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1.
J Hazard Mater ; 408: 124931, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33373954

RESUMO

Lead pollution precaution caused by lead-based anode corrosion is a hot and challenging issue for zinc electrowinning. A novel functional lead-based anode (MnO2 pre-coated anode-MPA) was precisely fabricated and its long-term performances were studied compared with typical Pb-1%Ag anode (TPA). Results indicated that MPA posed excellent effects on synergistic inhibiting lead dissolution and reducing hazardous pollutants generation, and decreasing the lead content of zinc products by 81%. Further, the underlying mechanism of film growth and transformation in structure, composition and crystal phase, the migration and distribution of lead and anode slime during electrolytic, were clarified in-depth. Dynamic material flow analysis confirmed that MPA reduced the entire lead migration amount by over 92% compared with TPA. The compact multilayer structure of the MPA film and self-reparation effects of local structure provided better and persistent protection for the lead matrix, which greatly retarded the high-speed corrosion of lead anode. Compared with α-MnO2 in TPA, the formation and maintenance of γ-MnO2 in MPA accelerated the oxygen evolution reaction and inhibited the anode slime generation. This finding provides new insights in pollution precaution and control by designing and tuning new functional anode in hydrometallurgy process.

2.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33223508

RESUMO

The histone H3 lysine 36 methyltransferase SET-domain-containing 2 (SETD2) has been reported to be frequently mutated or deleted in many types of human cancer. However, the role of SETD2 in lung adenocarcinoma (LUAD) has not been well documented. In the present study, we found that SETD2 was significantly down-regulated both in LUAD tissues and cell lines. Functionally, the increased expression of SETD2 significantly attenuated the proliferation of cancer cells by affecting the cell cycle, whereas SETD2 deficiency dramatically improved these proliferative abilities of cancer cells. Through conjoint analysis of RNA-seq and ChIP data, we identified a functional target gene of SETD2, CXCL1, and its expression was negatively correlated with that of SETD2. Moreover, SETD2 deletion stimulated cell cycle-related proteins to promote LUAD. Further mechanistic studies demonstrated that histone H3 lysine 36 trimethylation (H3K36me3) catalyzed by SETD2 interacted with the promoter of CXCL1 to regulate its transcription and downstream signaling pathways, contributing to tumorigenesis in vitro and in vivo. Our findings suggested that SETD2 inhibited tumor growth via suppressing CXCL1-mediated activation of cell cycle, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream CXCL1 might represent a potential therapeutic way for new treatment in LUAD.

3.
Sci Total Environ ; : 142502, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33066963

RESUMO

The tradeoff between economic growth and environmental protection has been a critical issue in facilitating eco-industrial park development in China. As the principal contributors to China's industrial output, many industrial parks have been addressing the issues of intensive resource consumption and pollutant generation, driven by much stricter regulations on the environment and resource management. Retuning the industrial structure is a substantial way to address the environmental issues while promoting economic development, which are the goals of eco-industrial development. This study proposes a multi-criteria industrial structure adjustment model by employing a generalized reduced gradient method to find the optimal structure of an industrial park. The model aims to increase the overall resource utilization efficiency and industrial output efficiency through a decoupling between the economic development and environmental burden of the park. A Chinese eco-industrial park located in the capital, the Beijing Economic-technological Development Area (BDA), is used as an example to uncover a transformation roadmap from a high-speed mode to a high-quality mode. The constraints of the multi-criteria decision-making model mainly focus on the limits of water consumption and pollutant emissions by targeting an appropriate economic development rate. The key findings are as follows. First, BDA could achieve 186% economic growth with 20% water consumption and 30% contaminant reduction in five years (2020-2025) by optimizing the industrial structure. Second, the advanced manufacturing industries play significant roles in stimulating the high-quality development. Third, ammonia nitrogen is a crucial factor restricting economic development under the requests of the "dual control" policy. Forth, the industry that can use reclaimed water in production will get more development opportunities and space, and vice versa. The model can be applied in diverse industrial parks by modifying the parameters and associated constraints.

