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1.
J Nanobiotechnology ; 19(1): 58, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632231

RESUMO

The combination of an immuno-metabolic adjuvant and immune checkpoint inhibitors holds great promise for effective suppression of tumor growth and invasion. In this study, a pH-responsive co-delivery platform was developed for metformin (Met), a known immuno-metabolic modulator, and short interfering RNA (siRNA) targeting fibrinogen-like protein 1 mRNA (siFGL1), using a hybrid biomimetic membrane (from macrophages and cancer cells)-camouflaged poly (lactic-co-glycolic acid) nanoparticles. To improve the endo-lysosomal escape of siRNA for effective cytosolic siRNA delivery, a pH-triggered CO2 gas-generating nanoplatform was developed using the guanidine group of Met. It can react reversibly with CO2 to form Met-CO2 for the pH-dependent capture/release of CO2. The introduction of Met, a conventional anti-diabetic drug, promotes programmed death-ligand 1 (PD-L1) degradation by activating adenosine monophosphate-activated protein kinase, subsequently blocking the inhibitory signals of PD-L1. As a result, siFGL1 delivery by the camouflaged nanoparticles of the hybrid biomimetic membrane can effectively silence the FGL1 gene, promoting T-cell-mediated immune responses and enhancing antitumor immunity. We found that a combination of PD-L1/programmed death 1 signaling blockade and FGL1 gene silencing exhibited high synergistic therapeutic efficacy against breast cancer in vitro and in vivo. Additionally, Met alleviated tumor hypoxia by reducing oxygen consumption and inducing M1-type differentiation of tumor-related macrophages, which improved the tumor immunosuppressive microenvironment. Our results indicate the potential of hybrid biomimetic membrane-camouflaged nanoparticles and combined Met-FGL1 blockade in breast cancer immunotherapy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33560199

RESUMO

A novel actinobacterium, designated strain NEAU-351T, was isolated from cow dung collected from Shangzhi, Heilongjiang Province, northeast PR China and characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-351T belonged to the genus Nocardia, with the highest similarity (98.96 %) to Nocardia takedensis DSM 44801T and less than 98.0 % identity with other type strains of the genus Nocardia. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major menaquinone was observed to contain MK-8(H4, ω-cycl) (78.2 %). The fatty acid profile mainly consisted of C16 : 0, C18 : 1 ω9c and 10-methyl C18 : 0. Mycolic acids were present. The genomic DNA G+C content of strain NEAU-351T was 68.1 mol%. In addition, the average nucleotide identity values between strain NEAU-351T and its reference strains, Nocardia takedensis DSM 44801T and Nocardia arizonensis NBRC 108935T, were found to be 81.4 and 82.9 %, respectively, and the level of digital DNA-DNA hybridization between them were 24.8 % (22.5-27.3 %) and 26.3 % (24-28.8 %), respectively. Here we report on the taxonomic characterization and classification of the isolate and propose that strain NEAU-351T represents a new species of the genus Nocardia, for which the name Nocardia bovistercoris is proposed. The type strain is NEAU-351T (=CCTCC AA 2019090T=DSM 110681T).

3.
Aging (Albany NY) ; 13(3): 3459-3482, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428606

RESUMO

Melanoma is a life-threatening form of skin cancer with an elevated risk of metastasis and high mortality rates. The prognosis and clinical outcomes of cancer immunotherapy in melanoma patients are influenced by immune cell infiltration in the tumor microenvironment (TME) and the expression of genetic factors. Despite reports suggesting that immune-classification may have a better prediction of prognosis compared to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM-classification, the definition of Immunoscore in melanoma is becoming a difficult challenge. In this study, we established and verified a 7-gene prognostic signature. Melanoma patients from the Cancer Genome Atlas (TCGA) were separated into a low-risk group and a high-risk group using the median risk score. Receiver operating characteristic (ROC) analysis for overall survival (OS) showed that the area under the curve (AUC) was 0.701 for 1 year, 0.726 for 3 years, and 0.745 for 5 years, respectively. Moreover, a nomogram was constructed as a practical prognostic tool, and the AUC was 0.829 for 3 years, and 0.803 for 5 years, respectively. Furthermore, we validated the above results in two datasets from the Gene Expression Omnibus (GEO) database and the relationship between 7-gene prognostic signature and immune infiltration estimated.

