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OBJECTIVES: To investigate the potential mechanisms of shikonin in preventing and treating periodontitis using network pharmacology and molecular docking methods. MATERIALS AND METHODS: The targets of shikonin were obtained in TCMSP and SEA databases, and targets of periodontitis were gathered from the OMIM, GeneCards and Drugbank Databases. The intersecting targets were entered into the DAVID database to obtain the relevant biological functions and pathways by GO and KEGG enrichment analysis. The obtained targets were analysed the protein-protein interaction (PPI) in STRING platform. In Cytoscape 3.8.0, the network analysis function with the MCODE plug-in were used to obtain the key targets, of shikonin and periodontitis. Molecular docking and molecular dynamics simulation (MD) were used to assess the affinity between the shikonin and the key targets. RESULTS: Shikonin was screened for 22 targets and periodontitis was screened for 944 targets, the intersecting targets were considered as potential therapeutic targets. The targets played important roles in cellular response to hypoxia, response to xenobiotic stimulus and positive regulates of apoptotic process by GO enrichment analysis. 10 significant pathways were analyzed by KEGG, such as human cytomegalovirus infection and PI3K-Akt signaling pathway, etc. Cytoscape software screened the key genes including AKT1, CCL5, CXCR4, PPARG, PTEN, PTGS2 and TP53. Molecular docking and MD results showed that shikonin could bind stably to the targets. CONCLUSIONS: The present study enriched the molecular mechanisms in periodontitis with shikonin, providing potential therapeutic targets for periodontitis.
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Simulação de Acoplamento Molecular , Naftoquinonas , Farmacologia em Rede , Periodontite , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Periodontite/tratamento farmacológico , Humanos , Mapas de Interação de Proteínas , Simulação de Dinâmica Molecular , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Enterococcus faecium (E. faecium) stands as a prominent pathogen contributing to Gram-positive bacterial infections in individuals who have undergone liver transplantation. CASE PRESENTATION: A 66-year-old male with a three-year history of treated anxiety disorder was admitted to our hospital due to recurrent abdominal distension and oliguria. He was diagnosed with hepatic veno-occlusive disease (HVOD), hepatic failure, pneumonia, renal insufficiency and abdominal ascites. A liver transplantation procedure was performed, but the patient's infection index increased on the first day after surgery. Empirical antibiotic therapy with ceftriaxone and meropenem and preventive antifungal therapy were applied. Sputum culture, blood culture, ascites culture and bronchoalveolar lavage fluid (BALF) next-generation sequencing (NGS), revealed the presence of E. faecium. Given the application of various nephrotoxic immunosuppressive agents after liver transplantation, pre-existing renal insufficiency, severe bone marrow suppression, and a history of anxiety disorder treated with sertraline, contezolid was added for the treatment of the Gram-positive bacterial infection. Sixteen days after surgery, cultures from ascites and sputum yielded negative results for fungi and bacteria. Contezolid was subsequently discontinued without any reported adverse events during follow-up. CONCLUSION: Treatment with contezolid as the first-line therapy for sepsis and pneumonia caused by E. faecium following liver transplantation has shown satisfactory efficacy and safety. Therefore, contezolid may hold great promise for managing this life-threatening condition.
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BACKGROUND: Stem cell-based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small-scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. METHODS: We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. RESULTS: We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT-related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. CONCLUSIONS: Standardization plays an important role in the sustained, rapid and healthy development of SCT.
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Transplante de Células-Tronco , Humanos , Padrões de ReferênciaRESUMO
In Vehicular Edge Computing Network (VECN) scenarios, the mobility of vehicles causes the uncertainty of channel state information, which makes it difficult to guarantee the Quality of Service (QoS) in the process of computation offloading and the resource allocation of a Vehicular Edge Computing Server (VECS). A multi-user computation offloading and resource allocation optimization model and a computation offloading and resource allocation algorithm based on the Deep Deterministic Policy Gradient (DDPG) are proposed to address this problem. Firstly, the problem is modeled as a Mixed Integer Nonlinear Programming (MINLP) problem according to the optimization objective of minimizing the total system delay. Then, in response to the large state space and the coexistence of discrete and continuous variables in the action space, a reinforcement learning algorithm based on DDPG is proposed. Finally, the proposed method is used to solve the problem and compared with the other three benchmark schemes. Compared with the baseline algorithms, the proposed scheme can effectively select the task offloading mode and reasonably allocate VECS computing resources, ensure the QoS of task execution, and have a certain stability and scalability. Simulation results show that the total completion time of the proposed scheme can be reduced by 24-29% compared with the existing state-of-the-art techniques.