4.
Cancer Immunol Res ; 8(11): 1381-1392, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32917659

RESUMO

Immune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment by prolonging overall survival of patients with cancer. Despite advances in the clinical setting, the immune cellular network in the tumor microenvironment (TME) that mediates such therapy is not well understood. IL33 is highly expressed in normal epithelial cells but downregulated in tumor cells in advanced carcinoma. Here, we showed that IL33 was induced in tumor cells after treatment with ICB such as CTL antigen-4 (CTLA-4) and programmed death-1 (PD-1) mAbs. ST2 signaling in nontumor cells, particularly CD8+ T cells, was critical for the antitumor efficacy of ICB immunotherapy. We demonstrated that tumor-derived IL33 was crucial for the antitumor efficacy of checkpoint inhibitors. Mechanistically, IL33 increased the accumulation and effector function of tumor-resident CD103+CD8+ T cells, and CD103 expression on CD8+ T cells was required for the antitumor efficacy of IL33. In addition, IL33 also increased the numbers of CD103+ dendritic cells (DC) in the TME and CD103+ DC were required for the antitumor effect of IL33 and accumulation of tumor-infiltrating CD8+ T cells. Combination of IL33 with CTLA-4 and PD-1 ICB further prolonged survival of tumor-bearing mice. Our study established that the "danger signal" IL33 was crucial for mediating ICB cancer therapy by promoting tumor-resident adaptive immune responses.

5.
Oncol Lett ; 20(3): 2655-2664, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782582

RESUMO

The presence of tumor infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissues are of great prognostic significance in several types of human cancer. The present study investigated the density of TILs and TLSs in gastric cancer (GC) tissues and their association with pathological parameters. Moreover, the clinical significance of follicular CD8+ cytotoxic T cells present within the germinal centers of the tumor-associated TLSs was investigated. Immunohistochemistry and H&E staining were used to examine the infiltration and distribution patterns of TILs, TLSs and germinal center (gc) CD8+ TILs in tumor tissues obtained from 63 patients with GC. The number of TILs, TLSs, combination of TILs and TLSs (TILs-TLSs) and gcCD8+ TILs were used to define tumoral immune parameters, and the prognostic value of these parameters was assessed. The analysis revealed that patients with GC with increased levels of TILs, TLSs, or gcCD8+ TILs exhibited improved overall survival. In addition, gcCD8+ TILs levels were significantly associated with patient age, histological grade and pTN stage. Increased levels of TILs-TLSs were positively associated with nerve invasion, tumor thrombus, nodal metastasis and histological grade. Multivariate Cox regression analysis revealed that TILs-TLSs and gcCD8+ TILs were independent prognostic factors. The data obtained in the present study demonstrated that high levels of tumoral immune parameters are important independent prognostic predictors for human GC. The results also suggested a possible role of gcCD8+ TILs in tumor immune surveillance.

6.
Water Res ; 185: 116213, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32731077

RESUMO

Reliable and accurate oxygen-input control, which is critical to maintaining efficient nitrogen removal performance for partial nitritation-anammox (PN-A) process, remains one of the main operational difficulties. In this study, a novel, yet simple system (a simple process for autotrophic nitrogen-removal, SPAN) with precise oxygen-input control was developed to treat ammonium-rich wastewater via PN-A process. SPAN brings oxygen to biomass by circulating water and creating water spray (shower) at the water-air interface, and effectively balances the activities of core functional microorganisms through precise oxygen-input control. The oxygen-input rate is decided by the water circulation rate and shower rate and is measurable and predictable. Therefore, the required amount of oxygen for ammonium oxidation can be precisely delivered to the biomass by adjusting the circulation rate and shower rate. The results of two parallel SPAN reactors demonstrated that during long-term operation, the required oxygen input was precisely and reliably controlled. More than 99% of NH4+-N and 81% - 85% of total nitrogen were stably removed, with anammox bacteria contributing to more than 96% of total nitrogen removal. Anammox bacteria were efficiently enriched to the highest level among the key nitrogen-converting microbial groups, both in terms of abundance (8.17%) and nitrogen-conversion capacity, while ammonium oxidizing bacteria were well controlled to provide sufficient ammonium-oxidizing capacity. Nitrite oxidizing bacteria were maintained stable (relative abundance of 1.08%-1.88%) and their activity was effectively suppressed. This study provided a novel technology, SPAN, to precisely control oxygen input in PN-A system, and proved that SPAN was effective and reliable in achieving long-term high-efficiency nitrogen removal.


