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The RNA N6-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood. In this study, we demonstrated that METTL3 was overexpressed and associated with poor survival in most PCa patients. METTL3 inhibitor STM2457 reduced m6A levels of PCa cells, thus inhibiting their proliferation, colony formation, migration, invasion, and stemness in vitro. Furthermore, STM2457 suppressed PCa progression in both the CDX and PDX models in vivo. MeRIP-seq analysis coupled with biological validation revealed that STM2457 influenced multiple biological processes in PCa cells, mainly through the IGFBP3/AKT pathway. We also proved that STM2457 induced DNA damage and showed synergistic anti-PCa effects with the PARP inhibitor olaparib both in vitro and in vivo. All in all, this work provides a novel therapeutic strategy for targeting RNA m6A modifications for the treatment of PCa and provides a meaningful reference for further clinical trials.
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Proliferação de Células , Progressão da Doença , Sinergismo Farmacológico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Metiltransferases , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Metiltransferases/metabolismo , Metiltransferases/antagonistas & inibidores , Animais , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Adenosina/análogos & derivados , Adenosina/farmacologiaRESUMO
Traditional chemotherapy drugs for cervical cancer often cause significant toxic side effects and drug resistance problems, highlighting the urgent need for more innovative and effective treatment strategies. Magnesium alloy is known to be degradable and biocompatible. The release of degradation products Mg2+, OH-, and H2 from magnesium alloy can alter the tumor microenvironment, providing potential anti-tumor properties. We explored the innovative use of magnesium alloy biomaterials in the treatment of cervical cancer, investigating how various concentrations of Mg2+ on the proliferation and cell death of cervical cancer cells. The results revealed that varying concentrations of Mg2+ significantly inhibited cervical cancer by arresting the cell cycle in the G0/G1 phase and inducing apoptosis in SiHa cells, effectively reducing tumor cell proliferation. In vivo experiments demonstrated that 20 mM Mg2+ group had the smallest tumor volume, exhibiting a potent inhibitory effect on the biological characteristics of cervical cancer. This enhances the therapeutic potential of this biomaterial as a local anti-tumor therapy and lays a theoretical foundation for the potential application of magnesium in the treatment of cervical cancer.
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Apoptose , Materiais Biocompatíveis , Proliferação de Células , Magnésio , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Magnésio/farmacologia , Magnésio/química , Humanos , Proliferação de Células/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Ligas/farmacologia , Ligas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Ciclo Celular/efeitos dos fármacosRESUMO
Purpose: Bladder cancer (BLCA) is a highly heterogeneous tumor. We aim to construct a classifier from the perspective of N6-methyladenosine methylation (m6A) to identify patients with different prognostic risks and treatment responsiveness for precision therapy. Methods: Data on gene expression profile, mutation, and clinical characteristics were mainly obtained from the TCGA-BLCA cohort. Unsupervised clustering was performed to construct m6A subtypes. The tumor microenvironment (TME) landscapes were explored by using ssGSEA, ESTIMATE, and MCPcounter algorithms. K-M survival curves and Cox regression analysis were used to demonstrate the significance of m6A subtypes in predicting prognosis. pRRophetic, oncoPredict, and TIDE algorithms were used to evaluate responsiveness to antitumor therapy. A classifier of m6a subtypes was finally developed based on random forest and artificial neural network (ANN). Results: The two m6A subtypes have significantly different m6A-related gene expression profiles and mutational landscapes. TME analysis showed a higher level of stromal and Inhibitory immune components in subtype B compared with subtype A. The m6A subtype is a clinically independent prognostic predictor of BLCA, subtype B has a poorer prognosis. Drug sensitivity analysis showed that subtype B has lower IC50 values and AUC values for cisplatin and docetaxel. Efficacy assessment showed significantly poorer radiotherapy efficacy and lower immunotherapy responsiveness in subtype B. We finally constructed an ANN classifier to accurately classify BLCA patients into two m6A subtypes. Conclusion: Our study developed a classifier for identifying subtypes with different m6A characteristics, and BLCA patients with different m6A subtypes have significantly different prognosis and responsiveness to antitumor therapy.