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PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a dominant pathological type in China. NUPR1 is a complex molecule implicated in various physiological and biological functions whose expression is upregulated in response to stress. Furthermore, autophagy is a vital physiological mechanism in the onset and metastasis of malignancies. This study aims to uncover the influence of NUPR1 on ESCC occurrence and development by regulating autophagy while also exploring its association with the MAPK signaling pathway. METHODS: First, the differences in NUPR1 between ESCC and normal tissues were analyzed through online databases. Subsequently, the pathological tissues of clinical samples were stained and scored using immunohistochemistry. And NUPR1 expression in ESCC cells was investigated, as was the function of NUPR1 in the modulation of ESCC's malignant behavior. Furthermore, a nude mouse ESCC xenograft model was developed. Finally, RNA sequencing was performed on NUPR1-downregulated ESCC cells, which was verified using WB. RESULTS: Our findings initially uncovered differences in the expression of NUPR1 in ESCC and normal tissues. In vitro experiments demonstrated that NUPR1 downregulation significantly inhibited ESCC cell proliferation, invasion, and migration, as well as promoted their apoptosis. Our xenograft model exhibited significant inhibition of ESCC tumors upon NUPR1 downregulation. Subsequently, RNA sequencing uncovered that NUPR1 regulates its malignant biological behavior through MAPK-mTOR signaling pathway. Finally, we found that NUPR1 downregulation can inhibit autophagic flux in ESCC. CONCLUSION: Collectively, our findings show that NUPR1 enhances the progression of ESCC by triggering autophagy and is associated with the MAPK-mTOR signaling pathway.
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Autofagia , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Camundongos Nus , Proteínas de Neoplasias , Serina-Treonina Quinases TOR , Humanos , Autofagia/fisiologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Camundongos , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proliferação de Células/fisiologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/fisiologia , Masculino , Feminino , Apoptose/fisiologia , Camundongos Endogâmicos BALB C , Movimento CelularRESUMO
BACKGROUND: The molecular features of fibroblasts and the role of fibrosis in neoadjuvant chemotherapy (NAC) response and breast cancer (BRCA) prognosis remain unclear. Therefore, this study aimed to investigate the impact of interstitial fibrosis on the response and prognosis of patients with BRCA undergoing NAC treatment. MATERIALS AND METHODS: The molecular characteristics of pathologic complete response (pCR) and non-pCR (npCR) in patients with BRCA were analyzed using multiomics analysis. A clinical cohort was collected to investigate the predictive value of fibrosis in patients with BRCA. RESULTS: Fibrosis-related signaling pathways were significantly upregulated in patients with npCR. npCR may be associated with distinct and highly active fibroblast subtypes. Patients with high fibrosis had lower pCR rates. The fibrosis-dependent nomogram for pCR showed efficient predictive ability [training set: area under the curve [AUC]=0.871, validation set: AUC=0.792]. Patients with low fibrosis had a significantly better prognosis than those with high fibrosis, and those with a high fibrotic focus index had significantly shorter overall and recurrence-free survival. Therefore, fibrosis can be used to predict pCR. Our findings provide a basis for decision-making in the treatment of BRCA. CONCLUSIONS: npCR is associated with a distinct and highly active fibroblast subtype. Furthermore, patients with high fibrosis have lower pCR rates and shorter long-term survival. Therefore, fibrosis can predict pCR. A nomogram that includes fibrosis can provide a basis for decision-making in the treatment of BRCA.