4.
Mol Cell ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33434504

RESUMO

STING-dependent cytosolic DNA sensing in dendritic cells (DCs) initiates antitumor immune responses, but how STING signaling is metabolically regulated in the tumor microenvironment remains unknown. Here, we show that oxidative stress is required for STING-induced DC antitumor function through a process that directs SUMO-specific protease 3 (SENP3) activity. DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon (IFN) signaling in DCs and dampening antitumor immune responses. DC-derived reactive oxygen species (ROS) trigger SENP3 accumulation and the SENP3-IFI204 interaction, thereby catalyzing IFI204 deSUMOylation and boosting STING signaling activation in mice. Consistently, SENP3 senses ROS to facilitate STING-dependent DC activity in tissue samples from colorectal cancer patients. Our results reveal that oxidative stress as a metabolic regulator promotes STING-mediated DC antitumor immune responses and highlights SENP3 as an overflow valve for STING signaling induction in the metabolically abnormal tumor microenvironment.

5.
Sci Rep ; 11(1): 2689, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514843

RESUMO

In order to study the influence of distance weight on ore-grade estimation, the inverse distance weighted (IDW) is used to estimate the Ni grade and MgO grade of serpentinite ore based on a three-dimensional ore body model and related block models. Manhattan distance, Euclidean distance, Chebyshev distance, and multiple forms of the Minkowski distance are used to calculate distance weight of IDW. Results show that using the Minkowski distance for the distance weight calculation is feasible. The law of the estimated results along with the distance weight is given. The study expands the distance weight calculation method in the IDW method, and a new method for improving estimation accuracy is given. Researchers can choose different weight calculation methods according to their needs. In this study, the estimated effect is best when the power of the Minkowski distance is 3 for a 10 m × 10 m × 10 m block model. For a 20 m × 20 m × 20 m block model, the estimated effect is best when the power of the Minkowski distance is 9.

6.
Biochem Biophys Res Commun ; 534: 134-140, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33341068

RESUMO

TIGIT is an emerging novel checkpoint target that is expressed on both tumor-infiltrating T cells and NK cells. Some current investigational antibodies targeting TIGIT have also achieved dramatic antitumor efficacy in late clinical research. Most recently, the relevance of NK cell-associated TIGIT signaling pathway to tumors' evasion of the immune system has been clearly revealed, which endows NK cells with a pivotal role in the therapeutic effects of TIGIT blockade. In this article, we describe a novel anti-TIGIT monoclonal antibody, AET2010, which was acquired from a phage-displayed human single-chain antibody library through a cell panning strategy. With emphasis on its regulation of NK cells, we confirmed the excellent ex vivo and in vivo antitumor immunity of AET2010 mediated by the NK-92MI cells. Intriguingly, our work also revealed that AET2010 displays a lower affinity but parallel avidity and activity relative to MK7684, an investigational monoclonal antibody from MSD, implying a reasonable balance of potency and potential side effects for AET2010. Together, these results are promising and warrant further development of AET2010.

7.
J Environ Sci (China) ; 101: 339-350, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33334528

RESUMO

The increase of electrical resistance (ER) and energy consumption (EC) during the later stage of dewatering is a major problem hindering the development of electro-dewatering (EDW) technology. As the variations of sludge characteristics are significant during the EDW process, the relationships between sludge characteristics and ER and EC during EDW remain unclear. In this study, the effects of moisture content (MC), thickness, pH, conductivity, zeta potential, temperature, and gas volume on the ER and EC during the EDW process were statistically investigated using correlation and multiple linear regression analyses. Herein, the results showed that the ER of the sludge near the anode was primarily affected by pH, whereas the sludge near the cathode was primarily affected by the MC and conductivity. Further, sludge temperature and conductivity were the most reliable indicators to predict the EC near the anode and cathode, respectively. The results of this study provide theoretical guidance useful for solving the increase of ER and EC during the later stage of the EDW process.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Condutividade Elétrica , Impedância Elétrica , Eletrodos , Água
8.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355624

RESUMO

Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell-specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell-derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1-PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function.

9.
Environ Res ; : 110453, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33188765

RESUMO

The high energy consumption of high apparent electrical resistivity (AER) in sludge during the later stages of the electro-dewatering (EDW) process is a difficult problem; however, analysis of sludge AER may contribute to a reduction in energy consumption. In this study, the variations in the AER of activated sludge and potential mechanisms related to sludge properties were systematically examined. First, a sludge cake was divided into four horizontal layers, in order to investigate the sludge AER in each layer. Then, the effects of variations in water distribution, oxidation-reduction potential (ORP), pH, metal ions, sludge conductivity, zeta potential, temperature, and sludge microstructure on the AER in each layer were explored. The results showed that the sludge AER began to increase from the bottom layers to the top layers when the moisture content (MC) was decreased to 60%. The formation of nonionic chemical systems and the gas barrier layer could increase the AER in the top layers, and the increase in sludge AER in the bottom layers was due to the decrease in MC and sludge conductivity. In addition, electrolyte release and electromigration had a significant effect on the sludge AER. This work identifies potential causes for the increase in AER, and provides a reference for solving problems related to high AER in sludge during the later stages of the EDW process.

