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The biaxial compression experiments of rock-like materials with two flaws are carried out under different flaw inclination angle, rock bridge ligament angle, lateral stress. The experimental studies show that crack propagation modes of rock-like material are as follows: wing crack through mode (Y mode), shear crack through mode (J mode), mixed crack through mode (wing shear JY mode), longitudinal extension of crack and transverse shear splitting. prefabricated fractured rock specimens have experienced the closing stage of prefabricated fractures, the elastic deformation stage, the generation and expansion of cracks (or plastic strengthening), and the residual loading stage. The peak strength of the specimen is increases with the increase of flaw inclination angle and lateral stress. With the increase of the rock bridge ligament angle, the failure of the rock bridge region changes from the shear crack failure to composite failure of shear crack and the wing type tensile crack failure, and then to the wing crack failure. With the increase of the lateral pressure, the failure of the specimen changes from the wing type tensile crack failure to the wing type and shear crack failure, and then to shear crack failure. The flaw inclination angle mainly changes the form of crack growth but does not effect on the failure modes. The counting number of acoustic emission events at the center of the sample is relative large, indicating that the cacks appear in the part of the rock bridge firstly. With the increasing of loads, the cracks of the rock bridge expanding constantly and connecting finally. The changes of acoustic emission event counts is consistent with the macroscopic damage form obtained from the experiments.
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Embodied emissions from the production of building materials account for 17% of China's carbon dioxide (CO2) emissions and are important to focus on as China aims to achieve its carbon neutrality goals. However, there is a lack of systematic assessments on embodied emissions reduction potential of building materials that consider both the heterogeneous industrial characteristics as well as the Chinese buildings sector context. Here, we developed an integrated model that combines future demand of building materials in China with the strategies to reduce CO2 emissions associated with their production, using, and recycling. We found that measures to improve material efficiency in the value-chain has the largest CO2 mitigation potential before 2030 in both Low Carbon and Carbon Neutrality Scenarios, and continues to be significant through 2060. Policies to accelerate material efficiency practices, such as incorporating embodied emissions in building codes and conducting robust research, development, and demonstration (RD&D) in carbon removal are critical.
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BACKGROUND: Heavy metals entering the human body could cause damage to a variety of organs. However, the combined harmful effects of exposure to various metals on liver function are not well understood. The purpose of the study was to investigate the independent and joint relationships between heavy metal exposure and liver function in adults. METHODS: The study involved 3589 adults from the National Health and Nutrition Examination Survey. Concentrations of urinary metals, including arsenic (As), cadmium (Cd), lead (Pb), antimony (Sb), barium (Ba), thallium (Tl), tungsten (W), uranium (U), were determined in urine using inductively coupled plasma mass spectrometry. Data for liver function biomarkers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transaminase (GGT), and alkaline phosphatase (ALP). Survey-weighted linear regression and quantile g-computation (qgcomp) were employed to evaluate the relationship of urinary metals with the markers of liver injury. RESULTS: Cd, U and Ba were found to have positive correlations with ALT, AST, GGT, and ALP in the survey-weighted linear regression analyses. According to the qgcomp analyses, the total metal mixture was positively correlated with ALT (percent change: 8.15; 95% CI: 3.84, 12.64), AST (percent change: 5.55; 95% CI: 2.39, 8.82), GGT (percent change: 14.30; 95% CI: 7.81, 21.18), and ALP (percent change: 5.59; 95% CI: 2.65, 8.62), and Cd, U, and Ba were the main contributors to the combined effects. Positive joint effects were observed between Cd and U on ALT, AST, GGT and ALP, and U and Ba had positive joint effects on ALT, AST and GGT. CONCLUSION: Exposures to Cd, U, and Ba were individually associated with multiple markers of liver injury. Mixed metal exposure might be adversely correlated with markers of liver function. The findings indicated the potential harmful effect of metal exposure on liver function.