Assuntos
Compostos de Amônio , Eliminação de Resíduos Líquidos , Reatores Biológicos , Nitrogênio , Oxirredução , Oxigênio , Águas Residuárias
7.
Huan Jing Ke Xue ; 41(3): 1116-1122, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608612

RESUMO

Volatile organic compounds (VOCs) are one of the key atmospheric pollutants associated with great impact on air quality. Industrial sources have become the most important source of VOCs emissions in China, of which the chemical industry accounts for a large part. At present, more than half of chemical manufacturers are clustered in chemical industrial parks (CIPs), thus the control of VOCs in CIPs is crucial. This study analyzed the production processes of the fine chemical industry and the principle of VOCs production, and then proposed an accounting model of VOCs emissions associated with production processes, based on a typical fine chemical industrial park:Hangzhou Bay Shangyu Economic and Technological Development Area (HSEDA). The quantity of VOCs generation in the main production processes, such as feeding, heating, chemical reaction gas take-off, cleaning, vacuum pumping, pressure release, and evaporating, were calculated. Meanwhile, the chemical process simulation software Aspen was also employed to simulate the VOCs generation in these processes. The methods were applied to 14 representative products in HSEDA and the feature of VOCs generation in the chemical processes mentioned above, and components were revealed. The results of the two methods were compared, and the difference between the two methods was within±22% except for the pressure release process. The model and accounting methods proposed in this study will have sound applicability in accounting for VOCs emissions in fine chemical industrial parks underpinned by quantitative chemical industry production parameters.

8.
Int J Med Inform ; 141: 104195, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32485554

RESUMO

OBJECTIVE: Ovarian cancer (OC) is one of the most common types of cancer in women. Accurately prediction of benign ovarian tumors (BOT) and OC has important practical value. METHODS: Our dataset consists of 349 Chinese patients with 49 variables including demographics, blood routine test, general chemistry, and tumor markers. Machine learning Minimum Redundancy - Maximum Relevance (MRMR) feature selection method was applied on the 235 patients' data (89 BOT and 146 OC) to select the most relevant features, with which a simple decision tree model was constructed. The model was tested on the rest of 114 patients (89 BOT and 25 OC). The results were compared with the predictions produced by using the risk of ovarian malignancy algorithm (ROMA) and logistic regression model. RESULTS: Eight notable features were selected by MRMR, among which two were identified as the top features by the decision tree model: human epididymis protein 4 (HE4) and carcinoembryonic antigen (CEA). Particularly, CEA is a valuable marker for OC prediction in patients with low HE4. The model also yields better prediction result than ROMA. CONCLUSION: Machine learning approaches were able to accurately classify BOT and OC. Our goal is to derive a simple predictive model which also carries a good performance. Using our approach, we obtained a model that consists of just two biomarkers, HE4 and CEA. The model is simple to interpret and outperforms the existing OC prediction methods. It demonstrates that the machine learning approach has good potential in predictive modeling for the complex diseases.

9.
Microb Ecol ; 79(2): 342-356, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31428833

RESUMO

Current technologies could identify the abundance and functions of specific microbes, and evaluate their individual effects on microbial ecology. However, these microbes interact with each other, as well as environmental factors, in the form of complex network. Determination of their combined ecological influences remains a challenge. In this study, we developed a tripartite microbial-environment network (TMEN) analysis method that integrates microbial abundance, metabolic function, and environmental data as a tripartite network to investigate the combined ecological effects of microbes. Applying TMEN to analyzing the microbial-environment community structure in the sediments of Hangzhou Bay, one of the most seriously polluted coastal areas in China, we found that microbes were well-organized into 4 bacterial communities and 9 archaeal communities. The total organic carbon, sulfate, chemical oxygen demand, salinity, and nitrogen-related indexes were detected as crucial environmental factors in the microbial-environmental network. With close interactions with these environmental factors, Nitrospirales and Methanimicrococcu were identified as hub microbes with connection advantage. Our TMEN method could close the gap between lack of efficient statistical and computational approaches and the booming of large-scale microbial genomic and environmental data. Based on TMEN, we discovered a potential microbial ecological mechanism that crucial species with significant influence on the microbial community ecology would possess one or two of the community advantages for enhancing their ecological status and essentiality, including abundance advantage and connection advantage.


