A novel amino acid metabolism-related gene signature to predict the overall survival of esophageal squamous cell carcinoma patients.

Background: Esophageal squamous cell carcinoma (ESCC) has a poor early detection rate, prognosis, and survival rate. Effective prognostic markers are urgently needed to assist in the prediction of ESCC treatment outcomes. There is accumulating evidence of a strong relationship between cancer cell growth and amino acid metabolism. This study aims to determine the relationship between amino acid metabolism and ESCC prognosis. Methods: This study comprehensively evaluates the association between amino acid metabolism-related gene (AAMRG) expression profiles and the prognosis of ESCC patients based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the expression of prognosis-related genes. Results: A univariate Cox regression analysis of TCGA data identified 18 prognosis-related AAMRGs. The gene expression profiles of 90 ESCC tumor and normal tissues were obtained from the GSE20347 and GSE67269 datasets. Two differently expressed genes (DEGs) were considered as ESCC prognosis-related genes; and they were branched-chain amino acid transaminase 1 (BCAT1) and methylmalonic aciduria and homocystinuria type C protein (MMACHC). These two AAMRGs were used to develop a novel AAMRG-related gene signature to predict 1- and 2-year prognostic risk in ESCC patients. Both BCAT1 and MMACHC expression were verified by RT-qPCR. A prognostic nomogram that incorporated clinical factors and BCAT1 and MMACHC gene expression was constructed, and the calibration plots showed that it had good prognostic performance. Conclusions: The AAMRG signature established in our study is efficient and could be used in clinical settings to predict the early prognosis of ESCC patients.

Identification and validation of a prognostic signature of cuproptosis-related genes for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly lethal form of cancer. Cuproptosis is a recently discovered form of regulated cell death. However, its significance in ESCC remains largely unknown. In this study, we observed significant expression differences in most of the 12 cuproptosis-related genes (CRGs) in the TCGA-ESCC dataset, which was validated using GSE20347, GSE38129, and individual ESCC datasets. We were able to divide patients in the TCGA-ESCC cohort into two subgroups based on disease, and found significant differences in survivor outcomes and biological functions between these subgroups. Additionally, we identified 11 prognosis-related genes from the 12 CRGs using LASSO COX regression analysis and constructed a CRGs signature for ESCC. Patients were categorized into high- and low-risk subgroups based on their median risk score, with those in the high-risk subgroup having significantly worse overall survival than those in the low-risk subgroup. The CRGs signature was also highly accurate in predicting prognosis and survival outcomes. Univariate and multivariate Cox regression analyses revealed that 8 of the 11 CRGs were independent prognostic factors for predicting survival in ESCC patients. Furthermore, our nomogram performed well and could serve as a useful tool for predicting prognosis. Finally, our risk model was found to be relevant to the sensitivity of targeted agents and immune infiltration. Functional enrichment analysis demonstrated that the risk model was associated with biological pathways of tumor migration and invasion. In summary, our study may provide a promising prognostic signature based on CRGs and offers potential targets for personalized therapy.

Will cultured meat be served on Chinese tables? A study of consumer attitudes and intentions about cultured meat in China.

This research investigates the attitudes and intentions of Chinese consumers about cultured "meat" (CM). We also investigate framing effects through the names used for these products ("cultured meat," "artificial meat," and "cell-based meat") and the effect of information provision. Of the 1532 consumers in our sample, most had not heard of "cultured meat" or "cell-based meat" before, although 70% had heard of "artificial meat". Around 44% of the participants indicated that they would be willing to try CM, and 32% would be likely to purchase it. Participants disliked the terms "cultured meat" and "cell-based meat" less than they disliked the term "artificial meat," although the latter was the most familiar to them. The provision of neutral information on the production process increased consumer support for CM, but the effect was limited. Prior knowledge and naming terms were strong predictors of attitudes and willingness to buy. A key implication is that stakeholders should cautiously apply framing strategies when introducing CM to the public.

CPT2 downregulation triggers stemness and oxaliplatin resistance in colorectal cancer via activating the ROS/Wnt/ß-catenin-induced glycolytic metabolism.

