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BACKGROUND AND AIM: Lipid metabolism disorder is the primary feature of numerous refractory chronic diseases. Fatty acid oxidation, an essential aerobic biological process, is closely related to the progression of NAFLD. The forkhead transcription factor FOXO1 has been reported to play an important role in lipid metabolism. However, the molecular mechanism through which FOXO1 regulates fatty acid oxidation remains unclear. METHODS: Transcriptomic analysis was performed to examine the cellular expression profile to determine the functional role of FOXO1 in HepG2 cells with palmitic acid (PA)-induced lipid accumulation. FOXO1-binding motifs at the promoter region of aldehyde dehydrogenase 1 family member L2 (ALDH1L2) were predicted via bioinformatic analysis and confirmed via luciferase reporter assay. Overexpression of ALDH1L2 was induced to recover the impaired fatty acid oxidation in FOXO1-knockout cells. RESULTS: Knockout of FOXO1 aggravated lipid deposition in hepatic cells. Transcriptomic profiling revealed that knockout of FOXO1 increased the expression of genes associated with fatty acid synthesis but decreased the expression of carnitine palmitoyltransferase1a (CPT1α) and adipose triglyceride lipase (ATGL), which contribute to fatty acid oxidation. Mechanistically, FOXO1 was identified as a transcription factor of ALDH1L2. Knockout of FOXO1 significantly decreased the protein expression of ALDH1L2 and CPT1α in vitro and in vivo. Furthermore, overexpression of ALDH1L2 restored fatty acid oxidation in FOXO1-knockout cells. CONCLUSION: The findings of this study indicate that FOXO1 modulates fatty acid oxidation by targeting ALDH1L2.
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BACKGROUND AND AIMS: Mitochondrial dysfunction plays a crucial role in the progression of non-alcoholic steatohepatitis (NASH). Mitochondrial division inhibitor 1 (Mdivi1) is a potential inhibitor of dynamin-related protein (Drp1) and mitochondrial fission. However, the therapeutic effect of Mdivi1 against NASH and its underlying molecular mechanisms remain unclear. METHODS: In this study, we established mouse models of NASH by inducing high-fat/high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diets and treated the animals with 5 mg/kg/day Mdivi1 or placebo. RESULTS: Treatment with Mdivi1 significantly alleviated diet-induced fatty liver phenotypes, including increased liver weight/body weight ratio, insulin resistance, hepatic lipid accumulation, steatohepatitis, and liver injury. Furthermore, Mdivi1 treatment suppressed HFHC or MCD diet-induced changes in the expression of genes related to lipid metabolism and inflammatory cytokines. Additionally, Mdivi1 reduced macrophage infiltration in the injured liver and promoted polarization of macrophages towards the M1 phenotype. At the molecular level, Mdivi1 attenuated mitochondrial fission by reducing Drp1 activation and expression, thereby decreasing mitochondrial reactive oxygen species accumulation and mitochondrial DNA damage. Moreover, Mdivi1-treated mice exhibited elevated levels of phosphorylated-c-Jun N-terminal kinase (p-JNK), mitochondrial fission factor (MFF), cleaved caspase 3 protein, and TUNEL-positive cell expression in the liver, suggesting that Mdivi1 might ameliorate mitochondrial dysfunction and reduce hepatocyte apoptosis by inhibiting the JNK/MFF pathway. CONCLUSION: Collectively, Mdivi1 protected against diet-induced NASH by restoring mitochondrial homeostasis and function, potentially through its inhibitory effect on the JNK/MFF pathway. Consequently, further investigation of Mdivi1 as a promising drug for NASH treatment is warranted.
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Doenças Mitocondriais , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Citocinas/metabolismo , Mitocôndrias/metabolismo , Fatores de Transcrição/metabolismo , Colina/metabolismo , Dinaminas , Doenças Mitocondriais/metabolismo , Camundongos Endogâmicos C57BL , Metionina , Modelos Animais de DoençasRESUMO
OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.