10.
Biomed Res Int ; 2020: 2054293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195689

RESUMO

Background: The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. Methods: This study used RT-PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. Results: mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 µM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST's activity in hypoxia both in vivo and in vitro. Conclusions: Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.

11.
Front Psychol ; 11: 581397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250821

RESUMO

Grounded on the social exchange theory (SET), social cognitive theory (SCT), and self-determination theory (SDT), this study aims to explore the mediating role of self-efficacy (SE) and work engagement (WE) on the effect of social support (SS) on job satisfaction (JS) among Chinese ethnic minority kindergarten teachers (KTs). The results show that: (1) SS has a directly significant effect on JS; (2) WE mediates the relationship between SS and JS; and (3) SE mediates the relationship between SS and WE. Although the mediation of SE on the relationship between SS and JS is not found, the posited multiple mediations of SE and WE on the relationship between SS and JS are totally accepted. The results reveal that SS mainland Chinese ethnic minority KTs received can not only have a direct effect on JS but also have an indirect impact through the one-path mediating role of WE and the chain mediating role of SE and WE. The results suggest that governments, supervisors, and sponsors should work together to provide ethnic minority KTs with more prioritized SS from both cultural psychology and financial material and opportunities for facilitating professional knowledge and skills in order to enhance their SE, inspire their WE, and eventually accumulate their JS.

12.
Appl Opt ; 59(28): 9060-9066, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33104596

RESUMO

The ion-exchanged glasses bombarded with 80 eV, 100 eV, and 120 eV argon ions at room temperature are investigated. The optical and structural properties of ion-exchanged glasses before and after bombardment were analyzed by means of a UV-vis spectrometer, x-ray photoelectron spectroscopy, and electron probe micro analysis, respectively. The optical absorption and transmittance spectra of ion-exchanged glasses appear as obvious changes in the UV-visible region after bombardment. The optical absorption band and transmittance properties of ion-exchanged glasses at about 369-900 nm are less sensitive to the ion bombardment energy than that at about 200-280 nm. The changes in binding energy shift and peak area ratios of non-bridging oxygen and bridging oxygen contributions to the O 1s lines were observed with increasing ion beam bombardment energy. Accompanied with out-diffusion of potassium cations during argon ion bombardment, the peak of potassium cations concentration in the exchanged region decreases and moves into the interior of glasses in different degrees. The results show that variation of structure and optical properties of the ion-exchanged glasses are indicative of alterations of the silicate network structure induced by argon ion bombardment, which provide important information for application of the ion-exchanged glasses.

13.
Front Psychol ; 11: 2104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101103

RESUMO

Purpose: To understand the current pandemic, levels of anxiety in frontline staff, and whether they have been using medication to prevent COVID-19. Methods: Between January 10 and March 10, 2020, 290 frontline staff completed a questionnaire incorporating the Generalized Anxiety Disorder Scale 7 (GAD-7) to indicate their psychological behavior in the use of preventive medication. Results: Of those who participated in the study, 77.6% used preventive medication, with 47.5, 40.9, and 11.6% using these as part of routine preventive treatment, to fight infection after it was contracted, and after occupational exposure, respectively. There was a statistically significant relationship between the anxiety scale scores and the frequency of medication use (P < 0.05). Comparative analyses revealed that the scores of those in the group taking medication after occupational exposure (to respiratory and blood-borne pathogens) were significantly different from other groups. The proportion of participants choosing Western medicine, traditional Chinese medicine, and integrated Chinese and Western medicine was 24.4, 28.0, and 47.6%, respectively. Additionally, the relationship between the anxiety scale scores and the three types of medication was statistically significant (P < 0.05), as was the difference between Western medicine and other groups. According to Multinomial logistic regression based on the adjustment to gender, age, educational level, marital status, current workplace, and profession, participants with moderate to severe anxiety, had higher odds (OR = 10.331, 95%CI:1.453-73.429) of using Western medicine than participants with no anxiety. Participants with moderate anxiety were 6.399 times more likely to use an integrated combination of traditional Chinese and Western medicine compared to those with no anxiety (OR = 6.399, 95%CI:1.007-40.658). Furthermore, those with mild anxiety were 2.656 times more likely to use integrated traditional Chinese and Western medicine than those with no anxiety (OR = 2.657, 95%CI:1.075-6.570). The probability that frontline medical staff with moderate anxiety took preventive medication after occupational exposure to COVID-19 was 8.066 times (OR = 8.066, 95%CI:1.043-62.353) higher than that of staff without anxiety. Discussion: This study revealed that there was more anxiety among frontline medical staff who took medication after unexpected occupational exposure. There was less anxiety among those using an integrated course of Chinese and Western medicine than Western medicine alone. It was also observed that anxiety affects the types and frequency of the preventive medication taken. Frontline medical staff who suffer from anxiety are also more likely to use medication to prevent COVID-19.

