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PURPOSE: This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. METHODS: Pediatric patients under 18 years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. RESULTS: Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13 years (range 3 years and 5 months-17 years and 9 months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. CONCLUSIONS: Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3 years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP.
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Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Feminino , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Retrospectivos , Criança , Pré-Escolar , Adolescente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pancreatite/etiologia , Pancreatite/epidemiologia , Lactente , Estudos de ViabilidadeRESUMO
Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.
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Lithium metal batteries (LMBs) using Li metals as anodes are conspicuous for high-energy-density energy-storage devices. However, the nonuniform deposition of Li+ ions leading to uncontrolled Li dendrite growth, which adversely affects electrochemical performance and safety, has impeded the practical application of lithium metal batteries (LMBs). Herein, PIM-1, a type of polymer of intrinsic microporosity (PIM), was utilized for surface engineering of conventional polyolefin separators. This process resulted in the formation of a continuous and homogeneous coating across the separator, facilitating uniform Li+ ion flux and deposition, and consequently reducing dendrite formation. Notably, the loading mass was quite low (0.6 g/m2) through the convenient dipping method. The intrinsic micropores and polar groups (cyano and ether groups) of PIM-1 greatly improved the electrolyte wettability and ionic conductivity of commercial polypropylene (PP) separators. And the PIM-1 coating guided Li+ flux to achieve uniform Li deposition. Moreover, the polar groups (cyano and ether groups) of PIM-1 are beneficial to the desolvation of Li+-solvates. As a result, the synergetic effect of uniform Li+ flux, desolvation, and enhanced mechanical strength of separators brings about considerable improvement in cycle life, suppression of Li dendrite, and Coulombic efficiency for LMBs. As this surface engineering is simple, relatively low-cost, and effective, this work provides fresh insights into separators for LMBs.
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This study focused on exploring the effect of peroxydisulfate (PDS) on the regulation of reactive species during water radiolysis process and its potential application for degrading organic pollutants. The results indicated that PDS was successfully activated by ionizing radiation for efficient removal of three typical phenolic compounds over a wide pH range (3.0â¼12.0) at absorbed dose of 5 kGy. Chemical probe methods provided the evidence that the addition of PDS could introduce the sulfate radicals (SO4â¢-) and enhance the production of hydroxyl radicals (â¢OH). According to the quenching tests, â¢OH and SO4â¢- were the dominant reactive species responsible for the degradation of 4-NP, while hydrated electron (eaq-) played a minor role. The regulatory effect of PDS on active species in the ionizing radiation process could divided by (i) PDS could be directly activated by ionizing radiation to produce â¢OH and SO4â¢- via energy transfer pathway; (ii) PDS could boost the conversion of eaq- to SO4â¢- via electron transfer pathway. Furthermore, we assessed the applicability of the IR and IR/PDS systems in treating mixed solutions containing various pollutants and actual coking wastewater.
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Antibiotic fermentation residue, which is generated from the microbial antibiotic production process, has been a troublesome waste faced by the pharmaceutical industry. Dark fermentation is a potential technology to treat antibiotic fermentation residue in terms of renewable H2 generation and waste management. However, the inherent antibiotic in antibiotic fermentation residue may inhibit its dark fermentation performance, and current understanding on this topic is limited. This investigation examined the impact of the inherent antibiotic on the dark H2 fermentation of Cephalosporin C (CEPC) fermentation residue, and explored the mechanisms from the perspectives of bacterial communities and functional genes. It was found that CEP-C in the antibiotic fermentation residue significantly inhibited the H2 production, with the H2 yield decreasing from 17.2 mL/g-VSadded to 12.5 and 9.6 mL/g-VSadded at CEP-C concentrations of 100 and 200 mg/L, respectively. CEP-C also prolonged the H2-producing lag period. Microbiological analysis indicated that CEP-C remarkably decreased the abundances of high-yielding H2-producing bacteria, as well as downregulated the genes involved in hydrogen generation from the"pyruvate pathway" and"NADH pathway", essentially leading to the decline of H2 productivity. The present work gains insights into how cephalosporin antibiotics influence the dark H2 fermentation, and provide guidance for mitigating the inhibitory effects.
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Antibacterianos , Cefalosporinas , Fermentação , Hidrogênio , Hidrogênio/metabolismo , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Bactérias/metabolismo , Bactérias/efeitos dos fármacosRESUMO
Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.