Assuntos
Archaea/fisiologia , Fenômenos Fisiológicos Bacterianos , Baías/microbiologia , Sedimentos Geológicos/microbiologia , Consórcios Microbianos , Técnicas Microbiológicas/métodos , China
10.
Huan Jing Ke Xue ; 40(11): 5024-5031, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854570

RESUMO

Wastewater treatment plants (WWTPs) are regarded as the main source for antibiotic resistant genes (ARGs). To explore the features regarding the distribution of ARGs in wastewater with complicated composition in treatment plants, wastewater samples from a chemical industry park that produced antibiotics were selected. qPCR was applied to detect the type and abundance of ARGs in the wastewater flows from the WWTPs. The results indicated that 16 types of ARGs were detected from the wastewater from the WWTPs, among which sulfonamide resistance genes and tetracycline resistance genes were the dominant ARGs that appeared in the wastewater. Additionally, intI 1 was detected and its abundance was correlated with that of sulfonamide resistance genes. This indicated that intI 1 may promote the migration and transformation of sulfonamide resistance genes. The pharmaceutical factories in the park mainly synthesize macrolide antibiotics. Because of the selective pressure, the absolute abundance of ermB in the wastewater was much higher than that in the other industrial wastewater. The total ARGs decreased by 1.16 log via traditional biological treatment process, and the total ARGs decreased by 2.46 log via the Fenton process. The results showed that the removal effects of deep treatment processes on ARGs were better than that of biological treatment in this wastewater treatment process. Highly abundant and movable ARGs already exist in the water body, and their release from WWTPs without effective treatment poses high risks to the environment.


Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Águas Residuárias , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Eliminação de Resíduos Líquidos
11.
Onco Targets Ther ; 12: 8139-8149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632065

RESUMO

Background: IFIT2 (interferon-induced proteins with tetratricopeptide repeats 2), also known as ISG54, is an important interferon-stimulated gene family protein, which has been confirmed to play a crucial role in anti-cancer as well as anti-virus process. In the present study, we aimed to investigate the IFIT2 expression in human non-small-cell cancer (NSCLC) tissues and its clinical implications. Methods: The immunohistochemistry assay was used to identify the clinical significance and prognostic value of IFIT2 expression in NSCLC tissues. The depletion of IFIT2 was achieved using RNAi approach to assess the role of IFIT2 in the regulation of biological behaviors in human lung cancer cell lines. Results: Decreased IFIT2 expression was found in human NSCLC tissues (both in lung adenocarcinoma and lung squamous cell carcinoma) in contrast to the adjacent normal tissues (both P<0.0001, respectively). We did not find any significant correlations between the IFIT2 expression and patient's clinicopathological features. The survival analysis showed that the overall survival (OS) of patients in IFIT2 low expression group was significantly poorer than that in IFIT2 high expression group (in lung adenocarcinoma: P=0.027; and in lung squamous cell carcinoma: P=0.029). The Cox model analysis also indicated that the distant metastasis (P=0.043) could be used as an independent prognostic factor for lung adenocarcinoma patients, and the lymph node metastasis (P=0.045) and IFIT2 low expression (P=0.020) could be used as independent prognostic factors for lung squamous cell carcinoma patients. Moreover, the depletion of IFIT2 in human lung cancer cell lines A549, H1975 and SK-MES-1 significantly increased the cellular abilities, such as viability, migration and invasion. Conclusion: Decreased IFIT2 was involved in the initiation and the progression of human NSCLC, and its underlying mechanisms still needs further investigation.

