Multi-User Computation Offloading and Resource Allocation Algorithm in a Vehicular Edge Network.

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.

Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy.

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.

NUPR1 induces autophagy and promotes the progression of Esophageal squamous cell carcinoma via the MAPK-mTOR pathway.

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.

Integrative analysis identifies molecular features of fibroblast and the significance of fibrosis on neoadjuvant chemotherapy response in breast cancer.

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 multi-omics 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.

MUC1 promotes lymph node metastasis in esophageal squamous cell carcinoma by downregulating DNAJB6 expression.

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.

High-Carbohydrate Diet Consumption Poses a More Severe Liver Cholesterol Deposition than a High-Fat and High-Calorie Diet in Mice.

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.

Metabolomic and Transcriptomic Analysis of Effects of Three MUFA-Rich Oils on Hepatic Glucose and Lipid Metabolism in Mice.

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.

Tannic Acid Ameliorates Systemic Glucose and Lipid Metabolic Impairment Induced by Low-Dose T-2 Toxin Exposure.

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.

Effect of Two Particle Sizes of Nano Zinc Oxide on Growth Performance, Immune Function, Digestive Tract Morphology, and Intestinal Microbiota Composition in Broilers.

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.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic structure.

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.

Compound dark tea ameliorates obesity and hepatic steatosis and modulates the gut microbiota in mice.

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.

Effects of anti-stress agents on the growth performance and immune function in broiler chickens with vaccination-induced stress.

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.

A Game-Based Computing Resource Allocation Scheme of Edge Server in Vehicular Edge Computing Networks Considering Diverse Task Offloading Modes.

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.

Precision control of polyurethane filament drafting and winding based on machine vision.

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.

TRIM36 enhances lung adenocarcinoma radiosensitivity and inhibits tumorigenesis through promoting RAD51 ubiquitination and antagonizing hsa-miR-376a-5p.

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.

Simultaneously stimulated osteogenesis and anti-bacteria of physically cross-linked double-network hydrogel loaded with MgO-Ag2O nanocomposites.

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.

Downregulation of fibulin-4 inhibits autophagy and promotes the sensitivity of esophageal squamous cell carcinoma cells to apatinib by activating the Akt-mTOR signaling pathway.

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.

Hypoxia-inducible factor-2α promotes EMT in esophageal squamous cell carcinoma through the Notch pathway.

BACKGROUND: Esophageal cancer is one of the most lethal tumors worldwide. The most common histological type in China is esophageal squamous cell carcinoma (ESCC), accounting for 90% of cases. Esophageal cancer occurs at a high incidence in certain areas, among which China has the highest incidence. Although various therapeutic strategies have been used in clinical treatment, the 5-year survival rate is still not satisfactory, as it is only 15-20%. The reason for the poor prognosis of ESCC is that the distant metastasis easily occurs in these tumors. However, the mechanism of metastasis has not been studied clearly. OBJECTIVES: To investigate the function of hypoxia-inducible factor-2α (hif-2α) in ESCC. MATERIAL AND METHODS: Immunohistochemistry and immunofluorescence were used to detect the expression of hif-2α in tissues and cells. Clinicopathological data from 100 ESCC patients were used to investigate the relationship between hif-2α and prognosis. Cell experiments (Cell Counting Kit-8 (CCK-8) assay and transwell migration assays) were utilized to verify the roles of hif-2α on the ESCC cells. Western blotting was used to explore the mechanism of hif-2α in ESCC. Mouse model was used to clarify the effect of hif-2α on ESCC cells in vivo. RESULTS: The hif-2α was overexpressed both in ESCC tissues and cells, and was related with poor prognosis in ESCC patients. The CCK-8 assay evidenced that silencing hif-2α suppressed the proliferation of ESCC cells, while transwell assay - that overexpression of hif-2α promoted the migration of ESCC cells. Western blot assay indicated that hif-2α regulated epithelial-mesenchymal transition (EMT) through Notch pathway in ESCC cells. Mouse model showed that silencing hif-2α significantly suppressed the proliferation of ESCC cells in vivo. CONCLUSIONS: The hif-2α promotes EMT in ESCC through the Notch pathway.

Purified diet versus whole food diet and the inconsistent results in studies using animal models.

In animal models, purified diets (PDs) and whole food diets (WFDs) are used for different purposes. In similar studies, different dietary patterns may lead to inconsistent results. The aim of this study was to evaluate and compare the effects of WFDs and PDs on changes in the metabolism of mice. We found that different dietary patterns produced different results in lipid metabolism experiments. Compared with those of the PD-fed mice, the WFD-fed mice had higher body weights and serum glucose, serum lipid, and liver lipid levels (p < 0.01), as well as low glucose tolerance (p < 0.01) and insulin sensitivity (p < 0.05). The body weight and fasting blood glucose increased by 20% in the WFD-fed mice, and the white adipose tissue weight increased by ∼50%. The WFD-fed mice also had a comparatively higher abundance of Lactobacillus, Turicibacter, Bifidobacterium, Desulfovibrio, and Candidatus saccharimonas (p < 0.01), which were positively correlated with lipid accumulation. Dietary patterns should be chosen cautiously in studies that use rodents as models. Inappropriate selection of animal dietary patterns may lead to experimental systematic errors and paradoxical results.