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Glucose Oxidase , Hiperglicemia , Óxido Nítrico , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Animais , Glucose Oxidase/metabolismo , Humanos , Camundongos , Glucose/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Further reducing total nitrogen (TN) and total phosphorus (TP) in the secondary effluent needs to be realized effectively and in an eco-friendly manner. Herein, four pyrite/sawdust composite-based biofilters were established to treat simulated secondary effluent for 304 days. The results demonstrated that effluent TN and TP concentrations from biofilters under the optimal hydraulic retention time (HRT) of 3.5 h were stable at <2.0 and 0.1 mg/L, respectively, and no significant differences were observed between inoculated sludge sources. The pyrite/sawdust composite-based biofilters had low N2O, CH4, and CO2 emissions, and the effluent's DOM was mainly composed of five fluorescence components. Moreover, mixotrophic denitrifiers (Thiothrix) and sulfate-reducing bacteria (Desulfosporosinus) contributing to microbial nitrogen and sulfur cycles were enriched in the biofilm. Co-occurrence network analysis deciphered that Chlorobaculum and Desulfobacterales were key genera, which formed an obvious sulfur cycle process that strengthened the denitrification capacity. The higher abundances of genes encoding extracellular electron transport (EET) chains/mediators revealed that pyrite not only functioned as an electron conduit to stimulate direct interspecies electron transfer by flagella but also facilitated EET-associated enzymes for denitrification. This study comprehensively evaluates the water-gas-biofilm phases of pyrite/sawdust composite-based biofilters during a long-term study, providing an in-depth understanding of boosted electron transfer in pyrite-based mixotrophic denitrification systems.
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Biofilmes , Desnitrificação , Nitratos , Fósforo , Fósforo/metabolismo , Nitratos/metabolismo , Nitrogênio/metabolismo , Transporte de Elétrons , Ferro , SulfetosRESUMO
In this study, ionizing radiation was used to induce the in-situ formation of highly dispersed nanosized cobalt oxide on the surface of graphene oxide (R-Co-GO), which was highly effective for activating PMS to degrade sulfamethoxazole (SMX). R-Co-GO had the highest catalytic activity when 150 µL cobalt chloride hexahydrate solution was used in the precursor, and the pseudo first-order kinetic constant of SMX degradation was 0.07 min-1 with high mineralization efficiency (63.1 %) and high PMS utilization efficiency. The sulfate radicals and high-valent cobalt oxo were mainly responsible for SMX degradation. Mechanism analysis showed that cobalt active site dominated in PMS activation, which was responsible for the formation of sulfate radicals and high-valent cobalt oxo; while the carbon framework contributed to the formation of singlet oxygen. The R-Co-GO-150 had good catalytic activity and stability in five cycling experiments, in which SMX was completely degraded and the concentration of dissolved Co was below 0.1 mg/L. In addition, the R-Co-GO-150/PMS system could also degrade phenol, bisphenol A, atrazine and nitrobenzene effectively, confirming its wide applicability. This study provided a facile method to uniformly disperse the metal oxides on the surface of carbon materials, and an effective system for the removal of emerging organic pollutants from the actual wastewater.
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Ionizing radiation (mainly including gamma ray and electron beam) technology provides a more efficient and ecological option for dye-containing wastewater treatment, which is supported by its successful achievements in industrial-scale applications. However, the degradation pathway of triphenylmethane dyes by radiation technology is still unclear. In this study, crystal violet (CV) was selected as representative cationic triphenylmethane dye, the decolorization and degradation performance by electron beam radiation technology was systematically evaluated. The results showed that CV can be efficiently decolorized and mineralized by radiation, and its degradation kinetics followed the first-order kinetic model. The effect of inorganic anions and chelating agents commonly existed in dye-containing wastewater on CV decolorization and total organic carbon (TOC) removal was explored. Quenching experiments, density functional theory (DFT) calculation and high performance liquid chromatography mass spectrometry (HPLC-MS) analysis were employed to reveal CV decolorization and degradation mechanism and pathway, which mainly included N-demethylation, triphenylmethane chromophore cleavage, ring-opening of aromatic products and further oxidation to carboxylic acid, and mineralization to CO2 and H2O. Additionally, electron beam radiation/PMS process was explored to decrease the absorbed dose required for decolorization and degradation, and the synergetic effect of radiation with PMS was elucidated. More importantly, the findings of this study would provide the support for treating actual dyeing wastewater by electron beam radiation technology.