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Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Artéria Hepática , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
Rice consumption is a major dietary source of human exposure to arsenic (As), with As bioavailability being an important factor influencing its health risk. In this study, the As bioaccessibility was measured in 11 rice grains (140-335 µg As kg-1), which were compared to As relative bioavailability previously measured based on a mouse bioassay (Li et al., 2017). Using modified physiologically-based extraction test for rice (MPBET), As bioaccessibility in raw rice samples (44-88% in the gastric phase and 47-102% in the intestinal phase) was similar to those in cooked rice (42-73% and 43-99%). Arsenic bioaccessibility in rice was generally higher in the intestinal phase than in the gastric phase, with Fe and Ca concentrations in rice being negatively correlated with As bioaccessibility in the gastric phase (R2 = 0.47-0.49). In addition, for cooked rice, strong positive correlation was observed between bioaccessible As and inorganic As (R2 = 0.63-0.72), suggesting inorganic As in rice was easier to dissolve than organic As in gastrointestinal digestive fluids. Due to limited variation in As bioaccessibility and As bioavailability among the 11 samples, a weak correlation was observed between them (R2 = 0.01-0.03); however, As bioaccessibility values measured by the gastric phase (GP) of the MPBET agreed with As bioavailability values based on a mouse bioassay, suggesting the potential of the MPBETGP to predict As bioavailability in rice. Future work is needed to ascertain the robustness of the MPBETGP in predicting As bioavailability in rice using additional samples.
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Arsênio , Oryza , Poluentes do Solo , Arsênio/análise , Disponibilidade Biológica , Culinária , MineraisRESUMO
The application of nano-level passivating agents in the remediation of soil heavy metal pollution has received widespread attention, but its harm to soil animals should also be addressed. This study explored the effect of three nanomaterials-nanohydroxyapatite apatite (n-HAP), nano zeolite (n-zeolite), and nanometer iron oxide (n-Fe3O4), on catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content through filter paper contact test. The effects of nanomaterials spiked at 1.5%wt of soils on earthworm avoidance behavior were also be studied, and the crystallinity and surface charge of three nanomaterials were characterized. The results showed that the activities of CAT, SOD and POD and the content of MDA have been changed at different level. And earthworms have obvious avoidance behavior to the three kinds of nanomaterials. Therefore, nanomaterials do have adverse effects on earthworms, and their biological toxicity should be considered when selecting passivating agents for soil heavy metal pollution remediation.
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Aprendizagem da Esquiva/efeitos dos fármacos , Recuperação e Remediação Ambiental/métodos , Reação de Fuga/efeitos dos fármacos , Nanoestruturas/toxicidade , Oligoquetos/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/química , Animais , Catalase/metabolismo , Malondialdeído/metabolismo , Nanoestruturas/química , Oligoquetos/metabolismo , Peroxidase/metabolismo , Poluentes do Solo/química , Superóxido Dismutase/metabolismoRESUMO
Little is known about the effect of modified carbon black nanoparticles (MNCB) on the availability of heavy metals and petroleum degradation in petroleum and heavy metals co-contaminated soils. The overall objective of this study was to investigate the simultaneous effect of MNCB on heavy metal immobilization and petroleum biodegradation in co-contaminated soil in plant and plant-microbe combined remediation. The results showed that the petroleum degradation increased by 50% in petroleum-Cd co-contaminated soil and 65% in petroleum-Ni co-contaminated soil in plant-microbe combined remediation, comparing with the plant remediation and the application of MNCB did not show significant improvement on petroleum degradation in both plant and plant-microbe combined remediation. MNCB could significantly reduce the availability of heavy metals in soil and the uptakes of Cd and Ni by Suaeda salsa by roughly 18 and 10% and improve the growth of plant by alleviating the growth inhibition caused by heavy metals. The application of Bacillus subtilis and Sphingobacterium multivorum (heavy metal tolerant bacteria) inhibited the biomass of Suaeda salsa by enhancing the petroleum degradation. It could be concluded that MNCB played a major role in immobilizing the heavy metals and bacteria dominated the petroleum degradation in petroleum-metal co-contaminated soil.