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Cádmio , Metais Pesados , Adulto , Humanos , Inquéritos Nutricionais , gama-Glutamiltransferase , Fígado , Biomarcadores , Fosfatase AlcalinaRESUMO
Microcystin-LR (MC-LR) is an extremely poisonous cyanotoxin that poses a threat to ecosystems and human health. MC-LR has been reported as an enterotoxin. The objective of this study was to determine the effect and the mechanism of subchronic MC-LR toxicity on preexisting diet-induced colorectal damage. C57BL/6J mice were given either a regular diet or a high-fat diet (HFD) for 8 weeks. After 8 weeks of feeding, animals were supplied with vehicle or 120 µg/L MC-LR via drinking water for another 8 weeks, and their colorectal were stained with H&E to detect microstructural alterations. Compared with the CT group, the HFD and MC-LR + HFD-treatment group induced a significant weight gain in the mice. Histopathological findings showed that the HFD- and MC-LR + HFD-treatment groups caused epithelial barrier disruption and infiltration of inflammatory cells. The HFD- and MC-LR + HFD-treatment groups raised the levels of inflammation mediator factors and decreased the expression of tight junction-related factors compared to the CT group. The expression levels of p-Raf/Raf and p-ERK/ERK in the HFD- and MC-LR + HFD-treatment groups were significantly increased compared with the CT group. Additionally, treated with MC-LR + HFD, the colorectal injury was further aggravated compared with the HFD-treatment group. These findings suggest that by stimulating the Raf/ERK signaling pathway, MC-LR may cause colorectal inflammation and barrier disruption. This study suggests that MC-LR treatment may exacerbate the colorectal toxicity caused by an HFD. These findings offer unique insights into the consequences and harmful mechanisms of MC-LR and provide strategies for preventing and treating intestinal disorders.
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Neoplasias Colorretais , Ecossistema , Humanos , Animais , Camundongos , Camundongos Obesos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Microcistinas/toxicidade , Inflamação/induzido quimicamenteRESUMO
Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose-response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD.
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Arsênio , Insuficiência Renal Crônica , Humanos , Cádmio , Estudos de Casos e Controles , Microcistinas , Teorema de Bayes , Exposição Ambiental , Insuficiência Renal Crônica/epidemiologia , ChinaRESUMO
Obesity, a metabolic disease caused by excessive fat accumulation in the body, has attracted worldwide attention. Microcystin-LR (MC-LR) is a hepatotoxic cyanotoxin which has been reportedly to cause lipid metabolism disorder. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for eight weeks to build obese an animal model, and subsequently, the obese mice were fed MC-LR for another eight weeks, and we aimed to determine how MC-LR exposure affects the liver lipid metabolism in high-fat-diet-induced obese mice. The results show that MC-LR increased the obese mice serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating damaged liver function. The lipid parameters include serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and liver TG, which were all increased, whilst the high-density lipoprotein cholesterol (HDL-c) was decreased. Furthermore, after MC-LR treatment, histopathological observation revealed that the number of red lipid droplets increased, and that steatosis was more severe in the obese mice. In addition, the lipid synthesis-related genes were increased and the fatty acid ß-oxidation-related genes were decreased in the obese mice after MC-LR exposure. Meanwhile, the protein expression levels of phosphorylation phosphatidylinositol 3-kinase (p-PI3K), phosphorylation protein kinase B (p-AKT), phosphorylation mammalian target of rapamycin (p-mTOR), and sterol regulatory element binding protein 1c (SREBP1-c) were increased; similarly, the p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and SREBP1/ß-actin were significantly up-regulated in obese mice after being exposed to MC-LR, and the activated PI3K/AKT/mTOR/SREBP1 signaling pathway. In addition, MC-LR exposure reduced the activity of superoxide dismutase (SOD) and increased the level of malondialdehyde (MDA) in the obese mice's serum. In summary, the MC-LR could aggravate the HFD-induced obese mice liver lipid metabolism disorder by activating the PI3K/AKT/mTOR/SREBP1 signaling pathway to hepatocytes, increasing the SREBP1-c-regulated key enzymes for lipid synthesis, and blocking fatty acid ß-oxidation.
