Influence of nitrogen sources on wastewater treatment performance by filamentous algae in constructed wetland system.

Although filamentous algae have the characteristics of high nutrient assimilation ability, and adaptation to different conditions, studies on their role in water purification of constructed wetlands (CWs) are limited. In this study, the wastewater treatment capacity under different nitrogen sources was explored by constructing a filamentous algal CW (FACW) system. Results confirmed the fast and stable operation efficiency of the FACW system. Ammonia nitrogen was preferred in Cladophora sp. absorption and assimilation. The nutrient consumption rate (NCR) for total nitrogen (TN) of AG was 2.65 mg g-1 d-1, much higher than that of nitrate nitrogen (NG) (0.89 mg g-1 d-1). The symbiosis of bacteria and Cladophora sp. Contributed to pollutant removal. A stable and diverse community of microorganisms was found on Cladophora sp. Surface, which revealed different phylogenetic relationships and functional bacterial proportions with those attached on sediment surface. In addition, temperature and light intensity have great influence on the purification ability of plants, and low hydraulic retention time is beneficial to the cost-effective operation of the system. This study provides a method to expand the utilization of wetland plants and apply large filamentous algae to the purification of wetland water quality.

Comprehensive Analysis Based on the Cancer Immunotherapy and Immune Activation of Gastric Cancer Patients.

When it comes to aggressiveness and prognosis, immune cells play an important role in the microenvironment of gastric cancer (GC). Currently, there is no well-established evidence that immune status typing is reliable as a prognostic tool for gastric cancer. This study aimed to develop a genetic signature based on immune status typing for the stratification of gastric cancer risk. TCGA data were used for gene expression and clinical characteristics analysis. A ssGSEA algorithm was applied to type the gastric cancer cohorts. A multivariate and univariate Cox regression and a lasso regression were conducted to determine which genes are associated with gastric cancer prognosis. Finally, we were able to produce a 6-gene prognostic prediction model using immune-related genes. Further analysis revealed that the prognostic prediction model is closely related to the prognosis of patients with GC. Nomograms incorporating genetic signatures and risk factors produced better calibration results. The relationship between the risk score and gastric cancer T stage was also significantly correlated with multiple immune markers related to specific immune cell subsets. According to these results, patients' outcomes and tumor immune cell infiltration correlate with risk scores. In addition, immune cellular-based genetic signatures can contribute to improved risk stratification for gastric cancer. Clinical decisions regarding immunotherapy and followup can be guided by these features.

Identification of glycogene signature as a tool to predict the clinical outcome and immunotherapy response in breast cancer.

Background: Breast cancer is one of the most important diseases in women around the world. Glycosylation modification correlates with carcinogenesis and roles of glycogenes in the clinical outcome and immune microenvironment of breast cancer are unclear. Methods: A total of 1297 breast cancer and normal cases in the TCGA and GTEx databases were enrolled and the transcriptional and survival information were extracted to identify prognostic glycogenes using Univariate Cox, LASSO regression, Multivariate Cox analyses and Kaplan-Meier method. The immune infiltration pattern was explored by the single sample gene set enrichment method. The HLA and immune checkpoint genes expression were also compared in different risk groups. The expressions of a glycogene MGAT5 as well as its products were validated by immunohistochemistry and western blotting in breast cancer tissues and cells. Results: A 19-glycogene signature was identified to separate breast cancer patients into high- and low-risk groups with distinct overall survival rates (P < 0.001). Compared with the high-risk group, proportion of naive B cells, plasma cells and CD8+ T cells increased in the low-risk group (P < 0.001). Besides, expressions of HLA and checkpoint genes, such as CD274, CTLA4, LAG3 and TIGIT3, were upregulated in low-risk group. Additionally, highly expressed MGAT5 was validated in breast cancer tissues and cells. Downstream glycosylation products of MGAT5 were all increased in breast cancer. Conclusions: We identified a 19-glycogene signature for risk prediction of breast cancer patients. Patients in the low-risk group demonstrated a higher immune infiltration and better immunotherapy response. The validation of MGAT5 protein suggests a probable pathway and target for the development and treatment of breast cancer.

Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells.