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Metais Pesados , Nanopartículas , Petróleo , Poluentes do Solo , Biodegradação Ambiental , Solo , FuligemRESUMO
Engineered nanomaterials (NMs) may enter the soil through various channels and pose potential harm to soil animals, especially those proactively applied for soil heavy metal remediation. Effects of nano-carbon black (CB) and surface modified carbon black (MCB) on catalase (CAT) activity and malondialdehyde (MDA) content in earthworms exposed on filter paper for 48 h were tested. Avoidance test was used to determine hazard of soil treated with 0.015% and 1.5% CB and MCB. Surface properties of NMs were also characterized. MCB has a significant effect on CAT activity at 70 and 1000 mg/L (1.1 and 15.7 µg/cm2), but has no impact on MDA content in earthworm. Strongly avoidance behavior of worms was also found in soil added 1.5% MCB. Negative charges and oxygen functional groups increased for MCB and its adverse effect on earthworm was higher than CB. The application of MCB in soil remediation warrants more attention.
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Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Fuligem/toxicidade , Animais , Malondialdeído , Oligoquetos/efeitos dos fármacos , Solo , Poluentes do Solo/análiseRESUMO
Batch experiments were conducted to evaluate fluoride removal by Al, Fe, and Ti-based coagulants and adsorbents, as well as the effects of coexisting ions and formation of aluminum-fluoride complexes on fluoride removal by co-precipitation with alum (Al2(SO4)3·18H2O). Aluminum sulfate was more efficient than the other coagulants for fluoride removal in the pH range between 6 and 8. Nano-crystalline TiO2 was more effective for fluoride removal than Al and Fe hydroxides in a pH range of 3-5. Coexisting anions in water decreased the removal of fluoride in the order: phosphate (2.5mg/L)>arsenate (0.1mg/L)>bicarbonate (200mg/L)>sulfate (100mg/L)=nitrate (100mg/L)>silicate (10mg/L) at a pH of 6.0. The effect of silicate became more significant at pH>7.0. Calcium and magnesium improved the removal of fluoride. Zeta-potential measurements determined that the adsorption of fluoride shifted the PZC of Al(OH)3 precipitates from 8.9 to 8.4, indicating the chemical adsorption of fluoride at the surface. The presence of fluoride in solution significantly increased the soluble aluminum concentration at pH<6.5. A Visual MINTEQ modeling study indicated that the increased aluminum solubility was caused by the formation of AlF2+, AlF2+, and AlF3 complexes. The AlFx complexes decreased the removal of fluoride during co-precipitation with aluminum sulfate.
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Fluoretos/química , Modelos Químicos , Poluentes Químicos da Água/química , Alumínio/química , Fluoretos/análise , Ferro/química , Titânio/química , Poluentes Químicos da Água/análise , Purificação da Água/métodosRESUMO
The aim of this study was to evaluate the therapeutic efficacy and the safety of transarterial infusion (TAI) with gemcitabine and oxaliplatin in patients with unresectable pancreatic cancer (PC). After celiac arteriogram and super-mesenteric arteriography, 1000 mg/m gemcitabine and 100 mg/m oxaliplatin were infused through 4- or 5-Fr catheters in arteries supplying blood to the tumor. In cases in which the blood-supplying artery could be selectively catheterized, the infusion was performed through a 3-Fr catheter placed in the tumor-supplying artery. Therapeutic courses were repeated every 4 weeks. The tumor response, the overall survival, and adverse effects were monitored. Thirty-two patients with unresectable PC were enrolled in this study, including 20 male and 12 female patients. A total of 105 cycles of TAI (mean=3.3 cycles/patient) were performed. Of 32 patients, partial remission was achieved in eight (25.0%), stable disease in 13 (40.6%), and progressive disease in 11 (34.4%). The overall response rate was 25.0%. The median survival time was 10.0 months (range=4-21 months). Grade III-IV toxicity, vomiting, occurred with a rate of 21.9%. Grade I-II neutropenia, thrombocytopenia, peripheral nerve toxicity, elevated serum transaminases levels, and serum total bilirubin were observed. TAI with gemcitabine and oxaliplatin is well tolerated and highly effective in patients with unresectable PC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Feminino , Artéria Femoral , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