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Fígado Gorduroso , Transtornos do Metabolismo dos Lipídeos , Fígado , Toxinas Marinhas , Microcistinas , Animais , Camundongos , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Toxinas Marinhas/toxicidade , Microcistinas/toxicidadeRESUMO
Objective: To investigate the relationship between postoperative hypothalamo-hypophyseal injury (HHI) and postoperative water and sodium disturbances in patients with craniopharyngioma. Methods: The medical records, radiological data, and laboratory results of 178 patients (44 children and 134 adults) who underwent microsurgery for craniopharyngioma in a single center were reviewed. Postoperative HHI was assessed using magnetic resonance imaging. Structural defects of the hypothalamo-hypophyseal system (pituitary, pituitary stalk, floor and lateral wall of the third ventricle) were assessed in four standard T1-weighted images. The defect of each structure was assigned 1 score (0.5 for the unilateral injury of the third ventricle wall), and a HHI score was calculated. Results: The number of patients with HHI scores of 0-1, 2, 2.5-3, and >3 was 35, 49, 61, and 33, respectively. Diabetes insipidus (DI) worsened in 56 (31.5%) patients with preoperative DI, while 119 (66.9%) patients were diagnosed with new-onset DI. Hypernatremia and hyponatremia developed in 127 (71.3%) and 128 (71.9%) patients after surgery, respectively. Syndrome of inappropriate antidiuresis occurred in 97(54.5%) patients. During hospitalization, hypernatremia recurred in 33 (18.5%) patients and in 54 (35.7%) during follow-up, of which 18 (11.9%) were severe. DI persisted in 140 (78.7%) patients before discharge. No relationship was found between the HHI score and incidence of early DI, hyponatremia, syndrome of inappropriate diuretic hormone, or prolonged DI. Compared with patients with a score of 0-1, those with scores =2.5-3 (OR = 5.289, 95% CI:1.098-25.477, P = 0.038) and >3 (OR = 10.815, 95% CI:2.148-54.457, P = 0.004) had higher risk of developing recurrent hypernatremia. Patients with a score >3 had higher risk of developing severe hypernatremia during hospitalization (OR = 15.487, 95% CI:1.852-129.539, P = 0.011) and at follow-up (OR = 28.637, 95% CI:3.060-267.981, P = 0.003). Conclusions: The neuroimaging scoring scale is a simple tool to semi-quantify HHI after surgery. Recurrent and severe hypernatremia should be considered in patients with a high HHI score (>2.5). An HHI score >3 is a potential predictor of adipsic DI development. Preventive efforts should be implemented in the perioperative period to reduce the incidence of potentially catastrophic complications.
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Lesões Encefálicas Traumáticas , Craniofaringioma , Diabetes Insípido , Hipernatremia , Hiponatremia , Neoplasias Hipofisárias , Adulto , Lesões Encefálicas Traumáticas/complicações , Criança , Craniofaringioma/complicações , Craniofaringioma/cirurgia , Diabetes Insípido/complicações , Diuréticos , Hormônios , Humanos , Hipernatremia/epidemiologia , Hipernatremia/etiologia , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Sódio , ÁguaRESUMO
Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin (NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., N-terminal, loops 1-4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a (Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4, and the C-terminal primarily interacted with the S3-S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7. Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.
