genes under cold stimulation, indicating that exosomal miR-23b hindered non-trembling thermogenesis of BAT and WAT browning. Mechanism studies found that miR-23b targeted Elf4 to inhibit its expression. And Elf4 bound to the GLP-1R promoter region to promote GLP-1R transcription. In addition, silencing miR-23b effectively abolished the inhibitory effect of WAT-derived exosomes on thermogenic gene expression and mitochondrial respiration in adipocytes isolated from BAT and iWAT, which was reversed by GLP-1R knockdown. In conclusion, WAT-derived exosomal miR-23b suppressed thermogenesis by targeting Elf4 to regulate GLP-1R transcription, which contributed to the progression of obesity.
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Adipócitos Brancos , Exossomos , Camundongos Endogâmicos C57BL , MicroRNAs , Obesidade , Termogênese , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Termogênese/genética , Exossomos/metabolismo , Masculino , Camundongos , Adipócitos Brancos/metabolismo , Obesidade/metabolismo , Obesidade/genética , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Tecido Adiposo Marrom/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.
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Antineoplásicos Fitogênicos , Neoplasias Colorretais , Flavonoides , Glycyrrhiza , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Masculino , Camundongos , Regulação Alostérica/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , Flavonoides/química , Glycyrrhiza/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The outbreak of COVID-19 has brought global poverty to the forefront, and existing research suggests that socially responsible supply chains play an important role in poverty alleviation. However, there is limited research on how to improve the performance of socially responsible supply chains. This study innovatively chooses a dual perspective, i.e., companies and farmers in contract farming, the dominant model of socially responsible supply chains in Chinese agriculture, as the research object. Furthermore, it examines the role of social capital on the performance of socially responsible supply chains, as well as the moderating role of supply chain transparency, in order to find out how to improve the stakeholder performance. The empirical results found that the factors affecting socially responsible supply chain performance differed between the dual perspectives. From the firm's perspective, all three dimensions of social capital (shared values, communication and reciprocity) have a significant positive effect on socially responsible supply chain performance (income increase), while supply chain transparency only positively moderates between communication and income increase. From the farmers' perspective, only reciprocity and shared values had a significant positive effect on income increase; interestingly, supply chain transparency negatively moderated the relationship between reciprocity and income increase. This study expands the role of social capital theory, and the dual perspective examination provides insights for performance improvement of companies and farmers in socially responsible supply chains, as well as guidance for promoting sustainable social development.
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Introduction: In 2020, the outbreak of COVID-19 has forced consumers to shift their consumption patterns online. However, the problem of online fraud in green agricultural products seriously undermines consumer trust and is detrimental to the sustainable consumption of green agricultural products. Therefore, it is particularly important to enhance consumers' trust in online sellers. This study aims to investigate how the product environmental information transparency(soil information transparency and water information transparency) affects online consumers' purchasing behavior of green agricultural products. Methods: This study constructs a theoretical framework of "product environmental information transparency - online consumer trust - online purchase behavior".We conducted an online randomized questionnaire to collect data from a sample of 512 consumers who had experience buying green agricultural products online fitted a structural equation model (SEM). Results: The results show that (1) the two dimensions of product environmental information transparency have different effects on different dimensions of online consumer trust. Among them, soil information transparency has a significant positive effect on competence trust, while it does not have a significant positive effect on benevolence trust. Water information transparency has a significant positive effect on both dimensions of online consumer trust, (2) online consumer trust has a significant positive effect on online consumer purchase behavior, and (3) competence trust has a significant positive effect on benevolence trust. Discussion: Our study shows that consumer trust in merchants is significantly enhanced by increasing the transparency of environmental information about green agricultural products. different dimensions of environmental information transparency have different effects on different dimensions of online consumer trust. Product information transparency is proposed as a tool for producers to use in the online marketing of green agricultural products. Consumers' access to information can be improved through online public disclosure of environmental quality indicators in the production process of green agricultural products, and ultimately enhance online consumption of green agricultural products.
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[This corrects the article DOI: 10.1371/journal.pone.0239427.].
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Plants adapt to high altitudes by adjusting the characteristics of their above and underground organs. Identifying the species-specific plant traits changed in response to altitude is essential for understanding ecophysiological processes at the ecosystem level. Multiple studies analyzed the effects of altitude on above and underground organ traits in different species. Yet, little is known about those responses in the alpine Fritillaria przewalskii Maxim. (Liliaceae). F. przewalskii is a perennial medicinal plant with meager annual growth and vanishing wild populations. We analyzed leaf and bulb functional traits, and their allometric relationships in F. przewalskii plants grown at three altitudes: 3000, 2700, and 2400 m. Leaf thickness, leaf biomass, leaf biomass allocation, and the aboveground:underground ratio increased significantly with increasing altitude. Conversely, bulb allocation decreased at higher altitudes. The altitude influenced the allometric growth trajectories of specific leaf and bulb traits: higher altitudes led to thicker and broader leaves and changed the shape of the bulbs from more circular, which is ideal (at 2700 m), to more elongated (at 3000 m). Those variations had remarkable ecological significance. Hence, bulb biomass is the largest at 2700 m of altitude for which their vertical and longitudinal ratio is unaffected. which is economically favorable. Our findings show that F. przewalskii has a notable potential of growth and morphological plasticity along the altitude gradient and that 2700 m might be ideal for developing its artificial cultivation.