Small extracellular vesicles (sEVs) are a type of membrane structure secreted by cells, which are involved in physiological and pathological processes by participating in intercellular communication. Glycosphingolipids (GSLs) are enriched in sEV and can be delivered to recipient cells. In this study, we found that overexpression of B3GALT4, the glycosyltransferase responsible for ganglioside GM1 synthesis, can induce the epithelial-mesenchymal transition (EMT) process in MCF-10A cells. Moreover, GM1 was verified to be presented on sEV from breast cancer cells. Overexpression of B3GALT4 resulted in elevated vesicular GM1 levels and increased sEV secretion in breast cancer cells. Proteomic analysis revealed that eleven sEV secretion-related proteins were differentially expressed, which might contribute to the altered sEV secretion. Of the identified proteins, 15 oncogenic differentially expressed proteins were documented to be presented in sEV. With the treatment of GM1-enriched sEV from breast cancer cells, the EMT process was induced in recipient non-tumorigenic epithelial MCF-10A cells. Our findings demonstrated that GM1-enriched sEVs derived from breast cancer cells induced the EMT process of recipient cells, which might provide essential information on the biological function of vesicular GM1.

Postoperative survival effect of the number of examined lymph nodes on esophageal squamous cell carcinoma with pathological stage T1-3N0M0.

BACKGROUND: The postoperative survival effect of the number of examined lymph nodes on patients of R0-resected esophageal squamous cell carcinoma with pathological stage T1-3N0M0 is still unclear. METHODS: Patients diagnosed with pathological stage T1-3N0M0 esophageal squamous cell carcinoma from two cancer databases-our cancer center (N = 707), and Surveillance Epidemiology and End Results (N = 151). The primary clinical endpoint was overall survival. The X-tile software was used to determine the optimal cutoff value of the number of examined lymph nodes, and propensity score matching was conducted to reduce selection bias according to the results of X-tile software. The cohort of 151 patients from another database was used for validation. RESULTS: X-tile software provided an optimal cutoff value of 15 examined lymph nodes based on 707 patients, and 231 pairs of matched patients were included. In the unmatched cohort, Cox proportional hazard regression analysis revealed better overall survival in patients with more than 15 examined lymph nodes (adjusted hazard ratio, 0.566, 95% confidence interval, 0.445-0.720; p < 0.001) compared with patients with 15 or fewer examined lymph nodes. In the validation cohort, patients with more than 15 examined lymph nodes also had better overall survival (adjusted hazard ratio 0.665, p = 0.047). CONCLUSIONS: The number of examined lymph nodes is a significant prognostic factor in esophageal squamous cell carcinoma patients with pathological stage T1-3N0M0, and more than 15 examined lymph nodes are associated with better overall survival. Although the difference is not significant, the survival curve of patients with examined lymph nodes > 30 is better than those with examined lymph nodes 15-30. We believe that the number of examined lymph nodes can provide prognostic guidance for those patients, and the more examined lymph nodes cause lesser occult lymph nodes metastasis and lead to a better prognosis. Therefore, surgeons and pathologists should try to examine as many lymph nodes as possible to evaluate the pathological stage precisely. However, we need more validation from other studies.

Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of cyclin-dependent-like kinase 5.

Melatonin helps to maintain circadian rhythm, exerts anticancer activity, and plays key roles in regulation of glucose homeostasis and energy metabolism. Glycosylation, a form of metabolic flux from glucose or other monosaccharides, is a common post-translational modification. Dysregulated glycosylation, particularly O-GlcNAcylation, is often a biomarker of cancer cells. In this study, elevated O-GlcNAc level in bladder cancer was inhibited by melatonin treatment. Melatonin treatment inhibited proliferation and migration and enhanced apoptosis of bladder cancer cells. Proteomic analysis revealed reduction in cyclin-dependent-like kinase 5 (CDK5) expression by melatonin. O-GlcNAc modification determined the conformation of critical T-loop domain on CDK5 and further influenced the CDK5 stability. The mechanism whereby melatonin suppressed O-GlcNAc level was based on decreased glucose uptake and metabolic flux from glucose to UDP-GlcNAc, and consequent reduction in CDK5 expression. Melatonin treatment, inhibition of O-GlcNAcylation by OSMI-1, or mutation of key O-GlcNAc site strongly suppressed in vivo tumor growth. Our findings indicate that melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of CDK5.

A Parsimonious Prognostic Model and Heat Map for Predicting Survival Following Adjuvant Radiotherapy in Parotid Gland Carcinoma With Lymph Node Metastasis.