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Neoplasias da Mama , Fibrose , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Prognóstico , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Adulto , Quimioterapia Adjuvante , NomogramasRESUMO
BACKGROUND: Aberrant expression of MUC1 correlates with the progression of esophageal squamous cell carcinoma (ESCC), this study aimed to explore the effect of targeting MUC1 by Go-203 on malignant behavior of ESCC and the underlying mechanism. METHODS AND RESULTS: IHC was used to examine the expression of MUC1 and DNAJB6 in ESCC samples. qRT-PCR and western blotting were used to examine the expression of MUC1 and DNAJB6 in ESCC cell lines. CCK8, wound healing, and transwell assays were used to determine the effect of regulating MUC1/DNAJB6 on the proliferation, migration, and invasion of ESCC cells. The effect of overexpressing/targeting MUC1 on the activation of the AKT/HSF-1 pathway was determined by western blotting. A negative correlation was confirmed between the expression of DNAJB6 and MUC1 in ESCC tissue samples by IHC, and high expression of MUC1 and low expression of DNAJB6 correlated with lymph node metastasis in ESCC patients. Overexpressing MUC1 downregulated the expression of DNAJB6, promoted ESCC proliferation, invasion, migration and activated the AKT pathway, while targeting MUC1 suppressed proliferation, invasion, migration, and the AKT pathway and up-regulated DNAJB6 expression in vitro. Moreover, MUC1 increased the phosphorylation of HSF-1 via the AKT pathway, and inhibiting AKT-HSF-1 increased the expression of DNAJB6 in vitro. CONCLUSIONS: This study indicated that MUC1 could promote tumorigenesis and metastasis in ESCC by downregulating DNAJB6 expression through AKT-HSF-1 pathway.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/metabolismo , Metástase Linfática , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Mucina-1/metabolismoRESUMO
SCOPE: Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared. METHODS AND RESULTS: Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids. CONCLUSION: Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.
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Colesterol , Glucose , Masculino , Animais , Camundongos , Azeite de Oliva/farmacologia , Óleo de Brassica napus , Glucose/metabolismo , Metabolismo dos Lipídeos , Transcriptoma , Camundongos Endogâmicos C57BL , Gorduras na Dieta , Fígado/metabolismo , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Mirísticos/metabolismo , Óleos de Plantas/farmacologia , Ácidos Graxos/metabolismoRESUMO
In the past few decades, many researchers believed that a high-fat and high-calorie diet is the most critical factor leading to metabolic diseases. However, increasing evidence shows a high-carbohydrate and low-fat diet may also be a significant risk factor. It needs a comprehensive evaluation to prove which viewpoint is more persuasive. We systematically compared the effects of high-fat and high-calorie diets and high-carbohydrate and low-fat ones on glycolipid metabolism in mice to evaluate and compare the effects of different dietary patterns on metabolic changes in mice. Sixty 8-week-old male C57BL/6 mice were divided into four groups after acclimatization and 15% (F-15), 25% (F-25), 35% (F-35), and 45% (F-45) of their dietary energy was derived from fat for 24 weeks. The body weight, body-fat percentage, fasting blood glucose, lipid content in the serum, and triglyceride content in the livers of mice showed a significantly positive correlation with dietary oil supplementation. Interestingly, the total cholesterol content in the livers of mice in the F-15 group was significantly higher than that in other groups (p < 0.05). Compared with the F-45 group, the mRNA expression of sterol synthesis and absorption-related genes (e.g., Asgr1, mTorc1, Ucp20, Srebp2, Hmgcr, and Ldlr), liver fibrosis-related genes (e.g., Col4a1 and Adamts1) and inflammation-related genes (e.g., Il-1ß and Il-6) were significantly higher in the F-15 group. Compared with the F-45 group, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was decreased in the F-15 group. While unclassified_f_Lachnospiraceae and Akkermansia are potentially beneficial bacteria, they have the ability to produce short-chain fatty acids and modulate cholesterol metabolism. In addition, the relative abundance of unclassified_f_Lachnospiraceae and Akkermansia was significantly positively correlated with fatty acid transporters expression and negatively correlated with that of cholesteryl acyltransferase 1 and cholesterol synthesis-related genes. In conclusion, our study delineated how a high-fat and high-calorie diet (fat supplied higher than or equal to 35%) induced obesity and hepatic lipid deposition in mice. Although the high-carbohydrate and low-fat diet did not cause weight gain in mice, it induced cholesterol deposition in the liver. The mechanism is mainly through the induction of endogenous synthesis of cholesterol in mice liver through the ASGR1-mTORC1-USP20-HMGCR signaling pathway. The appropriate oil and carbon water ratio (dietary energy supply from fat of 25%) showed the best gluco-lipid metabolic homeostasis in mice.
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Dieta Hiperlipídica , Fígado , Masculino , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Colesterol/metabolismo , Metabolismo dos Lipídeos , Carboidratos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismoRESUMO
Subacute mycotoxin exposure in food is commonly overlooked. As one of the most toxic trichothecene mycotoxins, the T-2 toxin severely pollutes human foods and animal feeds. In our study, we investigated the effects of low-dose T-2 toxin on glucose and lipid metabolic function and further investigated the protective effect of tannic acid (TA) in C57BL/6J mice. Results showed that low-dose T-2 toxin significantly impaired blood glucose and lipid homeostasis, promoted ferroptosis in the pancreas and subsequent repression of insulin secretion in ß-cells, and impacted hepatic glucose and lipid metabolism by targeted inhibition of the insulin receptor substrate (IRS)/phosphatidylin-ositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which induced insulin resistance and steatosis in the liver. TA treatment attenuated pancreatic function and hepatic metabolism by ameliorating oxidative stress and insulin resistance in mice. These findings provide new perspectives on the toxic mechanism and intervention of chronic subacute toxicity of foodborne mycotoxins.