Carnitine palmitoyltransferase 2 (CPT2) has been demonstrated to act as a tumor promotor or suppressor in different types of cancers. However, little is known about the effect of CPT2 on colorectal cancer (CRC). In the present study, we analyzed CPT2 expression in CRC tissues and cells. CPT2 was overexpressed in CRC cell lines (SW480 and RKO), and its effects and molecular mechanism on the proliferation, glycolysis, stemness, and oxaliplatin sensitivity were investigated. The xenograft experiment was used to confirm the influence of CPT2 on CRC tumorigenesis in vivo. We found that CPT2 expression was significantly downregulated in CRC patients, and its lower expression was associated with the poor prognosis, large tumor size, advanced TNM stage, and poor histological grade differentiation of patients. Upregulation of CPT2 significantly inhibited the proliferation, glycolytic metabolism, cancer stem cell properties, and oxaliplatin resistance in CRC cells. Also, the increase of CPT2 inhibited tumorigenesis, stemness and glycolysis, while enhanced oxaliplatin sensitivity in mouse models. Mechanistically, CPT2 functioned via suppressing the activation of Wnt/ß-catenin pathway through repressing ROS production. In conclusion, our results demonstrated that CPT2 was decreased in CRC, and CPT2 downregulation could trigger stemness and oxaliplatin resistance in CRC via activating the ROS/Wnt/ß-catenin-induced glycolytic metabolism. This study indicates that CPT2 is a potential therapeutic target for CRC.

Propofol combined with remifentanil reduces the adverse reactions of patients undergoing laparoscopic cholecystectomies.

OBJECTIVE: To explore the effectiveness of using isoflurane and propofol combined with remifentanil in laparoscopic cholecystectomies (LC). METHODS: A total of 118 patients undergoing LC in our hospital from April 2018 to January 2019 were recruited as the study cohort. 56 of the patients were anesthetized with isoflurane combined with remifentanil during their operations (the IR group), and the other 62 patients were anesthetized with propofol combined with remifentanil during their operations (the PR group). The effects of the two anesthesia methods on the hemodynamics and stress responses were compared, and the postoperative recoveries, adverse reactions, analgesia, and cognitive functions were recorded. RESULTS: Compared with the IR group, the average arterial pressure, heart rate, norepinephrine, and cortisol decreased in the PR group. Compared with the IR group, the total postoperative adverse reaction rate was lower in the PR group. Compared with the IR group, the spontaneous respiration recovery times, the times to opening eyes, and the extubation times were significantly shortened in the PR group. There was no significant difference in the postoperative pain levels between the two groups. Compared with the IR group, the postoperative cognitive function assessment was better in the PR group. CONCLUSION: Compared with isoflurane combined with remifentanil, propofol combined with remifentanil has a smaller impact on the hemodynamics and cognitive functions of patients undergoing LC, and it causes a more significant reduction in the stress response. In addition, its postoperative adverse reactions are lower, so it is worthy of promoting in clinical practice.

Stereotactic body radiotherapy versus radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy and safety of stereotactic body radiotherapy (SBRT) with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, MedLine, EMBASE, the Cochrane Library and Web of Science were searched to identify potentially eligible studies comparing the efficacy and safety of SBRT with RFA for HCC from January 1990 to May 2020. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the effect size for overall survival (OS), local control (LC) and complications. RESULTS: Seven studies including 7928 patients were enrolled in this meta-analysis. The results showed that SBRT was not inferior to RFA based on the pooled HR for OS (HR = 1.09, 95%CI = 0.78-1.52, p = .62); however, the pooled HR for the LC rate showed the superiority of SBRT (HR = 0.54, 95%CI = 0.35-0.84, p = .006). Subgroup analysis showed that the pooled HR for the LC rate favored SBRT in patients with tumors sized >2 cm (HR = 0.41, 95%CI = 0.23-0.74, p = .003), but no significant difference was observed in patients with tumors sized ≤2 cm (HR = 0.56, 95%CI = 0.25-1.28, p = .17). In addition, no significant differences in the incidence of late severe complications were observed between the SBRT and RFA groups (OR = 1.01, 95%CI = 0.59-1.73, p = .97). CONCLUSIONS: Based on the current data, we concluded that SBRT was well tolerated with an OS equivalent to that with RFA; SBRT was superior to RFA in terms of LC of HCC, especially in those with tumors sized >2 cm.

Numerical Analysis of Fluid Flow and Heat Transfer in Micro-Channel Heat Sinks with Double-Layered Complex Structure.