12.
Acta Histochem ; 121(5): 657-663, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153587

RESUMO

The prognostic significance and clinical implications of resident CD103+CD8+T cells in human colorectal cancer tissues still remains largely unexplored. In our present study, we aimed to characterize the resident CD8+T cells in human colorectal cancer tissues by using double staining of CD103 and CD8, and further evaluated the prognostic significance of resident CD8+T cells in colorectal cancer. We found that the OS rate of the colorectal cancer patients with higher infiltration of CD8+T cells, or with higher numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues was significantly better than that of the patients with lower infiltration of CD8+T cells, or with lower numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues, respectively. Moreover, higher infiltration of CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with advanced TNM stage. Higher numbers of resident CD103+CD8+T cells in colorectal cancer tissues were significantly and inversely correlated with distant metastasis status. Higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with age status. The COX model analysis demonstrated that higher infiltration of CD8+T cells, higher numbers of resident CD103+CD8+T cells, or higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues, could serve as independent prognostic predictors for colorectal cancer patients. Taken together, our present study demonstrated the density of tumor infiltrating CD8+T cells or the numbers of resident CD103+CD8+T cells in colorectal tissues could be used as an important prognostic predictor for this malignancy.


Assuntos
Antígenos CD/análise , Linfócitos T CD8-Positivos , Neoplasias Colorretais/mortalidade , Cadeias alfa de Integrinas/análise , Linfócitos do Interstício Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos CD8/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Cadeias alfa de Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Subpopulações de Linfócitos T
13.
J Transl Med ; 17(1): 178, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138322

RESUMO

BACKGROUND: T-cell immunoglobulin and mucin domain 1 (TIM-1) is an important co-stimulatory molecule which serves as a surface marker for T cell activation, especially for Th2 cells. Recently, many studies have also shown that TIM-1 can be abnormally expressed in human cancers and may have a potential role in promoting cancer progression. METHODS: The immunohistochemistry was used to examine the TIM-1 expression in human non-small-cell lung carcinoma (NSCLC) tissues. The cellular studies were performed to investigate the role of TIM-1 in the regulation of biological functions of human lung cancer cell lines. RESULTS: We found that the TIM-1 expression was increased in human NSCLC tissues compared with the adjacent normal tissues, and the OS rate of NSCLC patients with higher TIM-1 expression was significantly lower compared with the ones with lower TIM-1 expression. The COX model showed that higher TIM-1 expression in lung cancer tissues could be used as an independent prognostic predictor for the patients. Furthermore, we depleted TIM-1 in NSCLC cell lines A549 and SK-MES-1, and the cellular functional studies also revealed that depletion of TIM-1 could significantly inhibit the cell viability as well as the abilities of migration and invasion. In addition, our microarray data showed that certain signaling pathways were altered and enriched after depletion of TIM-1. We subsequently verified that PI3K/Akt signaling pathway was involved in the TIM-1-mediated regulation of cellular functions in NSCLC cells. CONCLUSION: Our findings supported the notion that TIM-1 could serve as a potential therapeutic target for NSCLC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Neoplasias Pulmonares/diagnóstico , Células A549 , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise Serial de Tecidos , Células Tumorais Cultivadas
14.
Cancer Cell Int ; 19: 106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043861

RESUMO

Background: Nectin-4, also known as PVRL4 (poliovirus-receptor-like 4), is specifically expressed in the embryo and placenta. Recent studies have reported that the Nectin-4 is over-expressed in multiple human cancers, and such abnormal expression is associated with cancer progression and poor prognosis of the patients. In the present study, we aimed to characterize the expression pattern of Nectin-4 in human esophageal cancer (EC) tissues, and to investigate its clinical implications, prognostic value and regulatory effects on cellular functions of EC cells. Methods: In the present study, we first examined Nectin-4 expression in human EC tissues by using immunohistochemistry (IHC) assay and analyzed the clinical associations. Then the cellular studies in vitro and the nude mice tumor model in vivo were used to examine the regulatory role of Nectin-4 in the progression of EC. Results: Our results demonstrated that over-expression of Nectin-4 in human EC tissues was significantly associated with tumor size, depth of tumor invasion, and poor prognosis of the patients. The intervention of Nectin-4 expression in EC cell lines showed that the increased Nectin-4 expression could significantly promote the cell viability, migration, invasion and tumor formation. Conclusions: Our present data unveiled that Nectin-4 played an important role in tumor biology and could serve as a useful prognostic predictor of human EC.