BACKGROUND: Stent occlusion by tumor ingrowth or overgrowth is the main cause of jaundice recurrence after metal stent insertion in patients with malignant obstructive jaundice (MOJ). The application of intraluminal brachytherapy (ILBT) in patients with MOJ results in local control of malignant tumors, which prolong stent patency. PURPOSE: To evaluate the safety of ILBT in pig bile ducts using ribbons of iodine-125 ((125)I) seeds. MATERIAL AND METHODS: Sixteen healthy pigs were randomly assigned to four groups of four pigs each. A (125)I seed ribbon was implanted into the common bile duct of each animal through an incision in the duct wall, and was fixed by suturing. The four groups of animals were sacrificed at 15, 30, 60, and 120 days after ribbon implantation, respectively. Serum bilirubin concentrations, alanine aminotransferase concentrations, and white blood cell counts before and after implantation were compared within each group. Pathological changes to the bile duct wall were observed using a light microscope. Morphological changes in biliary epithelial cells and organelles were observed with electron microscopy. RESULTS: (125)I ribbons were successfully implanted in all animals without surgery-related death. We found no significant difference in pre- and post-implant serum bilirubin, alanine aminotransferase, or white blood cell counts. Light and electron microscopy showed that the most severe bile duct damage occurred in the 15-day group, which exhibited necrosis and detachment of numerous epithelial cells, and infiltration of inflammatory cells. Repair and proliferation of the bile duct epithelium began 30 days after implantation and was nearly complete at 60 days. CONCLUSION: This study demonstrated the safety of ILBT using a (125)I ribbon in the pig bile duct. (125)I seed ribbons may be used in the treatment of MOJ in humans.
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Alanina Transaminase/sangue , Braquiterapia/efeitos adversos , Ducto Colédoco/efeitos da radiação , Radioisótopos do Iodo/efeitos adversos , Icterícia Obstrutiva/radioterapia , Animais , Bilirrubina/sangue , Modelos Animais de Doenças , Contagem de Leucócitos , Distribuição Aleatória , SuínosRESUMO
BACKGROUND: Liver biopsy is the "gold standard" for evaluating liver disorders, but controversies over the potential risk of complications and patient discomfort still exist. Using a 21G fine needle, we developed a new biopsy procedure, fine needle aspirating and cutting (FNAC). Our procedure obtains enough tissue for pathological examination and meanwhile, reduces the risk of biopsy complications. The present study was to determine the safety and efficiency of 21G FNAC compared with 18G Tru-cut core needle (TCN) in liver tumor biopsies. METHODS: Ninety-four patients with unresectable malignant tumors were included in this study. Patients were divided into 2 groups: 18G TCN and 21G FNAC. The total positive rate (TPR) and safety of both groups were compared. RESULTS: TPR was not different between the two groups. Liver puncture track subcapsular hemorrhage and arteriovenous shunt were reported with 18G TCN but not with 21G FNAC. The incidence of pain caused by biopsy was higher for the 18G TCN group compared to the 21G FNAC group (P<0.05). About 82.6% of the patients in the 18G TCN group had a sample length >0.5 cm, but 52.1% in the 21G FNAC group (P<0.05). More than 50% of patients in both groups had sufficient tissue for immunohistochemical examination. CONCLUSIONS: TPR is not different between the 21G FNAC and 18G TCN biopsy procedures, but the safety of 21G FNAC is superior to that of 18G TCN. Tissues obtained by either of these two procedures are sufficient for a pathological diagnosis.
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Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Neoplasias Hepáticas/patologia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina/efeitos adversos , Biópsia com Agulha de Grande Calibre/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Valor Preditivo dos Testes , Adulto JovemRESUMO
Reducing the mobility and bioavailability of heavy metals in soils by adding exogenous materials is a technology for remediating soils contaminated with heavy metals. Unlike industrial sites, the use of such techniques in agricultural soils requires consideration of not only reducing the mobility of heavy metals but also avoiding adverse effects on soil fertility and the growth of plants. Due to the uncertainty of the stability of amendments applied to agricultural soil, the application of amendments in farmland soil is controversial. This article reviewed the field studies in which amendments were used to immobilize heavy metals, and identified the potential environmental impacts of all aspects of soil amendment usage, including production and processing, transportation, storage, application to soil, long-term stability, and plant absorption. Results of the study indicated that after identifying the environmental risks of the whole process of the application of improvers in agricultural fields, it is necessary to classify the risks according to their characteristics, and design differentiated risk control measures for the safe application of this type of technology.