Micro-channel heat sink (MCHS) has been extensively used in various electronic cooling fields. Double-layered MCHS, or DL-MCHS, is regarded as one effective technique for high-heat-flux transfer and is expected to meet the ever-increasing heat load requirement of future electronic device generations. In order to improve the cooling capacity, two new types of the MCHS, with a double-layered matrix structure (DL-M) and double-layered interlinked matrix structure (DL-IM) are proposed and investigated numerically. The two designs are compared with the traditional double-layered rectangular structure (DL-R) and the double-layered triangular structure (DL-T). Different properties of the heat sink are investigated to assess the overall heat transfer performance, for which coolant flow and heat transfer are both evaluated. The numerical results reveal that the periodical slot subchannel in the matrix has a significant effect on fluid flow for heat transfer. In comparison to the DL-R and the DL-T, the DL-M and DL-IM realize a much lower pressure drop and temperature rise at the base surface and also have higher Nusselt number and secondary flow intensity, therefore, manifesting better overall thermal performance. In the DL-M and DL-IM, the coolant flows along the periodical subchannel in one layer and is redirected into the second layer with vortices being induced. The vortices promote the coolant mixing and enhance the mass and heat transfer. These geometric design strategies can provide references for wide heat sink applications.

Peptides of tetraspanin oncoprotein CD151 trigger active immunity against primary tumour and experimental lung metastasis.

BACKGROUND: Active immunotherapy is an effective, long-lasting, cheap, and safe approach to suppress cancer progression; however, the key issue is to develop appropriate tumour vaccines. Oncoproteins are up-regulated under various stress conditions and promote cell survival. Oncoproteins and their immunogenic domains could serve well as tumour vaccines and prime the hosts' active anti-tumour immunity. METHODS: Proteomic and bioinformatic analyses were performed to identify potential tumour associated antigens (TAAs). Then, peptides derived from CD151 were designed and synthesized according to the major histocompatibility complex (MHC) I binding and immunogenicity. Cytotoxicity assay, flow cytometry, immunohistochemistry, and in vivo bioluminescence imaging were performed to assess the active anti-tumour immunity triggered by CD151 peptides in H22 primary hepatoma and experimental 4T1 breast cancer lung metastasis models. FINDINGS: CD151 was identified as an ideal TAA based on proteomic and bioinformatic analyses. CD151 peptides as tumour vaccines triggered active anti-tumour immunity against H22 hepatoma and the lung metastasis of 4T1 breast cancer in two mouse models through the activation of CD8+IFNγ+ lymphocytes and the subsequent targeted cytotoxicity. Further, the peptides suppressed the negative regulators, myeloid-derived suppressor cells. Survival was prolonged for mice with lung metastases from CD151 peptide-immunised groups. INTERPRETATION: The up-regulated oncoproteins in 8 Gy-irradiated tumour cells are good candidates for designing immunogenic peptides as tumour vaccines. Anti-tumour active immunity primed by peptides from CD151 may be an effective and safe approach to suppress cancer progression.

EGFLAM correlates with cell proliferation, migration, invasion and poor prognosis in glioblastoma.

EGFLAM as a novel gene biomarker has been reported in some cancers but not glioblastoma (GBM) yet. To clarify the functional role of EGFLAM in GBM, we performed this study. Firstly, based on TCGA and Oncomine database, EGFLAM expression and clinical significance in GBM patients was analyzed. Furthermore, the biological effect of EGFLAM in GBM cells was determined by qRT-PCR, CCK-8 assay, colony formation assay, wound healing assay, transwell assays and western blot analysis. The databases analysis showed that EGFLAM expression was at higher levels in GBM patients with poor prognosis. The results indicated that EGFLAM silence inhibited the proliferation, migration and invasion of U87 cells, which was regulated through repression of PI3K/AKT pathway. Accordingly, the data from our work shed some light on EGFLAM might be a prognostic biomarker and therapeutic target for GBM.

Fibrinogen­like­protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis.

The protective role of fibrinogen­like­protein 1 (FGL1) in liver injury has been reported previously. However, there are few studies on FGL1 expression in gastric cancer (GC) tissues, and the role of FGL1 in GC remains unclear. The aim of the present study was to investigate the correlation between FGL1 expression and prognosis in GC patients. Data was downloaded from The Cancer Genome Atlas database, and 50 pairs of GC tissues and the corresponding non­tumor tissues were collected between 2008 to 2011. Furthermore, FGL1 expression was silenced in order to explore its role in SGC­7901 cell proliferation, invasion and migration using Cell Counting Kit­8, wound healing, Transwell invasion and migration assays, respectively. Finally, whether FGL1 is involved in epithelial­mesenchymal transition (EMT) regulation in SGC­7901 cells was determined by western blotting. The results revealed that FGL1 expression was upregulated in GC tissues, and the overall survival time of GC patients with high FGL1 expression levels was markedly shorter than that of GC patients with low FGL1 expression levels (P=0.005). In addition, silencing FGL1 significantly inhibited SGC­7901 cell proliferation, invasion and migration in vitro. Finally, western blot analyses indicated that knockdown of FGL1 markedly increased E­cadherin expression levels (P<0.01), and significantly decreased N­cadherin (P<0.01) and vimentin expression levels (P<0.01), thereby suggesting that FGL1 may promote EMT. These results indicated that FGL1 has the potential to be a predictor in GC patients as well as a target for the treatment of GC.