OBJECTIVES: To construct a simplified prognostic risk model to predict overall survival after adjuvant radiotherapy for parotid gland carcinoma patients with stage T1-4aN1-3M0. MATERIALS AND METHODS: We evaluated 879 patients who were pathological diagnosed as stage T1-4aN1-3M0 parotid gland cancer. Those eligible patients treated with parotidectomy and neck lymph node dissection between 2004 and 2015 in the Surveillance Epidemiology and End Results database. All cases received adjuvant radiotherapy. Independent prognostic factors included in the original model were identified by Cox regression analysis. The primary endpoint was overall survival. The model's prediction power was evaluated by the concordance index. The entire cohort was categorized into new low- and high-risk groups using X-tile software according to the results of prognostic model. Kaplan-Meier method was used to depict the survival curves. And the statistical significance was determined by log-rank test. Besides, a heat map was visually described the association between the survival time and 2 most significant prognostic factors. RESULTS: In the univariable and multivariate analyses, 4 independent factors for overall survival were age, tumor size, pTNM stage, and the number of positive lymph nodes, which were all selected in the parsimonious prognostic model. The concordance indices of the prognostic model and pTNM stage were 0.652 and 0.565, respectively. Patients in the low-risk group had better overall survival over patients in the high-risk group [unadjusted hazard ratio = 2.578, 95% confidence interval 2.095-3.172, P < 0.001]. The results of the heat map revealed that patients with smaller tumor size and fewer positive lymph nodes had much longer survival time. CONCLUSIONS: This parsimonious prognostic model could estimate the long-term survival after adjuvant radiotherapy for parotid gland carcinoma with stage T1-4aN1-3N0M0. The tools may be valuable to guide multidisciplinary team in making treatment decisions.

A prognostic model for stratification of stage IB/IIA esophageal squamous cell carcinoma: a retrospective study.

BACKGROUND: To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). METHODS: Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. RESULTS: Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). CONCLUSION: Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

Fire Performance of Heavyweight Self-Compacting Concrete and Heavyweight High Strength Concrete.

In this study, the fresh and hardened state properties of heavyweight self-compacting concrete (HWSCC) and heavyweight high strength concrete (HWHSC) containing heavyweight magnetite aggregate with 50, 75, and 100% replacement ratio, and their performance at elevated temperatures were explored experimentally. For fresh-state properties, the flowability and passing ability of HWSCCs were assessed by using slump flow, T500 mm, and J-ring tests. Hardened-state properties including hardened density, compressive strength, and modulus of elasticity were evaluated after 28 days of mixing. High-temperature tests were also performed to study the mass loss, spalling of HWSCC and HWHSC, and residual mechanical properties at 100, 300, 600 and 900 °C with a heating rate of 5 °C/min. Ultimately, by using the experimental data, rational numerical models were established to predict the compressive strength and modulus of elasticity of HWSCC at elevated temperatures. The results of the flowability and passing ability revealed that the addition of magnetite aggregate would not deteriorate the workability of HWSCCs and they retained their self-compacting characteristics. Based on the hardened densities, only self-compacting concrete (SCC) with 100% magnetite content, and high strength concrete (HSC) with 75 and 100% magnetite aggregate can be considered as HWC. For both the compressive strength and elastic modulus, decreasing trends were observed by introducing magnetite aggregate to SCC and HSC at an ambient temperature. Mass loss and spalling evaluations showed severe crack propagation for SCC without magnetite aggregate while SCCs containing magnetite aggregate preserved up to 900 °C. Nevertheless, the mass loss of SCCs containing 75 and 100% magnetite content were higher than that of SCC without magnetite. Due to the pressure build-up, HSCs with and without magnetite showed explosive spalling at high temperatures. The residual mechanical properties analysis indicated that the highest retention of the compressive strength and modulus of elasticity after exposure to elevated temperatures belonged to HWSCC with 100% magnetite content.

KIF-2C expression is correlated with poor prognosis of operable esophageal squamous cell carcinoma male patients.