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Venenos de Aranha , Animais , Peptídeos/química , Canais de Sódio , Venenos de Aranha/química , Venenos de Aranha/genética , Venenos de Aranha/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêuticoRESUMO
Colloids have a significant influence on the migration of nuclides in claystone, which is an important geological barrier. The sorption of strontium on claystone in the presence of FeOOH colloids was investigated in samples from the Suhongtu site, a candidate high-level radioactive waste disposal site in China. The effects of colloid amount, solid content, and pH were investigated by batch tests, and the sorption reaction mechanism was analyzed by kinetic modeling and microscopic characterization techniques. The results indicate that the sorption of Sr by claystone increased with the solids content, and the claystone had a stronger Sr sorption capacity under alkaline conditions. The Sr sorption kinetics were best described by the pseudo-first-order and pseudo-second-order models, which revealed that the progress is affected by physical diffusion and chemical sorption. Furthermore, the microscopic characterization results demonstrate that cation exchange reactions and surface complex reactions are the main sorption mechanisms for Sr sorption on claystone. Ca and Mg plasmas in claystone minerals can have cation replacement reactions with Sr, and functional groups such as -OH and [CO3]2- can have complexation reactions with Sr to adsorb Sr on the surface of the claystone. Additionally, the presence of the FeOOH colloid inhibited the sorption effect of claystone slightly. The FeOOH colloid could occupy sorption sites on the claystone surface, which reduces the activity of the functional groups and inhibits the sorption of Sr on claystone.
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The bentonite colloid produced in the deep geological repository of high-level radioactive waste can directly affect the migration of radionuclide strontium when it acts on claystone. The adsorption characteristics of strontium were investigated on claystone with the presence or absence of bentonite colloids from the Suhongtu area of China. The effects of different influencing factors, such as pH and solid content, on the adsorption process were investigated by batch adsorption experiments, and spectroscopic techniques were used to characterize the samples before and after adsorption of strontium. The results show that the presence of bentonite colloids can promote the adsorption of strontium on claystone under alkaline conditions. and the general order kinetic model provided the best fit to the experimental data. Strontium is adsorbed on the surface of claystone and bentonite colloid by ion exchange and surface complexation. Most of the Sr2+ formed SrCO3 with CO32- after ion exchange with Ca2+ and Mg2+ in plagioclase and dolomite, and a small amount of Sr2+ was adsorbed by complexation with -OH, Al-O and Si-O. These results provide a scientific basis for predicting the migration of strontium in subsurface porous media and the siting of high-level radioactive waste repositories.
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Resíduos Radioativos , Adsorção , Bentonita/química , Coloides/química , Resíduos Radioativos/análise , Estrôncio/químicaRESUMO
Microcystin-LR (MC-LR), a potent hepatotoxin can cause liver damages. However, research on hepatic lipid metabolism caused by long-term exposure to environmental concentrations MC-LR is limited. In the current study, mice were exposed to various low concentrations of MC-LR (0, 1, 30, 60, 90, 120 µg/L in the drinking water) for 9 months. The general parameters, serum and liver lipids, liver tissue pathology, lipid metabolism-related genes and proteins of liver were investigated. The results show that chronic MC-LR exposure had increased the levels of triglyceride (TG) and total cholesterol (TC) in serum and liver. In addition, histological observation revealed that hepatic lobules were disordered with obvious inflammatory cell infiltration and lipid droplets. More importantly, the mRNA and proteins expression levels of lipid synthesis-related nuclear sterol regulatory element binding protein-1c (nSREBP-1c), SREBP-1c, cluster of differentiation 36 (CD36), acetyl-CoA-carboxylase1 (ACC1), stearoyl-CoA desaturase1 (SCD1) and fatty acid synthase (FASN) were increased in MC-LR treated groups, the expression levels of fatty acids ß-oxidation related genes peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) was decreased after exposure to 60-120 µg/L MC-LR. Furthermore, the inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were higher than that in the control group. All the findings indicated that mice were exposed to chronic low concentrations MC-LR caused liver inflammation and hepatic lipid metabolism disorder .