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The effects of cast iron pipe corrosion on water quality risk and microbial ecology in drinking water distribution systems (DWDSs) were investigated. It was found that trihalomethane (THMs) concentration and antibiotic resistance genes (ARGs) increased sharply in the old DWDSs. Under the same residual chlorine concentration conditions, the adenosine triphosphate concentration in the effluent of old DWDSs (Eff-old) was significantly higher than that in the effluent of new DWDSs. Moreover, stronger bioflocculation ability and weaker hydrophobicity coexisted in the extracellular polymeric substances of Eff-old, meanwhile, iron particles could be well inserted into the structure of the biofilms to enhance the mechanical strength and stability of the biofilms, hence enhancing the formation of THMs. Old DWDSs significantly influenced the microbial community of bulk water and triggered stronger microbial antioxidant systems response, resulting in higher ARGs abundance. Corroded cast iron pipes induced a unique interaction system of biofilms, chlorine, and corrosion products. Therefore, as the age of cast iron pipes increases, the fluctuation of water quality and microbial ecology should be paid more attention to maintain the safety of tap water.
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Biofilmes , Ferro , Qualidade da Água , Abastecimento de Água , Corrosão , Microbiologia da Água , Água Potável/microbiologia , Água Potável/química , Resistência Microbiana a Medicamentos/genética , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Trialometanos/análiseRESUMO
Magnesium-based composites are a focal point in biomaterials research. However, the rapid degradation rate of magnesium alloys does not align with the healing time of bone tissue. Additionally, the host reaction caused by magnesium implantation hampers its full osteogenic potential. To maintain an appropriate microenvironment, it is important to enhance both corrosion resistance and osteogenic activity of the magnesium matrix. In this study, a composite scaffold composed of mineralized collagen and magnesium alloy was utilized to investigate the regulatory effect of mineralized collagen on mouse macrophages and evaluate its impact on mouse bone marrow mesenchymal stem cells in terms of osteogenesis, immune response, and macrophage-induced osteogenic differentiation. This experiment examined the biocompatibility of mouse bone marrow mesenchymal stem cells and macrophage-induced osteogenic differentiation in vitro, and examined the expression levels of relevant pathways proteins. Magnesium calcium alloys/mineralized collagen exhibited extensive spreading, facilitated by broad and abundant pseudopodia that firmly adhered them to the material surface and promoted growth and pseudopodia formation. The findings revealed that magnesium calcium alloy/mineralized collagen scaffold materials induced osteogenic differentiation mainly through M2 polarization of macrophages. This effect was mainly mediated by promoting the integrin α2ß1-FAK-ERK1/2 signaling pathways and inhibiting the RANK signaling pathways.
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Background: Magnesium (Mg) is an essential element and participates in many metabolic pathways. Many studies have found a certain negative correlation between magnesium and blood glucose parameters, but the dose-response relationship between them is still a relatively narrow research field. We aim to explore the dose-response relationship between plasma and dietary Mg and type 2 diabetes (T2DM) among childbearing women in a nationally representative sample. And we will also initially explore the threshold of dietary and plasma magnesium in the prevention of T2DM and their consistency. Methods: A total of 2912 18-44 year-old childbearing women were recruited from the China Adult Chronic Disease and Nutrition Surveillance (2015). Multivariate logistic regression was used to explore the dose-response relationship between plasma and dietary Mg and glucose parameters. The threshold effect between Mg and T2DM was explored by a restricted cubic spline regression. Results: It was found that when plasma Mg was increased by 0.041 mmol/L, the risk of T2DM, impaired fasting glucose (IFG), and HbA1c-hyperglycemia was reduced by 18%, 19%, and 18%, respectively. The possible threshold value for plasma Mg to prevent the risk of T2DM was 0.87 mmol/L. Through the quality control of the sample dietary survey data, 2469 cases were finally included for dietary analysis. And the possible threshold value for dietary Mg to prevent the risk of T2DM was 408 mg/d. Taking the recommended dietary Mg intake of 330 mg/d as the reference group, when the Mg intake reached 408 mg/d, the risk of T2DM was significantly reduced. And the average plasma Mg level of the people whose dietary intake reached 408 mg/d was 0.87 mmol/L. Conclusions: These results indicate that dietary Mg and plasma Mg have good consistency on the threshold effect of glucose parameters in women of childbearing age.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Magnésio , China/epidemiologia , Doença Crônica , GlucoseRESUMO