15.
Cancer Cell Int ; 19: 101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31015801

RESUMO

Background: It is well known that human clear cell renal cell carcinoma (ccRCC) is a highly immunogenic and chemo-resistant tumor. Recently, emerging data suggest that the immune checkpoint blockade therapy is an important breakthrough in the treatment against ccRCC. HHLA2, a recently reported member of B7 family, is uniquely expressed in humans but not in mice, and it plays an important role in the functional inhibition of CD4 and CD8 T cells. Herein, we aimed to study the clinical implications of HHLA2 expression in human ccRCC and its potential regulatory role in the biological functions of the cancer cells. Methods: In the present study, we examined HHLA2 expression in human ccRCC tissues and analyzed the clinical implications as well as prognostic value. The intervention of HHLA2 in human ccRCC cell lines ACHN and 786-O was performed and its effect on the cellular function of the cells was also analyzed. We also identified the differentially expressed genes upon HHLA2 knockdown in ccRCC cell lines by using gene microarray analysis. Results: We found that higher HHLA2 mRNA expression level in human ccRCC tissues compared with that in adjacent normal tissues based on TCGA data, and the HHLA2 expression at mRNA level was positively and significantly correlated with PD-L1, PD-L2, B7-H6, but negatively and significantly correlated with B7-H3. Moreover, our immunohistochemistry study showed that the staining intensity of HHLA2 in human ccRCC tissues was significantly higher than that in the adjacent normal tissues, and the overall survival rate of ccRCC patients with higher HHLA2 expression was significantly poorer than that of the patients with lower HHLA2 expression. Higher expression of HHLA2 in ccRCC tissues was positively and significantly associated with larger tumor size and advanced TNM stage. The COX model revealed that the parameters including patient's age, TNM stage and HHLA2 expression level could be used as the independent risk factors respectively for the prognostic prediction of the patients. Our cellular study showed that upon knockdown of HHLA2 expression in human ccRCC cell lines, the cell viability, the migration and the invasion ability were significantly inhibited, while the cell cycle arrest at G1 phase was induced and the expressions of Cyclin D1, c-Myc and Cyclin E1 were decreased. In addition, according to the microarray data, the expressions of epithelia-to-mesenchymal transition markers, such as E-cadherin, N-cadherin and Vimentin, were significantly changed after knockdown of HHLA2 expression. Conclusions: Our findings indicated that HHLA2 was involved in the progression of human ccRCC and could be used as an important prognostic predictor for this malignancy.