14.
Chemosphere ; : 128609, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33092823

RESUMO

Coking wastewater is extremely toxic with poor biodegradability owing to the presence of refractory organics. Black titanium oxide nanotube array (BTN), not only photocatalyst but also electrocatalyst, is with definite potentiality in organic wastewater treatment. Here, we firstly developed an electrochemical method, using fluorinated coking wastewater as electrolyte rather than traditional fluorinated ethylene glycol, to prepare titanium oxide nanoarray economically. Unexpectedly, suspended pollutants and ammonia nitrogen in coking wastewater were removed in BTN preparation. Moreover, the as-prepared BTN could be further employed as photocatalyst or electrocatalyst to degrade dissolved organic matter in coking wastewater. As an electrocatalyst, BTN possessed the comparable •OH production activity about 9.9 × 10-15 M S-1 to boron-doped diamond, high oxygen evolution potential around 2.75 V, and high selectivity of chlorine production. Moreover, the biodegradability of treated coking wastewater could be effectively improved by using BTN as electrocatalyst in electrochemical oxidation, and the BOD/COD was from 0.19 to above 0.3 in 4 h at current density of 2 mA cm-2. The energy consumption was about 63-68 kWh kgCOD-1, lower than that of various reported electrodes. This study provided an economical and environmentally friendly method to prepare BTN, which was with positive application prospect in the field of coking wastewater treatment.

15.
J Microbiol ; 58(9): 812-820, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32870487

RESUMO

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32924237

RESUMO

AIMS: Low density lipoprotein receptor-related protein 6 (LRP6) has been demonstrated to control trophoblast cell invasion, but its regulatory gene remains undefined. In this study, microRNA (miR) regulating LRP6 were explored to elucidate the potential mechanism of preeclampsia (PE). METHODS: Firstly, the expression of LRP6 in PE tissues was detected by immunohistochemical staining and quantitative real-time polymerase chain reaction (qRT-PCR) assay. Prediction software predicted that LRP6 might be the target gene of miR-95-5p, and verified by double-luciferase reporter analysis. qRT-PCR assay measured the expression of miR-95-5p in PE tissues and trophoblast cell lines. Then, we transfected miR-95-5p mimic, inhibitor, LRP6, or mimic plus LRP6 into trophoblast cell lines, and analyzed their influences on cell migration and invasion by wound healing and Transwell experiments. The expressions of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-1 in transfected cells were examined by western blot (WB) analysis. RESULTS: LRP6 was low-expressed in PE tissues, while miR-95-5p expression was high-expressed. MiR-95-5p negatively regulated the LRP6 expression in trophoblast cells. Both up-regulated LRP6 and down-regulated miR-95-5p can not only promote the migration and invasion of trophoblast cells, but also raised the expressions of MMP-2 and MMP-9 and inhibited the expression of TIMP-1. The over-expression of miR-95-5p suppressed the metastasis of trophoblast cells and rescued LRP6-induced increase of MMP-2 and MMP-9 and reduction of TIMP-1. CONCLUSION: MiR-95-5p involved in the migration and invasion of trophoblast cells by targeting LRP6, which might be a potential therapeutic target for PE.

17.
Development ; 147(21)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32747436

RESUMO

Fragile X mental retardation protein (FMRP) is an RNA-binding protein abundant in the nervous system. Functional loss of FMRP leads to sensory dysfunction and severe intellectual disabilities. In the auditory system, FMRP deficiency alters neuronal function and synaptic connectivity and results in perturbed processing of sound information. Nevertheless, roles of FMRP in embryonic development of the auditory hindbrain have not been identified. Here, we developed high-specificity approaches to genetically track and manipulate throughout development of the Atoh1+ neuronal cell type, which is highly conserved in vertebrates, in the cochlear nucleus of chicken embryos. We identified distinct FMRP-containing granules in the growing axons of Atoh1+ neurons and post-migrating NM cells. FMRP downregulation induced by CRISPR/Cas9 and shRNA techniques resulted in perturbed axonal pathfinding, delay in midline crossing, excess branching of neurites, and axonal targeting errors during the period of circuit development. Together, these results provide the first in vivo identification of FMRP localization and actions in developing axons of auditory neurons, and demonstrate the importance of investigating early embryonic alterations toward understanding the pathogenesis of neurodevelopmental disorders.