This study aims to investigate the impact of a tooth-brushing guidance system on the enchancement of the dental plaque removal in preschool children. In this study, we selected a group of 124 healthy children in which their aged were between 3 and 5 years old following by treatment at the Pediatric Dentistry Center at Jinzhou Stomatological Hospital (JinZhou, Liaoning Province, China). We then followed up to check and identify the Turesky modification of the Quigley-Hein plaque index (TMQHPI). Study group was randomly assigned to an experimental group in which they received constantly guidance on intelligent tooth-brushing and a control group which was used by manual brushing techniques. The total numbers in each group were 62 participants that were gone under the clinical investigation for seven days. The plaque index of both groups were assessed by using a plaque display instrument and a periodontal probe for up day 28. It was shown that the experimental group had a lower average TMQHPI value (0.98 ± 0.15) in comparison with control group (1.41 ± 0.17), and this difference was statistically significant (p < 0.05). The experimental group had a significantly lower TMQHPI value (0.89 ± 0.13) on the tongue/palatal side of the anterior teeth area in comparison with control group (1.41 ± 0.17) (p < 0.05). We observed that experimental group showed significantly lower TMQHPI value (1.16 ± 0.12) on the tongue/palatal side of the posterior dental region in comparison with control group (1.70 ± 0.13) (p < 0.05). It was confirmed a significant difference in the average plaque clearance rate between the experimental and control groups (p < 0.05). Our study clearly indicates that a developed method of toothbrush guide effectively improved the removal rate of plaque compared with manual tooth-brush, specifically in hard-to-reach areas like the tongue and palate.
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Placa Dentária , Pré-Escolar , Humanos , Estudos Cross-Over , Placa Dentária/prevenção & controle , Índice de Placa Dentária , Desenho de Equipamento , Método Simples-Cego , Escovação DentáriaRESUMO
Purpose: Magnesium (Mg) is an essential nutrient for the maintenance of vital physiological functions. Magnesium deficiency is associated with diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS); however, conclusions have been inconsistent, and there is a particular lack of evidence regarding this association in Chinese population older than 45 years. This study aimed to assess the association between plasma magnesium and the risk of MetS and its components, the dose-response relationship, and the threshold effect relationship in a Chinese population involving older than 45 years. Methods: A total of 2,101 individuals were randomly selected from the China Nutrition and Health Surveillance (CNHS) (2015-2017) by considering monitoring points. We used the joint statement of the International Diabetes Federation (IDF) in 2009 to define participants with MetS. The plasma magnesium was tested by inductively coupled plasma mass spectrometry (ICP-MS). The logistic regression and restricted cubic spline (RCS) models were used to analyze the association and dose-response relationship between plasma Mg and MetS and its components. Results: Compared with the lowest quintile (Q1) for plasma Mg, the odds ratios (ORs) and 95% confidence intervals (95% CI) for MetS, impaired fasting glucose (IFG), hypertension, and triglyceride (TG) elevation at the highest quintile (Q5) were 0.419 (0.301, 0.583), 0.303 (0.221, 0.415), 0.446 (0.322, 0.618), and 0.526 (0.384, 0.720), respectively, with all p < 0.05. However, in the components of decreased high-density lipoprotein cholesterol (HDL-C) and central obesity, no trend toward lowering with higher plasma magnesium was observed (p = 0.717, p = 0.865). These associations were not altered by further adjustment for potential confounding variables, including age, gender, education, nationality, area, residence, body mass index (BMI), and heart rate. The RCS analysis showed that, when plasma magnesium was lower than 0.85 mmol/L, the curve was leveled off, and then, the curve showed a decreasing trend with the increase in plasma magnesium. Conclusion: Therefore, plasma Mg was negatively associated with MetS and its components (including IFG, hypertension, and elevated TG) in people older than 45 years. In addition, plasma Mg greater than or equal to 0.85 mmol/L, which is higher than the commonly used threshold of 0.75 mmol/L, may be protective against MetS and its components (including elevated FPG, elevated blood pressure, and elevated TG). More prospective studies, such as randomized controlled trials, are necessary to confirm the effective impact of Mg on MetS and its components. Plasma Mg levels in the MetS population older than 45 years require attention.