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Transtornos do Metabolismo dos Lipídeos , Metabolismo dos Lipídeos , Microcistinas , Animais , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/patologia , Fígado/metabolismo , Fígado/fisiopatologia , Toxinas Marinhas/toxicidade , Camundongos , Microcistinas/toxicidade , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Soil labile organic carbon (LOC) responds rapidly to environmental changes and plays an important role in carbon cycle. In this study, the seasonal fluctuations in LOC, the activities of carbon-cycle related enzymes, and the bacterial and fungal communities were analyzed for soils collected from two forests, namely Betula albosinensis (Ba) and Picea asperata Mast. (Pa), in the Qinling Mountains of China. Results revealed that the seasonal average contents of microbial biomass carbon (MBC), easily oxidized organic carbon (EOC), and dissolved organic carbon (DOC) of Pa forest soil were 13.5%, 30.0% and 15.7% less than those in Ba soil. The seasonal average enzyme activities of ß-1,4-glucosidase (ßG), and ß-1,4-xylosidase (ßX) of Ba forest soils were 30.0% and 32.3% higher than those of Pa soil while the enzyme activity of cellobiohydrolase (CBH) was 19.7% lower. Furthermore, the relative abundance of Acidobacteria was significantly higher in summer than in winter, whereas the relative abundance of Bacteroidetes was higher in winter. Regarding the fungal communities, the relative abundance of Basidiomycota was lowest in winter, whereas Ascomycota predominated in the same season. In addition, the soil LOC was significantly positively correlated with the CBH, ßG and ßX activities. Changes in LOC were significantly correlated with Acidobacteria, Bacteroidetes and Basidiomycota. We conclude that the seasonal fluctuations in forest soil LOC fractions relied on carbon cycle-associated enzymatic activities and microorganisms, which in turn were affected by climatic conditions.
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Colloids in groundwater or geological barriers generally play a key role in the migration of special nuclides. Adsorption characteristics of strontium were investigated on porous media in the presence of colloidal Fe(OH)3 from the Beishan Site, the only high-level radioactive waste disposal site candidate in China. The effects of colloid amounts, solid contents, and pH were determined and studied by batch texts. The results revealed that the presence of colloidal Fe(OH)3 in porous media contributed to promotion of the sorption effect, and the influencing factors had a significant impact on the adsorption process. The sorption ability increased with increasing colloid amount when the equilibrium time was approximately 10 h under an optimal solid-liquid ratio of 20 g L-1. The sorption effect in alkaline conditions was better than that under acidic conditions. The sorption kinetics indicated that the strong chemical interaction and/or surface complexation contributed primarily to strontium sorption. The sorption isotherms and model fitting revealed that the sorption of strontium onto porous media in the presence of colloidal Fe(OH)3 was a monolayer adsorption, and the presence of colloidal Fe(OH)3 is an important factor that greatly influences the removal of strontium from aqueous solutions. These findings provide useful information for the treatment of strontium in radioactive waste disposal sites.
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Resíduos Radioativos , Estrôncio , Instalações de Eliminação de Resíduos , Adsorção , China , Compostos Férricos/química , PorosidadeRESUMO
Bench-scale experiments were conducted to investigate the effect of hydraulic loadings and influent concentration on the migration and biotransformation behavior of three groundwater pollutants: ammonium (NH4 +), iron (Fe2+) and manganese (Mn2+). Columns packed with aquifer media collected from a river bank filtration (RBF) site in Harbin City, NE China were introduced synthetic groundwater (SGW) or real groundwater (RGW) were at two different constant flow rates and initial contaminant concentrations to determine the impact of system conditions on the fate of the target pollutants biotransformation. The results showed that the biotransformation rate of Fe2+ Mn2+, and NH4 + decreased by 8%, 39% and 15% under high flow rate (50 L d-1) compared to low flow rate (25 L d-1), which was consistent with the residence-time effect. While the biotransformation rate of Fe2+ Mn2+, and NH4 + decreased by 7%, 14% and 9% under high influent concentration compared to original groundwater. The 16S rRNA analysis of the aquifer media at different depths after experiments completion demonstrated that the relative abundance of major functional microbes iron oxidizing bacteria (IOB) and manganese oxidizing bacteria (MnOB) under higher flow rate and higher influent concentration decreased 13%, 14% and 25%, 24%, respectively, whereas the ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) exhibited minimal change, compared to the lower flow rate. Above all results indicated that both high flow rate and high concentration inhibit the biotransformation of NH4 +, Fe2+ and Mn2+. The biotransformation of Fe2+ and Mn2+ occurs primarily in the 0-40 cm and 20-60 cm depth intervals, respectively, whereas the NH4 + biotransformation appears to occur relatively uniformly throughout the whole 110cm column. The biotransformation kinetics of NH4 + in RGW and SGW, Mn2+ in RGW at different depths accords with the first order kinetics model, while Fe2+ in RGW and SGW, Mn2+ in SGW presented more complicated biotransformation process. The results should improve understanding of the transport and fate of common groundwater pollutants in riverbank filtration and other groundwater recharge environments.