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Resistência à Insulina , Toxina T-2 , Humanos , Animais , Camundongos , Glucose/metabolismo , Toxina T-2/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Metabolismo dos Lipídeos , Lipídeos/farmacologia , Insulina/metabolismoRESUMO
The effects of dietary supplementation with two particle sizes of nano zinc oxide (ZnO) on growth performance, immune function, intestinal morphology, and the gut microbiome were determined in a 42-day broiler chicken feeding experiment. A total of 75 one-day-old Arbor Acres broilers were randomized and divided into three groups with five replicates of five chicks each, including the conventional ZnO group (NC), the nano-ZnO group with an average particle size of 82 nm (ZNPL), and the nano-ZnO group with an average particle size of 21 nm (ZNPS). Each group was supplemented with 40 mg/kg of ZnO or nano-ZnO. Our results revealed that birds in the ZNPS group had a higher average daily gain and a lower feed-to-gain ratio than those in the NC group. ZNPS significantly increased the thymus index and spleen index, as well as the levels of serum metallothionein (MT), superoxide dismutase (SOD), and lysozyme (LZM). The ZNPS treatments reduced interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α) levels and increased IL-2 and interferon (IFN)-γ levels compared to that in the NC group. Additionally, compared with the birds in the NC group, those in the nano-ZnO group had a higher villus height to crypt depth ratio of the duodenum, jejunum, and ileum. Bacteroides increased in the ZNPS group at the genus level. Further, unidentified_Lachnospiraceae, Blautia, Lachnoclostridium, unidentified_Erysipelotrichaceae, and Intestinimonas were significantly increased in the ZNPL group. In conclusion, nano-ZnO improved the growth performance, promoted the development of immune organs, increased nonspecific immunity, improved the villus height to crypt depth ratio of the small intestine, and enriched the abundance of beneficial bacteria. Notably, the smaller particle size (21 nm) of nano-ZnO exhibited a more potent effect.
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BACKGROUND: Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). METHODS: A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. RESULTS: A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. CONCLUSIONS: Transplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Incidência , Sobrevivência de Enxerto , Fígado , Doadores de Tecidos , Transplante de Fígado/métodos , Estudos Retrospectivos , Morte , Morte EncefálicaRESUMO
Dark tea is a fermented tea that plays a role in regulating the homeostasis of intestinal microorganisms. Previous studies have found that dark tea can improve obesity and has a lipid-lowering effect. In this study, green tea, Ilex latifolia Thunb (kuding tea) and Momordica grosvenori (Luo Han Guo) were added to a new compound dark tea (CDT), to improve the taste and health of this beverage. High-fat diet-fed C57BL/6J mice were treated with low- (6 mg/mL) or high- (12 mg/mL) concentrations of CDT for 18 weeks to assess their effect on lipid metabolism. Our results suggest that low- and high-concentrations of CDT could reduce body weight by 15 and 16% and by 44 and 38% of body fat, respectively, by attenuating body weight gain and fat accumulation, improving glucose tolerance, alleviating metabolic endotoxemia, and regulating the mRNA expression levels of lipid metabolism-related genes. In addition, low concentrations of CDT were able to reduce the abundance of Desulfovibrio, which is positively associated with obesity, and increase the abundance of Ruminococcus, which are negatively associated with obesity. This study demonstrates the effect of CDT on ameliorating lipid metabolism and provides new insights into the research and development of functional tea beverages.