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OBJECTIVE: To explore the relationship between serum 25-hydroxyvitamin D(25(OH)D) and serum parathyroid hormone(PTH) level in Chinese people aged 50 years and above, and to probe the optimum threshold for vitamin D sufficiency preliminarily, and apply this threshold to predict the risk of metabolic syndrome(Mets) in this population. METHODS: A total of 750 serum samples were selected from the biological samples' bank of Chinese Chronic Diseases and Nutritional Survey(CCDNS, 2015-2017) by stratified sampling, basic information(including age, gender, season, etc. ) were collected from questionnaire and physical measurement of the subjects were conducted unified. Serum 25(OH)D concentration was determined by high performance liquid chromatography tandem mass spectrometer, and PTH and interleukin-6(IL-6) were detected by electrochemiluminescence method. Phosphorus, albumin(Alb), creatinine(Cr) in blood were detected by automatic biochemical analyzer. Factors affecting the concentration of 25(OH)D and PTH were found by multiple linear regression and adjusted by generalized additive model separately, threshold was predicted by locally weighted regression and smoothing scatterplot, abbreviated as LOESS, and the exact threshold of 25(OH)D was found when PTH reached the plateau by nonlinear least squares estimation and segmented regression. Relationship between 25(OH)D and Mets was analyzed by multivariate logistic regression using the different cut-off points in Chinese elderly people. RESULTS: Reference threshold for vitamin D deficiency in Chinese elderly people can be preliminarily discovered as serum total 25(OH)D was 19.62 ng/mL, and 28.44 ng/mL can be used as reference threshold for sufficient vitamin D. Sufficient 25(OH)D(≥28.44 ng/mL) could reduce the risk of Mets significantly(OR=0.617(0.439-0.869)) after adjusting for confounding factors such as sex, age, region, season, ect. A plateau in PTH was observed at a 25(OH)D concentration of 20.03-28.43 ng/mL for male whereas 13.12-26.33 ng/mL for female by gender stratification analysis, but no cut-off point was obtained statistically. CONCLUSION: Reference threshold for vitamin D sufficiency in Chinese elderly people was preliminarily observed in the range of 19.62-28.44 ng/mL when PTH was maximally inhibited, and the threshold may vary with gender. Applying the threshold we also found that more sufficient levels of vitamin D were protective against Mets in this population.
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Hormônio Paratireóideo , Vitamina D , Idoso , Humanos , Masculino , Feminino , Calcifediol , Vitaminas , China/epidemiologiaRESUMO
Recently, it has been reported that chlorine dioxide (ClO2) and (bi)sulfite/ClO2 showed excellent performance in micropollutant removal from water; however, the degradation mechanisms and application boundaries of the two system have not been identified. In this study, bisphenol A (BPA) was chosen as the target contaminant to give multiple comparisons of ClO2 and S(IV)/ClO2 process regarding the degradation performance of contaminant, generation of reactive species, transformation of products and toxicity variation. Both ClO2 and S(IV)/ClO2 can degrade BPA within 3 min. The BPA degradation mechanism was mainly based on direct oxidation in ClO2 process while it was attributed to radicals (especially SO4·-) generation in S(IV)/ClO2 process. Meanwhile, the effect of pH and coexisting substances (Cl-, Br-, HCO3- and HA) were evaluated. It was found that ClO2 preferred the neutral and alkaline condition and S(IV)/ClO2 preferred the acidic condition for BPA degradation. An unexpected speed-up of BPA degradation was observed in ClO2 process in the presence of Br-, HCO3- and HA. In addition, the intermediate products in BPA degradation were identified. Three exclusive products were found in ClO2 process, in which p-benzoquinone was considered to be the reason of the acute toxicity increase in ClO2 process.