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PURPOSE: Glioblastoma is the most malignant glioma tumors with inevitable relapse and resistance to chemotherapy; however, the mechanisms driving chemoresistance remain to be fully elucidated. This study is to explore the molecular and cellular mechanisms involving in the chemoresistance of glioblastoma. METHODS: The expression of musashi (MSI) RNA-binding protein in the tumor tissues and cells of glioblastoma was measured. The effects of MSI2 in epithelial-to-mesenchymal transition (EMT), resistance to temozolomide (TMZ), tumor cell invasion, migration, and proliferation and associated signaling were evaluated. RESULTS: High MSI2 expression was observed in the glioblastoma tissues. Silencing or overexpression of MSI2 significantly affected tumor cells invasion, migration, and proliferation. Silencing of MSI2 expression significantly inhibited O6-methylguanine-DNA methyltransferase (MGMT) expression and tumor growth, and reversed resistance to TMZ in xenograft tumor models. MSI2 expression regulated EMT through activating the transcription factors Snail and the TGFß R1/SMAD3 signaling. CONCLUSIONS: Our study demonstrated a positive feedback loop of MSI2-TGFß/SMAD3 signaling which activates the EMT and MGMT which may contribute to chemoresistance in glioblastoma. This study also highlights that MSI2 could be a new target for the therapy of glioblastoma.
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Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/genética , Proteínas de Ligação a RNA/genética , Proteína Smad3/genética , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Camundongos , Transdução de SinaisRESUMO
BACKGROUND: Systemic inflammation is known as a risk factor of cognitive decline. OBJECTIVE: To investigate the effects of propolis on cognitive decline and systemic inflammation in elderly people living at high altitude. METHODS: Sixty participants (average 72.8 years) living at altitude (2,260 meters) were randomized to receive propolis (0.83âg, nâ=â30) or placebo (nâ=â30) for 24 months. Cognitive outcomes were assessed using MMSE and serum cytokine levels were measured for 24 months in a double-blind study. RESULTS: MMSE scores were 26.17 at baseline and 23.87 at 24 months in placebo group. Compared to placebo group, improvements of MMSE scores were significant in propolis-treated subjects (pâ=â0.007) with a response emerging over time (time points×group interaction, pâ=â0.016). In addition, the serum IL-1ß and IL-6 levels were significantly different across treatments (pâ<â0.0001) showing upward and downward trends in placebo- and propolis-treated subjects, respectively (pâ<â0.0001). Serum levels of TNF-α were not significantly different across treatment (pâ=â0.0528) but with a response emerging over time (time points×group interaction, pâ=â0.016). In contrast, serum levels of TGFß1 were significantly different across treatments (pâ<â0.0001) showing downward and upward trends in placebo- and propolis-treated subjects, respectively. Serum levels of IL-10 were significant for the effect of groups (pâ=â0.0411). Furthermore, MMSE scores correlated with the decrease in IL-1ß and the increase in TGFß1 in serum. CONCLUSION: Elderly people living at high altitude developed to MCI in 24 months with exacerbation of systemic inflammation. Ingestion of propolis (>12 months) protected against cognitive decline after systemic inflammation was reduced.