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Altitude , Fritillaria/anatomia & histologia , Fritillaria/crescimento & desenvolvimento , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/anatomia & histologia , Caules de Planta/crescimento & desenvolvimento , BiomassaRESUMO
The adrenergic system contributes to the stress-induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE-induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE-induced phosphorylation of cAMP response element-binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR-373 and transcriptionally activated its expression. miR-373 expression was shown to be necessary for NE-induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR-373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1-miR-373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer.
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Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Neoplasias do Colo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Norepinefrina/farmacologia , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Norepinefrina/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Brassinosteroids (BRs) regulate plant growth and stress responses. BRASSINOSTEROID-INSENSITIVE 1 (BRI1) is a BR receptor that perceives BRs and subsequently activates BR signaling. However, how BR contents and BRI1 expression levels affect the drought resistance of tomato requires further investigation. Here, we exogenously applied 24-epibrassinolide (EBR) and brassinazole (Brz) to tomato plants and generated different transgenic tomato SlBRI1 overexpression lines to study the drought stress response. Our results showed that EBR application 3 days before drought stress increased the contents of BRs and decreased abscisic acid (ABA) and reactive oxygen species (ROS), after which stomatal aperture and drought resistance eventually increased. Brz application reduced the drought resistance. Astonishingly, overexpression of 35S:SlBRI1, which increased BR signaling intensity, led to slightly improved contents of ABA and ROS and ultimately reduced both stomatal aperture and drought resistance. Moreover, plants expressing SlBRI1 driven by a stress-inducible promoter (Atrd29A) also exhibited reduced plant drought resistance. In all cases, enhancing the BR signaling intensity reduced antioxidant enzyme activity and reduced the expression of drought stress-related genes, ultimately compromising the drought resistance. Additionally, SlBRI1 mutants with altered brassinolide sensitivity (abs), which was weak BR signaling, exhibited significantly increased drought resistance. Therefore, our results reveal that BR contents positively regulated tomato drought resistance and that BR signaling intensity via BRI1 was negatively related to the drought resistance. These imply that the increased drought resistance in response to BRs is a newly discovered BR signaling branch that is located downstream of BRs and that differs from that of BRI1.
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Brassinosteroides/metabolismo , Resistência à Doença , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/biossíntese , Proteínas Quinases/biossíntese , Transdução de Sinais , Solanum lycopersicum , Desidratação , Solanum lycopersicum/enzimologia , Solanum lycopersicum/genética , Proteínas de Plantas/genética , Proteínas Quinases/genéticaRESUMO
Protein immobilization is of significant interest for applications in biosensing, drug delivery and bioconversion, and challenges still remain for the in vitro immobilization and application of proteins. Due to it being non-specific to species, easy to express in cells and able to exhibit fluorescence after expression without the need for cofactors or chaperones, green fluorescent protein (GFP), together with its differently colored mutants, has been widely studied and applied. This article reports the fabrication of enhanced green fluorescent protein (EGFP)/layered double hydroxide nanosheet (EGFP/LDH)n ultrathin films (UTFs) via a layer-by-layer assembly technique based on electrostatic and hydrogen-bond interactions, and this realized the immobilization of EGFP. The obtained UTFs show a long-range-ordered periodic layered stacking structure and strong fluorescence originating from EGFP, which also retains its predominant ß-barrel structure well in the LDH laminates. The inorganic LDH laminates play an important role in protecting and improving the structure and properties of the EGFP in the UTFs. Furthermore, the UTFs exhibit a reversible fluorescence response between different pH environments or different wet or dry environments, and also could detect some small biological medicine molecules such as protoporphyrin, and thus they have the potential to be a novel type of biological fluorescence sensor.
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The interactions occurring between a virus and a host cell during a viral infection are complex. The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. A proteomic approach using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography-tandem mass spectrometry identification was conducted on the TGEV-infected ST cells. The results showed that the 4-plex iTRAQ-based quantitative approach identified 4,112 proteins, 146 of which showed significant changes in expression 48 h after infection. At 64 h post infection, 219 of these proteins showed significant change, further indicating that a larger number of proteomic changes appear to occur during the later stages of infection. Gene ontology analysis of the altered proteins showed enrichment in multiple biological processes, including cell adhesion, response to stress, generation of precursor metabolites and energy, cell motility, protein complex assembly, growth, developmental maturation, immune system process, extracellular matrix organization, locomotion, cell-cell signaling, neurological system process, and cell junction organization. Changes in the expression levels of transforming growth factor beta 1 (TGF-ß1), caspase-8, and heat shock protein 90 alpha (HSP90α) were also verified by western blot analysis. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Therefore, this study provides a solid foundation for further investigation, and will likely help us to better understand the mechanisms of TGEV infection and pathogenesis.
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Gastroenterite Suína Transmissível/genética , Proteoma/genética , Testículo/metabolismo , Animais , Linhagem Celular , Cromatografia Líquida , Gastroenterite Suína Transmissível/metabolismo , Gastroenterite Suína Transmissível/patologia , Gastroenterite Suína Transmissível/virologia , Regulação Viral da Expressão Gênica , Masculino , Suínos , Testículo/patologia , Testículo/virologia , Vírus da Gastroenterite Transmissível/genética , Vírus da Gastroenterite Transmissível/patogenicidadeRESUMO
UNLABELLED: Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment. IMPLICATIONS: miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.