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Compostos Clorados , Poluentes Químicos da Água , Purificação da Água , Óxidos/toxicidade , Óxidos/química , Compostos Clorados/toxicidade , Compostos Clorados/química , Fenóis/toxicidade , Oxirredução , Cloro/química , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análiseRESUMO
The slow reduction of Cu(II) into Cu(I) through peracetic acid (PAA) heavily limited the widespread application of Cu(II)/PAA system. Herein, hydroxylamine (HA) was proposed to boost the oxidative capacity of Cu(II)/PAA system by facilitating the redox cycle of Cu(I)/Cu(II). HA/Cu(II)/PAA system was quite rapid in the removal of diclofenac within a broad pH range of 4.5-9.5, with a 10-fold increase in the removal rate of diclofenac compared with the Cu(II)/PAA system at an optimal initial pH of 8.5. Results of UV-Vis spectra, electron paramagnetic resonance, and alcohol quenching experiments demonstrated that CH3C(O)Oâ¢, CH3C(O)OOâ¢, Cu(III), and â¢OH were involved in HA/Cu(II)/PAA system, while CH3C(O)OO⢠was verified as the predominant reactive species of diclofenac elimination. Different from previously reported Cu-catalyzed PAA processes, CH3C(O)OO⢠mainly generated from the reaction of PAA with Cu(III) rather than CH3C(O)O⢠and â¢OH. Four possible elimination pathways for diclofenac were proposed, and the acute toxicity of treated diclofenac solution with HA/Cu(II)/PAA system significantly decreased. Moreover, HA/Cu(II)/PAA system possessed a strong anti-interference ability towards the commonly existent water matrix. This research proposed an effective strategy to boost the oxidative capacity of Cu(II)/PAA system and might promote its potential application, especially in copper-contained wastewater.
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Oxidation treatment of algae-laden water may cause cells rupture and emission of intracellular organics, thus restricting its further popularization. As a moderate oxidant, calcium sulfite could be slowly released in the liquid phase, thus exhibiting a potential to maintain the cells integrity. To this end, calcium sulfite oxidation activated by ferrous iron was proposed integrated with ultrafiltration (UF) for removal of Microcystis aeruginosa, Chlorella vulgaris and Scenedesmus quadricauda. The organic pollutants were significantly eliminated, and the repulsion between algal cells was obviously weakened. Through fluorescent components extraction and molecular weights distribution analyses, the degradation of fluorescent substances and the generation of micromolecular organics were verified. Moreover, the algal cells were dramatically agglomerated and formed larger flocs under the premise of maintaining high cell integrity. The terminal normalized flux was ascended from 0.048-0.072 to 0.711-0.956, and the fouling resistances were extraordinarily decreased. Due to the distinctive spiny structure and minimal electrostatic repulsion, Scenedesmus quadricauda was easier to form flocs, and its fouling was more readily mitigated. The fouling mechanism was remarkably altered through postponing the formation of cake filtration. The membrane interface characteristics including microstructures and functional groups firmly proved the fouling control efficiency. The reactive oxygen species (i.e., SO4â¢- and 1O2) generated through the principal reactions and Fe-Ca composite flocs played dominant roles in alleviating membrane fouling. Overall, the proposed pretreatment exhibits a brilliant application potential for enhancing UF in algal removal.