Effect of reactions in small eddies on biomass gasification with eddy dissipation concept - Sub-grid scale reaction model.

Large-eddy simulation (LES) approach is used for gas turbulence, and eddy dissipation concept (EDC)-sub-grid scale (SGS) reaction model is employed for reactions in small eddies. The simulated gas molar fractions are in better agreement with experimental data with EDC-SGS reaction model. The effect of reactions in small eddies on biomass gasification is emphatically analyzed with EDC-SGS reaction model. The distributions of the SGS reaction rates which represent the reactions in small eddies with particles concentration and temperature are analyzed. The distributions of SGS reaction rates have the similar trend with those of total reactions rates and the values account for about 15% of the total reactions rates. The heterogeneous reaction rates with EDC-SGS reaction model are also improved during the biomass gasification process in bubbling fluidized bed.

Multimodality Treatment May Improve the Survival Rate of Patients with Metastatic Nasopharyngeal Carcinoma with Good Performance Status.

The aim of the present study was to evaluate the benefit of chemotherapy, combined with palliative radiotherapy (PRT) and other local treatments to the metastatic sites, for patients with metastatic nasopharyngeal carcinoma (NPC) who had a performance status 0-2. We conducted a retrospective review of available data from 197 biopsy-proven NPC patients who developed metastasis after their initial definitive treatment. These patients were grouped into three categories according to the different treatment paths that were followed: the best supportive care (64 patients), chemotherapy alone (55 patients), and multimodality treatment with chemotherapy combined with PRT and other local treatments to metastatic sites (78 patients). The 2-year metastatic survival rate of patients in the multimodality treatment group was 57.7%, which was significantly better than that of the patients in both the chemotherapy alone group and the best supportive care group (32.7% and 1.6%, respectively). The independent significant factors affecting survival were the disease-free interval prior to the detection of metastatic disease, the number of metastases, the number of chemotherapy cycles and the biological effective dose of PRT. In conclusion, multimodality treatment may improve survival of select patients with recurrent NPC with distant metastases.

[Prognostic analysis of nasopharyngeal carcinoma patients with distant metastasis after curative radiotherapy].

OBJECTIVE: To analyze the prognosis and its influencing factors for nasopharyngeal carcinoma patients with distant metastasis after radical radiotherapy. METHODS: Clinical data of 184 cases of nasopharyngeal carcinoma after radical radiotherapy with distant metastases were retrospectively reviewed and the factors affecting prognosis were analyzed. RESULTS: The median survival time was 12 months for the whole group, and the 1-, 2-, and 3-year survival rates were 50.6%, 30.7% and 20.9%, respectively. Cox univariate analysis showed that the prognosis of patients with metastasis after radiotherapy was significantly related with The N stage, chemotherapy, time interval between the end of radiotherapy and occurrence of distant metastasis, metastatic sites, chemotherapy after metastasis, cycles of chemotherapy and palliative radiotherapy after metastasis (P<0.05), but not significantly related with sex, age, T stage, clinical stage, cycles of chemotherapy, radiation technique and radiation dose for initial treatment (P>0.05). Advanced N stage, no chemotherapy, short time interval between the end of radiotherapy and occurrence of distant metastasis, multiple metastases, no radiotherapy or chemotherapy for metastases were predictive for poor prognosis (P<0.05). Multivariable analysis indicated that factors including N stage at initial diagnosis, metastatic sites, whether or not chemotherapy was given, the time interval between the end of radiotherapy and the occurrence of distant metastasis were independent factors affecting the prognosis of nasopharyngeal carcinoma patients with distant metastasis after radiotherapy. CONCLUSIONS: N stage at initial diagnosis, metastatic sites, whether or not chemotherapy was given, the time interval between the end of radiotherapy and the occurrence of distant metastasis are independent factors affecting the prognosis for nasopharyngeal carcinoma patients with distant metastasis after radiotherapy. Systemic chemotherapy and local palliative radiotherapy are the primary treatment for nasopharyngeal carcinoma patients with metastasis.