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Altitude , Anti-Inflamatórios não Esteroides/uso terapêutico , Apiterapia , Disfunção Cognitiva/prevenção & controle , Inflamação/tratamento farmacológico , Própole/uso terapêutico , Idoso , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/psicologia , Masculino , Testes de Estado Mental e Demência , Resultado do TratamentoRESUMO
Microbial communities in subsurface soil are specialized for their environment, which is distinct from that of the surface communities. However, little is known about the microbial communities (bacteria and fungi) that exist in the deeper soil horizons. Vertical changes in microbial alpha-diversity (Chao1 and Shannon indices) and community composition were investigated at four soil depths (0-10, 10-20, 20-40, and 40-60 cm) in a natural secondary forest of Betula albosinensis by high-throughput sequencing of the 16S and internal transcribed spacer rDNA regions. The numbers of operational taxonomic units (OTUs), and the Chao1 and Shannon indices decreased in the deeper soil layers. Each soil layer contained both mutual and specific OTUs. In the 40-60 cm soil layer, 175 and 235 specific bacterial and fungal OTUs were identified, respectively. Acidobacteria was the most dominant bacterial group in all four soil layers, but reached its maximum at 40-60 cm (62.88%). In particular, the 40-60 cm soil layer typically showed the highest abundance of the fungal genus Inocybe (47.46%). The Chao1 and Shannon indices were significantly correlated with the soil organic carbon content. Redundancy analysis indicated that the bacterial communities were closely correlated with soil organic carbon content (P = 0.001). Collectively, these results indicate that soil nutrients alter the microbial diversity and relative abundance and affect the microbial composition.
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Bactérias/isolamento & purificação , Betula , Florestas , Fungos/isolamento & purificação , Consórcios Microbianos , Microbiologia do Solo , Acidobacteria/classificação , Acidobacteria/genética , Acidobacteria/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Biodiversidade , Fungos/classificação , Fungos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Consórcios Microbianos/genética , Solo/químicaRESUMO
The single and dual cooperated proton transfer dynamic process in the excited state of 1,5-dihydroxyanthraquinone (1,5-DHAQ) was theoretically investigated, taking solvent effects (ethanol) into account. The absorption and fluorescence spectra were simulated, and dual fluorescence exhibited, which is consistent with previous experiments. Analysis of the calculated IR and Raman vibration spectra reveals that the intramolecular hydrogen bonding interactions (O20-H21···O24 and O22-H23···O25) are strengthened following the excited proton transfer process. Finally, by constructing the potential energy surfaces of the ground state, first excited singlet state, and triplet state, the mechanism of the intramolecular proton transfer of 1,5-DHAQ can be revealed.
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In this study, vertical changes in bacterial α-diversity and community composition were investigated at four soil depths(0-10, 10-20, 20-40 and 40-60 cm) in Betula albosinensis Burkill forest of Qinling Mountains by sequencing of the 16S rDNA regions using Illumina MiSeq high-throughput technology. The results showed that the decreases of OTUs, Chao1 and Shannon were numerical but not significant, and the highest values of 1688, 2314 and 8.66 were obtained in 0-10 cm, respectively. At the phylum level, Acidobacteria and Proteobacteria were the most dominant bacteria in four soil layers. At the genus level, Gp4, Gp6 and Gp16 were the most dominant bacteria. The relative abundance of Acidobacteria in 40-60 cm soil depth(62.88%) was higher than those in other soil depths. Proteobacteria in 0-10 cm(23.62%) was more abundant than that in 40-60 cm. The relative abundance of Acidobacteria was significantly correlated with the total N, soil organic carbon, C/N, and soil dissolved organic carbon. Soil water content, soil organic matter and soil dissolved organic carbon were the key factors affecting soil Proteobacteria. RDA sequencing results showed that soil dissolved organic carbon was the key factor contributing to the bacteria community abundance. The results demonstrated that there are plenty of bacterial distribution in all four soil layers, which provides a fundamental basis for vertical soil bacterial community diversity, and possesses very important research value in biogeochemical cycling.