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Violeta Genciana , Águas Residuárias , Poluentes Químicos da Água , Violeta Genciana/química , Poluentes Químicos da Água/química , Águas Residuárias/química , Corantes/química , Peróxidos/química , Eliminação de Resíduos Líquidos/métodos , Descoloração da Água/métodos , Elétrons , CinéticaRESUMO
ABSTRACT: The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because of the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor growth arrest and DNA damage-inducible 45 alpha (GADD45A) is implicated in poor clinical outcomes, but its role in LSCs and AML pathogenesis is unknown. Here, we define GADD45A as a key downstream target of G protein-coupled receptor (LGR)4 pathway and discover a regulatory role for GADD45A loss in promoting leukemia-initiating activity and oxidative resistance in LGR4/HOXA9-dependent AML, a poor prognosis subset of leukemia. Knockout of GADD45A enhances AML progression in murine and patient-derived xenograft (PDX) mouse models. Deletion of GADD45A induces substantial mutations, increases LSC self-renewal and stemness in vivo, and reduces levels of reactive oxygen species (ROS), accompanied by a decreased response to ROS-associated genotoxic agents (eg, ferroptosis inducer RSL3) and acquisition of an increasingly aggressive phenotype on serial transplantation in mice. Our single-cell cellular indexing of transcriptomes and epitopes by sequencing analysis on patient-derived LSCs in PDX mice and subsequent functional studies in murine LSCs and primary AML patient cells show that loss of GADD45A is associated with resistance to ferroptosis (an iron-dependent oxidative cell death caused by ROS accumulation) through aberrant activation of antioxidant pathways related to iron and ROS detoxification, such as FTH1 and PRDX1, upregulation of which correlates with unfavorable outcomes in patients with AML. These results reveal a therapy resistance mechanism contributing to poor prognosis and support a role for GADD45A loss as a critical step for leukemia-initiating activity and as a target to overcome resistance in aggressive leukemia.
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Proteínas de Ciclo Celular , Ferroptose , Leucemia Mieloide Aguda , Células-Tronco Neoplásicas , Animais , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Camundongos , Humanos , Ferroptose/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Camundongos Knockout , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteínas GADD45RESUMO
Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit the activity of both AR and GR. Herein, we optimized the structure of Z19 and identified GA32 as a potent AR/GR dual inhibitor. GA32 efficiently reduced the mRNA and protein levels of AR/GR downstream genes. GA32 efficiently inhibited the proliferation of enzalutamide resistance CRPC both in vitro and in vivo. GA32 could directly bind to AR and GR, and the predicted binding modes for GA32 with AR/GR suggested that GA32 binds to the AR or GR hormone binding pocket. This work provides a potential lead compound with dual AR/GR inhibitory activity to conquer the drug resistance of CRPC.
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Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores de Glucocorticoides/metabolismo , Resistencia a Medicamentos Antineoplásicos , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Nitrilas/uso terapêutico , Linhagem Celular TumoralRESUMO
BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. PURPOSE: Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. METHODS: First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. RESULTS: A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. CONCLUSION: A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.
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Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Algoritmos , Linhagem CelularRESUMO
The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates epiblast development in vivo during the peri-implantation period of mouse embryo development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events that occur during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knockin cell models, we identify the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, which is dependent on the formation of R-loops in ZFP281-targeted gene promoters, undergoes a "high-low-high" bimodal pattern regulating dynamic DNA methylation and gene expression during the naive-formative-primed transitions. ZFP281 also safeguards DNA methylation in maintaining primed pluripotency. Our study demonstrates a previously unappreciated role for ZFP281 in coordinating DNMT3A/3B and TET1 functions to promote pluripotent state transitions.
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Epigênese Genética , Células-Tronco Pluripotentes , Animais , Camundongos , Metilação de DNA/genética , Cromatina/metabolismo , DNA/metabolismo , Diferenciação Celular/genética , Camadas Germinativas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismoRESUMO
The management of wastewater produced from alkali/surfactant/polymer (ASP) flooding, known for its considerable volume and high emulsion stability, poses a challenge in oilfields globally. This study has demonstrated that ionizing irradiation is a promising pretreatment method for ASP wastewater to improve oil-water separation. After a settling time of 1 h, approximately 69.5% of oil remained in the raw ASP wastewater, while only 20-29% of the oil persisted in the liquid phase following radiation at absorbed doses ranging from 0.1 to 5.0 kGy. A noticeable increase in the size of oil droplets and reduction in turbidity was observed after irradiation. Further analysis revealed that the combination of surfactant, sodium dodecyl sulfate (SDS) and alkali exhibits a synergistic impact, leading to a substantial reduction in interface tension of ASP wastewater. Notably, ionizing irradiation induces several key changes that are crucial for efficient demulsification. The transformation of the wastewater's rheological behavior from pseudoplastics to a Newtonian fluid accompanied by a reduction in viscosity, the increased interfacial tension at both liquid-air and liquid-oil interfaces, along with the degradation of organic components such as partly hydrolyzed polyacrylamide (HPAM) and SDS, all contribute to the coalescence and floatation of oil droplets.