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Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Solo , Poluentes do Solo/análise , Metais Pesados/análise , Plantas , Disponibilidade BiológicaRESUMO
Commercial nano-scale carbon blacks (CB) are being harnessed widely and may impose potentially hazardous effects because of their unique properties, especially if they have been modified to grow reactive functional groups on their surface. Cytotoxicity of CB has been well studied but the membrane damage mechanisms and role of surface modification are still open to debate. Negatively and positively charged giant unilamellar vesicles (GUVs) were prepared using three lipids as model cell membranes to examine the mechanistic damage of CB and MCB (modified by acidic potassium permanganate) aggregates. Optical images showed that both anionic CB and MCB disrupted the positively charged but not the negatively charged GUVs. This disruption deteriorated with the rise and extension of exposure concentration and time. Lipids extraction caused by CBNs (CB and MCB together are called CBNs) was found. MCB caused more severe disruption than CB. MCB was enveloped into vesicles through an endocytosis-like process at 120 mg/L. MCB mediated the gelation of GUVs, perhaps through C-O-P bonding bridges. The lower hydrodynamic diameter and more negative charges may have been responsible for the distinction effect of MCB over CB. The adhesion and bonding of CBNs to the membrane were favored by electrostatic interaction and the practical application of CBNs warrants more attention.
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Nanopartículas , Fosfolipídeos , Fuligem , Membrana CelularRESUMO
Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.
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Cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs) are prominent soil contaminants found in industrial sites, and their combined effects on plants are not yet fully understood. To investigate the mechanisms underlying the co-exposure of Cd and PAHs and identify key biomarkers for their co-effects, an integrated analysis of metabolomics, transcriptomics, and proteomics was conducted on ryegrass leaves cultivated in soil. In nontarget metabolomics analysis, nine differentially expressed metabolites that were specifically induced by the compound exposure were identified. When combined with the analysis of differentially expressed genes and proteins, it was determined that the major pathways involved in the response to the co-stress of Cd and PAHs were linoleic acid metabolism and phenylpropanoid biosynthesis. The upregulation of 12,13-dihydroxy-9Z-octadecenoic acid and the downregulation of sinapyl alcohol were identified as typical biomarkers, respectively. Compared to scenarios of single exposures, the compound exposure to Cd and PAHs disrupted the oxidation of linoleic acid, leading to alterations in the profiles of linoleate metabolites. Additionally, it intensified hydroxylation, carboxylation, and methylation processes, and interfered with reactions involving coenzyme A, thus inhibiting lignin production. As a result, oxidative stress was elevated, and the cell wall defense system in ryegrass was weakened. The findings of this study highlight the ecological risks associated with unique biological responses in plants co-exposed to Cd and PAHs in polluted soils.
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Lolium , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Cádmio/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Lolium/metabolismo , Ácido Linoleico/metabolismo , Ácido Linoleico/farmacologia , Proteômica , Transcriptoma , Biodegradação Ambiental , Solo , Metabolômica , Biomarcadores/metabolismo , Poluentes do Solo/análiseRESUMO
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Neoplasias Hepáticas/metabolismo , Progressão da Doença , Fibrose , Receptores Toll-LikeRESUMO
Stabilization technology is widely used in the remediation of heavy metal-contaminated farmland soil. However, the evaluation method for the remediation effect is not satisfactory. To scientifically evaluate the remediation effect, this study constructed a comprehensive evaluation system by bibliometric analysis and an analytic hierarchy process (AHP). Ultimately, 16 indicators were selected from three aspects of the soil, crops, and amendment. The 16 indicators are divided into three groups, namely indicators I that can be evaluated according to the national standards of China, indicators II that can be evaluated according to the classification management of farmland and Indicators III that are the dynamic change indicators without an evaluation criterion. Comprehensive scores for 16 indicators were calculated using three response models, respectively. According to the difference between the scores before and after the remediation, the remediation effect is divided into five levels, which are excellent, good, qualified, poor, and very poor. This study provides a theoretical basis and insightful information for a farmland pollution remediation and a sustainable utilization.