To determine the prognostic significance of Kinesin family member 2C (KIF-2C) expression in patients with operable esophageal squamous cell carcinoma (ESCC), we conducted an immunohistochemical analysis of KIF-2C expression in 415 surgically resected primary tumor tissues and 40 adjacent non-cancerous tissues from patients with operable ESCC. The median duration of postoperative follow-up was 76.0 months. Higher KIF-2C expression was associated with significantly increased risks of higher pathologic tumor (pT) status (P=0.038) and poorer tumor differentiation (P=0.022). For the entire cohort, KIF-2C expression was not an independent factor significantly associated with overall survival (OS) (P=0.097) or disease-free survival (DFS) (P=0.152). In female patients, KIF-2C expression had no effect on OS (P=0.880) and DFS (P=0.864). However, OS (hazard ratio (HR)=1.480, P=0.013) and DFS (HR=1.418, P=0.024) were worse for male patients with high KIF-2C expression compared with male patients with low KIF-2C expression. Moreover, the OS and DFS of male patients with high KIF-2C expression were also significantly shorter compared with female patients with low KIF-2C expression (P=0.022, P=0.029) and female patients with high KIF-2C expression (P=0.014, P=0.018). Based on these findings, KIF-2C expression in tumor tissues promises to serve as an independent prognostic marker for male, but not female, patients with operable ESCC. Prognosis was worse for male patients with high KIF-2C expression compared with patients with the same pathologic tumor-node-metastasis (pTNM) stage.

Inflammation-based prognostic system predicts postoperative survival of esophageal carcinoma patients with normal preoperative serum carcinoembryonic antigen and squamous cell carcinoma antigen levels.

BACKGROUND: The Glasgow Prognostic Score (GPS) is an established inflammation-based system that is used to predict the prognosis for several types of malignancies. In this retrospective study, we assessed the postoperative survival of 725 patients with non-metastatic esophageal squamous cell carcinoma who had normal preoperative serum tumor marker levels according to the GPS. METHODS: Among 1394 patients who underwent esophagectomy between August 2006 and December 2010, 725 with normal preoperative serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were enrolled. All demographic, pathologic, and survival data were analyzed retrospectively. Uni- and multivariate analyses were performed to evaluate the relationship with overall survival. The Kaplan-Meier analysis and log-rank tests were used to compare the survival curves between patients with GPS 0 (group A) and 1 or 2 (group B). RESULTS: Patients in group A exhibited significantly better 3- and 5-year cancer-specific survival (CSS) rates (0.780 and 0.759, respectively) than those in group B (0.624 and 0.605, respectively). Multivariate Cox regression analysis revealed that age, tumor length, pathological tumor-node-metastasis (pTNM) stage, venous invasion, lymph node metastasis, serum albumin and C-reactive protein levels, and GPS were associated with postoperative survival of these patients. Further multivariate analysis confirmed that GPS was an independent prognostic factor. The Kaplan-Meier analysis and log-rank tests demonstrated a significant difference in CSS between groups A and B (P = 0.001). CONCLUSIONS: GPS may be a valuable prognostic indicator for esophageal cancer patients with normal preoperative CEA and SCC-Ag serum levels.

Alcohol and survival in ESCC: prediagnosis alcohol consumption and postoperative survival in lymph node-negative esophageal carcinoma patients.

BACKGROUND: The association between esophageal cancer and prediagnosis alcohol consumption is well established. However, evidence that prediagnosis alcohol consumption affects postoperative survival in patients with lymph node-negative esophageal squamous cell carcinoma (ESCC) is lacking. We conducted a retrospective study on the effect of prediagnosis alcohol consumption on the postoperative survival of patients with lymph node-negative ESCC in China. METHODS: We enrolled 643 ESCC patients with negative lymphatic metastasis who had undergone esophagectomy between 1990 and 2005 at the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China, and reviewed their demographic, pathologic, preoperative, and cancer outcome data obtained from medical records. These data were analyzed using life table and Kaplan-Meier analyses and multivariate Cox regression. RESULTS: There was a significant reduction in 3- and 5-year survival in drinkers with lymph node-negative ESCC. For drinkers, 3- and 5-year survival rates were 43% and 36% respectively, whereas, for nondrinkers, the corresponding values were 63% and 58%, respectively (p < 0.05). Multivariate Cox regression showed that drinking (p = 0.001, relative risk =1.583) was an independent factor for survival in patients with lymph node-negative ESCC. Striated analysis revealed that drinking was an independent factor for survival in patients with stage II A (p = 0.008, relative risk =1.679), stage IB (p = 0.044, relative risk=1.517), and well (p=0.011, relative risk =1.783) and moderately (p = 0.002, relative risk = 1.915) differentiated ESCC. CONCLUSIONS: Prediagnosis alcohol consumption is an independent prognostic factor for postoperative survival in patients with lymph node-negative ESCC.

Right versus left transthoracic approach for lymph node-negative esophageal squamous cell carcinoma.