16.
Mol Cancer ; 18(1): 47, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925892

RESUMO

BACKGROUND: It has been well established that circular RNAs (circRNAs) play an important regulatory role during tumor progression. Recent studies have indicated that even though circRNAs generally regulate gene expression through miRNA sponges, they may encode small peptides in tumor pathogenesis. However, it remains largely unexplored whether circRNAs are involved in the tumorigenesis of colon cancer (CC). METHODS: The expression profiles of circRNAs in CC tissues were assessed by circRNA microarray. Quantitative real-time PCR, RNase R digestion assay and tissue microarray were used to confirm the existence and expression pattern of circPPP1R12A. The subcellular distribution of circPPP1R12A was analyzed by nuclear mass separation assay and fluorescence in situ hybridization (FISH). SDS-PAGE and LC/MS were employed to evaluate the protein-coding ability of circPPP1R12A. CC cells were stably transfected with lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPPP1R12A and its encoded protein circPPP1R12A-73aa. RNA-sequencing and Western blotting analysis were furthered employed to identify the critical signaling pathway regulated by circPPP1R12A-73aa. RESULTS: We firstly screened the expression profiles of human circRNAs in CC tissues and found that the expression of hsa_circ_0000423 (termed as circPPP1R12A) was significantly increased in CC tissues. We also found that circPPP1R12A was mostly localized in the cytoplasm of CC cells. Kaplan-Meier analysis showed that patients with higher levels of circPPP1R12A had a significantly shorter overall survival. By gain- and loss-of-function approaches, the results suggested that circPPP1R12A played a critical role in proliferation, migration and invasion of CC cells. Furthermore, we showed that circPPP1R12A carried an open reading frame (ORF), which encoded a functional protein (termed as circPPP1R12A-73aa). Next, we found that PPP1R12A-C, not circPPP1R12A, promoted the proliferation, migration and invasion abilities of CC in vitro and in vivo. Finally, we identified that circPPP1R12A-73aa promoted the growth and metastasis of CC via activating Hippo-YAP signaling pathway. In addition, the YAP specific inhibitor Peptide 17 dramatically alleviated the promotive effect of circPPP1R12A-73aa on CC cells. CONCLUSIONS: In the present study, we illustrated the coding-potential of circRNA circPPP1R12A in the progression of CC. Moreover, we identified that circPPP1R12A-73aa promoted the tumor pathogenesis and metastasis of CC via activating Hippo-YAP signaling pathway. Our findings might provide valuable insights into the development of novel potential therapeutic targets for CC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/secundário , Fosfatase de Miosina-de-Cadeia-Leve/genética , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Ciclo Celular , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Fosfoproteínas/genética , Prognóstico , Proteínas Serina-Treonina Quinases/genética , RNA Circular , Taxa de Sobrevida , Fatores de Transcrição , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Front Immunol ; 10: 71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30761139

RESUMO

The tumor microenvironment (TME) is the internal environment of malignant tumor progression, and the host antitumor immune response and normal tissue destruction occur in the TME. Tumor-infiltrating lymphocytes (TIL) is a crucial component of the TME and reflect the host antitumor immune response. The purpose of this study was to discuss the methodology for TIL evaluation and assess the prognostic value of TIL in gastric cancer. In total, we reviewed 1,033 gastrectomy cases between 2002 and 2008 at the Third Affiliated Hospital of Soochow University. To understand the prognostic value of TIL in gastric cancer (GC), TIL were assessed by optical microscopy, and verified by immunohistochemistry. There is no current consensus on TIL scoring in GC. In this study, we discussed a TIL evaluation system that includes an analysis of the amount and percentage of TIL in a tumor. Ultimately, 439 (52.7%) cases showed high levels of TIL and 394 (47.3%) cases had low levels. There was a statistically significant relationship among TIL, tumor size, histological grade, LN metastasis, nerve invasion, tumor thrombus, pTN stage, and WHO subtypes (p < 0.001, respectively). TILhi was a positive significant predictor of overall survival (OS) in Kaplan-Meier survival analysis (P < 0.001) and multivariate Cox regression analysis (HR = 0.431, 95% CI: 0.347-0.534, P < 0.001). After surgery, patients with malignant tumors underwent chemoradiotherapy according to standard therapeutic guidelines based on TNM stage. The TNM scoring system cannot reflect the full information of TME; therefore, TIL can be used as a diagnostic supplement. We constructed a nomogram model that showed more predictive accuracy for OS than pTN stage. In summary, this study proves that high levels of TIL are associated with a positive prognosis and that TIL reflect the protective host antitumor immune response.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Complexo CD3/imunologia , Quimiorradioterapia , Confiabilidade dos Dados , Feminino , Gastrectomia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Microscopia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Carga Tumoral , Microambiente Tumoral/imunologia
18.
Huan Jing Ke Xue ; 40(2): 768-773, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628342