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The aim of this study was to evaluate the effects of anti-stress agents on the growth performance and immune function of broilers under immune stress conditions induced by vaccination. A total of 128, 1-day-old Arbor Acres broilers were randomly divided into four groups. Group normal control (NC) was the control group. Group vaccination control (VC), T 0.5%, and T 1% were the treatment groups, which were nasally vaccinated with two doses of the Newcastle disease virus (NDV) vaccine. The chicks in groups T 0.5% and T 1% were fed conventional diets containing 0.5% and 1% anti-stress agents. Thereafter, these broilers were slaughtered on 1, 7, 14, and 21 days post-vaccination. The results indicated that anti-stress agents could significantly reduce serum adrenocorticotropic hormone (ACTH) (P < 0.01) and cortisol (CORT) (P < 0.05) levels, and improve the growth performance (P < 0.05) and immune function of broilers (P < 0.05); However, the levels of malondialdehyde (MDA) (P < 0.05) were decreased, and the decreased total antioxidant capacity (T-AOC) (P < 0.01) levels mediated by vaccination were markedly improved. In addition, anti-stress agents could attenuate apoptosis in spleen lymphocytes (P < 0.01) by upregulating the ratio of Bcl-2 to BAX (P < 0.01) and downregulating the expression of caspase-3 and -9 (P < 0.01), which might be attributed to the inhibition of the enzymatic activities of caspase-3 and -9 (P < 0.05). In conclusion, anti-stress agents may improve growth performance and immune function in broilers under immune-stress conditions.RESEARCH HIGHLIGHTS Investigation of effects and mechanism of immune stress induced by vaccination.Beneficial effect of anti-stress agents on growth performance, immune function, oxidative stress, and regulation of lymphocyte apoptosis.Demonstration of the effects of apoptosis on immune function in the organism.
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Antioxidantes , Galinhas , Animais , Caspase 3/metabolismo , Antioxidantes/metabolismo , Dieta/veterinária , Vacinação/veterinária , Imunidade , Ração Animal/análise , Suplementos NutricionaisRESUMO
Introducing partial task offloading into vehicle edge computing networks (VECNs) can ease the burden placed on the Internet of Vehicles (IoV) by emerging vehicle applications and services. In this circumstance, the task offloading ratio and the resource allocation of edge servers (ES) need to be addressed urgently. Based on this, we propose a best response-based centralized multi-TaV computation resource allocation algorithm (BR-CMCRA) by jointly considering service vehicle (SeV) selection, offloading strategy making, and computing resource allocation in a multiple task vehicle (TaV) system, and the utility function is related to the processing delay of all tasks, which ensures the TaVs's quality of services (QoS). In the scheme, SeV is first selected from three candidate SeVs (CSVs) near the corresponding TaV based on the channel gain. Then, an exact potential game (EPG) is conducted to allocate computation resources, where the computing resources can be allocated step by step to achieve the maximum benefit. After the resource allocation, the task offloading ratio can be acquired accordingly. Simulation results show that the proposed algorithm has better performance than other basic algorithms.
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In the biomedical field, polyurethane (PU) is widely used in interventional catheters, artificial hearts, artificial blood vessels, orthopedic materials, medical adhesives, and other medical devices. In this paper, a method based on machine vision was proposed to control the drafting and winding accuracy of PU filament in order to solve the problem of centrifugal runout when the mold rotates. The centrifugal runout of the mold directly affected the preparation efficiency and quality of long artificial blood vessel by wet spinning. Through non-contact real-time detection of the filament diameter and the angle between the axis of filament and the axis of mold, the motion parameters of the two motors driving the moving platform and the drafting roller could be adjusted in real time to achieve the purpose of online real-time control of filament drafting and winding accuracy. The vision control method proposed in this paper was used to carry out the PU tube preparation experiment. The visual measurement results of the filament diameter and the included angle were compared with the manual measurement results. The average value of the diameter error is 0.0096mm, and the average value of winding angle is 0.4777°. The results proved the accuracy of the visual measuring method and testified it feasible to using machine vision instead of manual method to detect filament diameter and winding angle. Properties of the prepared PU tube were tested and analyzed. The filament diameter measured by the 3D microscope was about 0.87 mm and significantly smaller than the filament diameter before winding. This indicated that the winding was uniform, the extrusion was tight, and the adhesion was good.