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Elétrons , Águas Residuárias , Polímeros , Tensoativos , Água , ÁlcalisRESUMO
The treatment of dye-containing wastewater generated from textile industries is still a challenge, and various technologies, including physical, chemical and biological ones have been used. In recent years, the ionizing radiation (usually including gamma ray generated by radionuclide, such as 60Co and 137Cs, and electron beam generated by electron accelerator) technology has received increasing attention for degrading refractory or toxic organic pollutants in wastewater because of its unique advantages, such as no chemical additives, fast reaction rate, strong degradation capacity, high efficiency, flexibility, controllability. Compared to the conventional wastewater treatment processes, ionizing radiation technology, as a disruptive wastewater treatment technology, is more efficient for the decolorization and degradation of dyes and the treatment of dye-containing wastewater. In this paper, the recent advances in the treatment of dye-containing wastewater by ionizing radiation, in particular by electron beam (EB) radiation were summarized and analyzed, focusing on the decolorization and degradation of various dyes. Firstly, the formation of various reactive species induced by radiation and their interactions with dye molecules, as well as the influencing factors on the removal efficiency of dyes were discussed. Secondly, the researches on the treating dye-containing wastewater by electron beam radiation technology were systematically reviewed. Then, the decolorization and degradation mechanisms by electron beam radiation were further discussed in detail. And the integrated processes that would contribute to the advancement of this technology in practical applications were examined. More importantly, the recent advances of electron beam radiation technology from laboratory to application were reviewed, especially successful operation of dye-containing wastewater treatment facilities in China. And eventually, current challenges, future research directions, and outlooks of electron beam radiation technology were proposed for further advancing this technology for the sustainable development of water resources.
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Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Corantes/química , Elétrons , Radiação Ionizante , Poluentes Químicos da Água/análise , Compostos Azo/químicaRESUMO
There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.
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Neoplasias Ósseas , Osteossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Prognóstico , Sarcoma/genética , Sarcoma/terapia , Osteossarcoma/genética , Osteossarcoma/terapia , ImunoterapiaRESUMO
Background: Cholangiocarcinoma is a primary malignant tumor, and its progression involves oncogene activation, the absence of tumor suppressor gene, abnormal signaling pathways and miRNA expression. MiRNAs are abnormally expressed in many types of tumors. Objective: This study aims to observe the effects of miR-582 on cholangiocarcinoma cell proliferation, S-phase arrest, migration and invasion and to analyze the regulation of miR-582 on LIS1 to clarify the real role of miR-582 in cholangiocarcinoma development. Materials and Methods: TCGA database of cholangiocarcinoma samples was analyzed. Dual fluorescence reporter and TargetScan were conducted to confirm whether LIS1 was the target gene of miR-582. Effects of miR-582 and LIS1 on HCC-9810 cell proliferation, S-phase cell ratio, migration and invasion were determined by CCK-8, Flow cytometry and Transwell, respectively, whereas the function of miR-582 on MMP-2 and P-Akt expression was identified by Western blotting. Nude mice xenograft model of cholangiocarcinoma was established to detect what miR-582 did for tumor growth. Results: TCGA showed that miR-582 was lowly expressed and LIS1 was highly expressed in tumor tissues compared with adjacent tissues. MiR-582 targeted LIS1 to inhibit MMP-2 and p-AKT expression. Transfection of miR-582 mimics could suppress HCC-9810 cell proliferation, S-stage arrest, migration and invasion, while LIS1 worked oppositely. MiR-582 inhibitors promoted cell biological behavior, whereas LIS1 siRNA was opposite. In nude mice xenograft model, miR-582 overexpression inhibited tumor growth. Conclusions: It implies that miR-582 could negatively regulate LIS1 to inhibit MMP-2 and P-Akt expression, thus suppressing cell invasion and proliferation in cholangiocarcinoma.