18.
Front Public Health ; 8: 426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850610

RESUMO

Purpose: The current research on frontline medical staff in China fighting against COVID-19 has not yet addressed job satisfaction. The purpose of this study is to investigate the job satisfaction of those who were sent to support Hubei province, China, or worked in local designated hospitals, and then analyze the associated influencing factors. Materials and Methods: A total of 455 medical staff who worked at the frontline of the prevention and control of COVID-19 in Hubei province was selected using simple random sampling. They were asked to fill out a self-developed general information questionnaire as well as the Minnesota Satisfaction Questionnaire (MSQ), from 10 January to 10 March 2020. Results: The average job satisfaction score of the participants was 82.58 ± 11.11. The influencing factors include education (P = 0.002), years of work experience (P = 0.006), anti-epidemic work duration (P = 0.048), daily sleep duration (P < 0.001), and the form of participation (P < 0.001). Conclusions: This study, for the first time, measures the job satisfaction of frontline medical staff in fighting against COVID-19 in China. The job satisfaction of frontline medical staff was at a "relatively decent" level, higher than the previous similar measures among medical staff. Related management departments should further improve the job satisfaction of frontline medical staff by meeting their reasonable demands, strengthening the emergency response and practical operation training of junior staff, and ensuring their ample time for sleep and rest. This study is of great reference value for improving the job satisfaction level of frontline medical staff during public health emergencies, developing medical staff security policies, and promoting the establishment of emergency response teams.

19.
Environ Res ; 190: 110011, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32763282

RESUMO

Since the effect of electro-dewatering (EDW) on sludge water holding capacity was unknown, tests were conducted in this study to investigate the water holding capacity of EDW sludge and the potential mechanism related to the sludge physicochemical characteristics, EPS properties and sludge structure. Sludge was dewatered to the average moisture content (AMC) of 80%, 70% and 60% with different applied voltages at 20, 30 and 40V in EDW, respectively. Then the dewatered sludge near the anode and cathode were rewatered. The variation of sludge water holding capacity in EDW process was evaluated in terms of filterability and saturated moisture content (SMC), and the filterability was assessed by the specific resistance to filtration (SRF) of rewatered sludge. The results indicated that SRF of rewatered sludge near the cathode increased greatly. The proteins/polysaccharides (PN/PS) of loosely bound extracellular polymeric substances (LB-EPS) was significantly positively correlated with SRF (r = 0.891, p < 0.01). Moreover, the exposure of hydrophobic sites or groups in PN near the cathode improved the surface hydrophobicity of sludge, which reduced the filterability. In addition, higher voltage could destroy the sludge structure near the anode at the later stage of EDW process, leading to the decrease of SRF and SMC. These results expanded the knowledge about changes in sludge properties and water holding capacity during EDW process.

20.
Mol Oncol ; 14(10): 2589-2608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679610

RESUMO

Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms remain unclear. We identified a targeting relationship between tumor-suppressing miR-1255b-5p and human telomerase reverse transcriptase (hTERT) via clinical screening of serum samples in colorectal cancer (CRC) patients. EMT suppression via exosomal miR-1255b-5p delivery was investigated by assessing hTERT expression, Wnt/ß-catenin signaling, and telomerase activity. We revealed that hypoxia directly affected exosomal miR-1255b-5p content, the delivery of which between CRC cells significantly impacted cell invasion, EMT-related protein expression, and telomerase stability. Specifically, miR-1255b-5p suppressed EMT by inhibiting Wnt/ß-catenin activation via hTERT inhibition. Hypoxia reduced exosomal miR-1255b-5p secretion by CRC cells, thereby increasing hTERT expression to enhance EMT and telomerase activity. In a mouse CRC model, hypoxic exosomes containing overexpressed miR-1255b-5p attenuated EMT, tumor progression, and liver metastasis. Our results suggest the antitumor role of miR-1255b-5p and its involvement in the regulation of hTERT-mediated EMT. We propose that miRNA-targeted regulation of telomerase is a promising therapeutic strategy for future CRC treatment.

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