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The tripartite motif (TRIM) family proteins exhibit oncogenic or anti-oncogenic roles in various cancers. As a TRIM family member, TRIM36 is expressed in lung adenocarcinoma (LUAD), but its roles remain unexplored. Here, we set to investigate the clinical relevance and the biological actions of TRIM36 in LUAD. mRNA levels of TRIM36 and the Kaplan-Meier survival analysis for patients with LUAD were analyzed from The Cancer Genome Atlas (TCGA) database. Real-time PCR and western blotting were utilized to measure TRIM36 levels both in vivo and in vitro. We demonstrated that TRIM36 levels were significantly decreased in LUAD patients. The low expression of TRIM36 was correlated with a poor prognosis. Overexpression and knock-down studies illustrated that TRIM36 inhibits cell proliferation and promotes apoptosis in LUAD cell lines. LUAD cells were irradiated with 60Co. In addition, TRIM36 enhanced radiosensitivity in LUAD cell lines. Moreover, we found that TRIM36 expression was negatively associated with RAD51. Co-overexpressing RAD51 blocked TRIM36's effects on proliferation and apoptosis. TRIM36 formed a complex with RAD51, promoting its ubiquitination. Inhibiting hsa-miR-376a-5p enhanced apoptosis and the effects were mediated by TRIM36 in response to radiation. In conclusion, our results indicated that TRIM36 is anti-oncogenic in LUAD by promoting RAD1 ubiquitination. Hsa-miR-376a-5p acts upstream of TRIM36. TRIM36 and RAD1 may serve as prognostic indicators for LUAD. The interactions between TRIM36, RAD1 and hsa-miR-376a-5p can be future therapeutic targets to increase radiation sensitivity in LUAD patients.
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Adenocarcinoma de Pulmão , Proteínas de Transporte , Neoplasias Pulmonares , MicroRNAs , Rad51 Recombinase , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Tolerância a Radiação/genética , UbiquitinaçãoRESUMO
Hydrogels, with a three-dimensional network of water-soluble polymer and water, could simulate the critical properties of extracellular matrix, which has been widely used in bone tissue engineering. However, most of conventional hydrogels for bone regeneration are fragile and have poor osteogenic activity, which restricts their applications. In this work, a novel nanoparticle-hydrogel composite consisting of physically cross-linked double-network loaded with MgO-Ag2O nanocomposites was developed by the sol-gel method. The Mg2+ released from MgO-Ag2O nanocomposites was used as an ionic cross-linking site of sodium alginate (SA), while the hydrophobic micelles in the polyacrylamide (PAAM) network is acted as another crosslinking point. The results indicated that the novel nanoparticle-hydrogel composites had good self-recovery ability and excellent mechanical properties compared with the conventional sodium alginate (SA)/polyacrylamide (PAAM) hydrogels. Additionally, it showed a slow release of Mg and Ag ions due to the dual function of the embedding effect of hydrogels and the increasing pH of the solution induced by the hydrolysis of sodium alginate. In terms of in vitro tests, the nanoparticle-hydrogel composites showed significantly stimulatory effects on the proliferation and differentiation of SaOS-2 cells. In addition, the antibacterial effects of the nanoparticle-hydrogel composites were gradually enhanced with the increase of MgO-Ag2O content.
Assuntos
Hidrogéis , Nanocompostos , Alginatos/farmacologia , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Íons/farmacologia , Óxido de Magnésio/farmacologia , Micelas , Osteogênese , Água/farmacologiaRESUMO
BACKGROUND: Fibulin-4, namely, EFEMP2, is an essential matricellular protein associated with a variety of malignancies. The aim of this study was to explore the role of fibulin-4 in the progression of esophageal squamous cell carcinoma (ESCC), as well as its effect on ESCC sensitivity to apatinib treatment. METHODS: The expression of fibulin-4 in ESCC tissues and cell lines was detected. Stably transfected ESCC cells were established by transducing lentiviral vectors for silencing or overexpressing the fibulin-4 gene into ESCC cells, and a subcutaneous xenograft tumor model of ESCC in mice was successfully established. IHC, RT-qPCR and western blotting were used to detect the expression of related genes and proteins. The CCK8 assay, EdU cell proliferation assay, wound healing assay, transwell assay and flow cytometry were used to evaluate the proliferation, invasion, migration and apoptosis of ESCC cells. After mice were sacrificed, the transplanted tumors were resected, and their volumes were measured. RESULTS: The expression of fibulin-4 was significantly increased in both ESCC tissues and cell lines, and the high expression was closely related to the poor clinicopathological features. Downregulation of fibulin-4 inhibited the proliferation, invasion and migration of ESCC cells in vitro and in vivo. Meanwhile, fibulin-4 knockdown inhibited autophagy of tumor cells by activating the Akt-mTOR signaling pathway and significantly promoted apatinib-induced apoptosis of ESCC cells. CONCLUSION: Our study showed that fibulin-4 is an oncogene that can promote ESCC progression and inhibit apoptosis. Downregulation of fibulin-4 enhances the sensitivity of ESCC cells to apatinib by inhibiting cellular protective autophagy through activating the Akt-mTOR signaling pathway.