BACKGROUND: To compare the right and left transthoracic approach on the post-operative survival of patients with lymph node-negative esophageal squamous cell carcinoma. METHODS: Six hundred and ninety-five ESCC patients who underwent esophagectomy between 1990 and 2005 were retrospectively enrolled in the present study and were confirmed by histology to be of no lymph node metastasis. Those who had received neoadjuvant chemotherapy or radiotherapy were excluded from the study. Patients were divided into two groups, the left (n=545) and right (n=150) transthoracic groups. The follow-up duration ranged from 1 to 20 years with a mean of 7 years. Kaplan-Meier and univariate and multivariate Cox proportional hazards were used for analysis. RESULTS: 3- and 5-year CSS rates were 62.0 % and 44.0 % in the left group, while the corresponding figures in the right group were 56.0 % and 40.0 %(P<0.05). The overall survival for the two groups was significantly different (P=0.045). Survival analyses were stratified by stages, which found that the favorable survival advantage was not present. When the survival curves were stratified by tumor locations, a significant difference was not revealed. Surgical approaches were regarded as one of the prognostic factors in the univariate analysis (P=0.019). However, this significance could not be confirmed in multivariate Cox regression analysis (P=0.193). CONCLUSIONS: The left transthoracic approach is superior in some aspects to the right transthoracic approach regarding surgical and oncological outcomes in the treatment of lymph node negative ESCC.

Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma.

AIM: To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio (NLR) in esophageal squamous cell carcinoma (ESCC). METHODS: Data from 371 eligible patients with ESCC who had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ(2) test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival (CSS) and recurrence-free survival (RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied. RESULTS: The median age of the patients was 57.0 years, and 276/371 (74.4%) patients were male. The NLR was ≤ 3.0 in 80.1% (297/371) of the patients, and the remaining 19.9% (74/371) had an NLR > 3.0. Median postoperative follow-up was 66.0 mo [interquartile range (IQR): 49.0-76.0 mo], with a follow-up rate of 94%. Follow-up was not significantly different between patients with an NLR ≤ and > 3.0 (63.13 ± 1.64 vs 61.52 ± 3.66, P = 0.711). However, higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status (P = 0.007). A significant, independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS (HR = 1.591; P = 0.007) and RFS (HR = 1.525; P = 0.013). Moreover, when patients were stratified by pathological tumor-node-metastasis (TNM) staging, the adverse effects of preoperative serum NLR on CSS (HR = 2.294; P = 0.008) and RFS (HR = 2.273; P = 0.008) were greatest in those patients with stage IIIA disease. CONCLUSION: Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients, particularly in patients with stage IIIA disease.

Three-field vs two-field lymph node dissection for esophageal cancer: a meta-analysis.

AIM: To assess the effects of 3-field lymphadenectomy for esophageal carcinoma. METHODS: We conducted a computerized literature search of the PubMed, Cochrane Controlled Trials Register, and EMBASE databases from their inception to present. Randomized controlled trials (RCTs) or observational epidemiological studies (cohort studies) that compared the survival rates and/or postoperative complications between 2-field lymphadenectomy (2FL) and 3-field lymphadenectomy (3FL) for esophageal carcinoma with R0 resection were included. Meta-analysis was conducted using published data on 3FL vs 2FL in esophageal carcinoma patients. End points were 1-, 3-, and 5-year overall survival rates and postoperative complications, including recurrent nerve palsy, anastomosis leak, pulmonary complications, and chylothorax. Subgroup analysis was performed on the involvement of recurrent laryngeal lymph nodes. RESULTS: Two RCTs and 18 observational studies with over 7000 patients were included. There was a clear benefit for 3FL in the 1- (RR = 1.16; 95%CI: 1.09-1.24; P < 0.01), 3- (RR = 1.44; 95%CI: 1.19-1.75; P < 0.01), and 5-year overall survival rates (RR = 1.37; 95%CI: 1.18-1.59; P < 0.01). For postoperative complications, 3FL was associated with significantly more recurrent nerve palsy (RR = 1.43; 95%CI: 1.28-1.60; P = 0.02) and anastomosis leak (RR = 1.26; 95%CI: 1.05-1.52; P = 0.09). In contrast, there was no significant difference for pulmonary complications (RR = 0.93; 95%CI: 0.75-1.16, random-effects model; P = 0.27) or chylothorax (RR = 0.77; 95%CI: 0.32-1.85; P = 0.69). CONCLUSION: This meta-analysis shows that 3FL improves overall survival rate but has more complications. Because of the high heterogeneity among outcomes, definite conclusions are difficult to draw.