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Recuperação e Remediação Ambiental , Metais Pesados , Processo de Hierarquia Analítica , Poluição Ambiental , SoloRESUMO
Studying the pollution status, spatial distribution characteristics, and sources of heavy metals in farmland soil in Anxin County will provide a method basis for the next step of soil remediation. This study investigates the contents of Zn, Cu, Pb, Cd, and Ni in wheat grains and soil samples. Moreover, different methods are used to evaluate soil heavy metal pollution. The results show that the soil in the study area is weakly alkaline. Cu, Zn, and Ni contents in the ground are lower than the risk screening values for soil contamination of agricultural land. In comparison, Cd and Pb contents are higher than the screening value of soil pollution risk of agricultural land, and the proportion of points lower than the control value of soil pollution risk of agricultural land are 64.58% and 16.67%, respectively. The farmland with high Cd and Pb content is mainly distributed near roads and factories and concentrated primarily on 0-20 cm topsoil. The Cd content in wheat grains meets the standard, but 4.17% of the samples are close to 0.1 mg kg-1 (more than 0.09 mg kg-1). The Pb content of 50% of the wheat grain samples exceeds the lead limit in the standard. The evaluation results of the single factor pollution index and geoaccumulation index show that the pollution degree of heavy metals in the soil is Cd > Pb > Cu > Zn > Ni. The potential ecological risk index in the study area is 288.83, and the soil heavy metal pollution is at a moderate-considerable ecological risk level. The average value of Cd's single-factor environmental risk index is 233.51, which belongs to the high environmental risk and is the main influencing factor. Cd and Pb in soil are significantly disturbed by the production activities of heavy metal processing enterprises around the farmland. It is speculated that there are two primary sources of soil heavy metal pollution in the study area. Cd, Pb, Zn, and Cu are mainly industrial and mobile sources, and Ni is primarily agricultural and natural sources.
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Metais Pesados , Poluentes do Solo , Cádmio/análise , China , Monitoramento Ambiental , Fazendas , Chumbo/análise , Metalurgia , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análiseRESUMO
Highly oxygenated organic molecules (HOM) formed by the autoxidation of α-pinene initiated by OH radicals play an important role in new particle formation. It is believed that the accretion products, ROOR´, formed by the self- and cross-reaction of peroxy radicals (RO2â¯+â¯R'O2 reactions), have extremely low volatility and are more likely to participate in nucleation. However, the mechanism of ROOR´ formation has not been fully demonstrated by experiment or theoretical calculation. Herein, we propose a novel mechanism of RO2 reacting with α-pinene (RO2â¯+â¯α-pinene reactions) that have much lower potential barriers and larger rate constants than the reaction of RO2 with R'O2, which explains the ROOR´ formation found in the mass spectrometry experiments. The ROOR´ resulting from the reaction of RO2 with α-pinene can produce HOM dimers and trimers with a higher oxygen-tocarbon (O/C) ratio through a autoxidation chain. We also demonstrated that the presence of NOx and HO2 radical will reduce the RO2 concentration, but cannot completely inhibit the formation of HOM monomers and ROOR´. Even if one or both of RO2 radicals are acyl peroxy radicals (RC(O)O2), the potential barriers of the reactions between RC(O)O2 and α-pinene (RC(O)O2â¯+â¯α-pinene reactions) are lower than that of RO2 reacting with RC(O)O2 (RO2â¯+â¯RC(O)O2 reactions) or RC(O)O2 self-reactions (RC(O)O2â¯+â¯RC(O)O2 reactions). The current work revealed, for the first time, a mechanism of RO2/RC(O)O2 reacting with α-pinene in the atmosphere, which provides new insight into the atmospheric chemistry of accretion products as SOA precursors.
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Atmosfera , Oxigênio , Atmosfera/química , Monoterpenos Bicíclicos , Carbono , Oxigênio/químicaRESUMO
[This corrects the article DOI: 10.3389/fonc.2022.947284.].