RESUMO

The influence of temperature (30-45℃) and ammonia-nitrogen volume load on the nitrification function and microbial community of activated sludge in an aerobic tank of a sewage treatment plant were investigated under simulated high-temperature stress in the summer. Meanwhile, the bioaugmentation effectiveness of the middle-temperature-enriched nitrifying sludge (with or without acclimation) was evaluated in two biological treatment systems under high-temperature shock. The results showed that the ammonium-nitrogen (NH4+-N) removal efficiency and the nitrifying bacteria content of the aerobic activated sludge at 30-40℃ were above 90% and up to 4.55% and decreased to 40% and 1.97% at 45℃, respectively. To quickly recover the nitrification function of the biological system under high-temperature shock in the summer, the middle-temperature-enriched nitrifying sludge was acclimated at 40℃ for 61 d and achieved (60±5) mg·(L·h)-1 nitrification activity. Then, its bioaugmentation efficiency was compared with that of the middle-temperature-enriched nitrifying sludge. In the bioaugmentation test, 10% of NH4+-N was removed in the reactor inoculated with 5% (volume fraction) of the acclimated nitrifying sludge, while the reactor needed inoculate with 10% (volume fraction) of the middle-temperature-enriched sludge to achieve the same removal efficiency. The results suggested that middle-temperature-enriched nitrifying sludge, after acclimating at 40℃, has a better enhancement effect under a high-temperature shocking load.


Assuntos
Reatores Biológicos , Nitrificação , Esgotos , Eliminação de Resíduos Líquidos/métodos , Temperatura Alta , Estações do Ano
19.
Sci Total Environ ; 647: 1188-1198, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30180327

RESUMO

This study investigated the performance and microbial community dynamics of a start-up method for the partial nitritation-anammox (PN-A) process: start-up from return sludge in an intermittently aerated sequencing batch reactor (IASBR). The robustness of this PN-A IASBR system in achieving long-term efficient nitrogen removal was also investigated. Stable partial nitritation with nitrite accumulation ratio of about 80% was firstly achieved in the IASBR. Then, PN-A process with total nitrogen removal of up to 81.5% was established due to the thriving of anammox bacteria Candidatus Kuenenia resulting from the reduction of the aeration rate. Molecular analysis showed that both bacterial and archaeal communities shifted greatly throughout the start-up stage and the PN-A stage. Besides bacterial genus Nitrosomonas, ammonium-oxidizing archaea (AOA) Candidatus Nitrososphaera with a high abundance of 3.44% also contributed to partial nitritation. Nitrospira was effectively restrained (abundance <1.6%) while methanogens co-existed with the aerobic and anaerobic nitrogen-conversion microorganisms. This study showed that IASBR configuration was efficient in starting up the PN-A process from return sludge, maintaining long-term efficient nitrogen removal and triggering the thrive of AOA.


Assuntos
Reatores Biológicos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Compostos de Amônio/metabolismo , Nitritos/metabolismo , Nitrogênio/metabolismo , Oxirredução , Esgotos
20.
Biochem Biophys Res Commun ; 508(2): 527-535, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30509491

RESUMO

Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of Non-small cell lung cancer (NSCLC), however, the molecular mechanisms of circRNAs in cell proliferation, invasion and TKI drug resistance remain largely undetermined. Here, we identified hsa_circ_0004015 was upregulated in NSCLC tissues, and was associated with the poor overall survival rate of NSCLC patients. Knockdown of hsa_circ_0004015 significantly decreased cell viability, proliferation, and invasion, whereas overexpression exhibited opposed effects in vivo and in vitro. Furthermore, hsa_circ_0004015 could enhance the resistance of HCC827 to gefitinib. In mechanism, hsa_circ_0004015 acted as a sponge for miR-1183, and PDPK1 was revealed to be target gene of miR-1183. Subsequently, functional assays illustrated that the oncogenic effects of hsa_circ_0004015 was attributed to the regulation of miR-1183/PDPK1 axis. In conclusion, circ_0016760/miR-1183/PDPK1 signaling pathway might play vital roles in the tumorigenesis of NSCLC.


Assuntos
Carcinogênese/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistência a Medicamentos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , RNA/farmacologia , Transdução de Sinais , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Carcinogênese/patologia , Proliferação de Células/genética , Células Cultivadas , Gefitinibe/farmacologia , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Circular
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