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Chlorella vulgaris , Purificação da Água , Ferro , Cálcio , Membranas Artificiais , Ultrafiltração , SulfitosRESUMO
OBJECTIVE: To assess the plasma selenium(Se) level of child-bearing-aged women and discuss the influence factor for low-Se level. METHODS: Using the muti-stage stratified and population proportional cluster random sampling method, 1881 child-bearing-aged women aged 18 to 44 years were selected from China Adult Chronic Disease and Nutrition Surveillance(2015) Data. The basic information of the subjects was collected by unified electronic questionnaires and equipments were used for field survey, measurement and record. Plasma Se concentration was detected by inductively coupled plasma mass spectrometry. Plasma low-Se level were assessed using lower limit of plasma/serum Se established by the Mayo Clinic Laboratory and our laboratory, respectively. Influence factors of low-Se level were analyzed by the multivariate logistic regression model. RESULTS: The M(P25, P75) plasma Se concentration for Chinese child-bearing-aged women was 89.52(74.21, 105.03)µg/L. Nationality, location, urban-rural type and education level difference had influence on plasma Se level in this population(P<0.05). According to the lower limit of plasma/serum Se concentration established by the Mayo clinical laboratories(<70 µg/L) and our laboratories(<73.81 µg/L), the low-Se rate were 20.47% and 24.51%, respectively. There were significantly differences in low-Se rate among nationality, location, urban-rural type, education level and marital status(P<0.05). The multivariate logistic regression model showed that location and urban-rural type had significant effects on low-Se rate of child-bearing-aged women(P<0.05). CONCLUSION: The plasma low-Se rate of Chinese women of childbearing age is relatively high and higher prevalence low-Se was found in western and central regions and rural areas in China.
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Selênio , Adulto , Feminino , Humanos , Povo Asiático , China/epidemiologia , População do Leste Asiático , Selênio/sangue , Inquéritos e Questionários , Adolescente , Adulto JovemRESUMO
Magnesium (Mg) is an essential nutrient that participates in various enzymatic reactions and regulates important biological functions. The distribution and reference ranges in China have not been reported in populations more than 45 years old. This study aimed to assess the magnesium status and determine the reference values of plasma Mg, Ca, and Ca/Mg ratios for China's population more than 45 years old. A total of 2101 people were randomly selected from the China Nutrition and Health surveillance (CNHS) (2015-2017), considering the regional types and monitoring points. Then, 337 healthy individuals were further selected by a series of strict inclusion criteria to explore the reference range. The plasma magnesium and calcium were tested by inductively coupled plasma mass spectrometry (ICP-MS). The suggested reference values for plasma Mg, Ca, and Ca/Mg ratios were 0.75-1.14 mmol/L, 2.17-3.64 mmol/L, and 2.36-3.66, respectively. Taking 0.75 mmol/L as the lower cut-off limit, the prevalence of Mg deficiency was 6.66%, and the average level of plasma magnesium was 0.88 mmol/L for populations older than 45 years in China. In conclusion, this study provides the magnesium status and reference ranges for plasma Mg, Ca, and Ca/Mg ratio for Chinese people over 45 years old. The results of the recommended reference ranges in this study were very similar to our published results in women of reproductive age. Thus, the reference range of plasma magnesium in different populations in China was further improved.
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Cálcio , Magnésio , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Valores de Referência , População do Leste Asiático , Cálcio da DietaRESUMO
Pyrazole carboxamides are a class of traditional succinate dehydrogenase inhibitors (SDHIs) that have developed into a variety of commercialized fungicides. In the present work, a series of novel 1,5-disubstituted-1H-pyrazole-4-carboxamide derivatives were designed and synthesized based on the active backbone of 5-trifluoromethyl-1H-4-pyrazole carboxamide. Bioassay results indicated that some target compounds exhibited excellent in vitro antifungal activities against six phytopathogenic fungi. Notably, the EC50 values of Y47 against Gibberella zeae, Nigrospora oryzae, Thanatephorus cucumeris, and Verticillium dahliae were 5.2, 9.2, 12.8, and 17.6 mg/L, respectively. The in vivo protective and curative activities of Y47 at 100 mg/L against G. zeae on maize were 50.7 and 44.2%, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis revealed that the large steric hindrance and electronegative groups on the 5-position of the pyrazole ring were important for the activity. The IC50 value of Y47 against succinate dehydrogenase (SDH) was 7.7 mg/L, superior to fluopyram (24.7 mg/L), which was consistent with the docking results. Morphological studies with fluorescence microscopy (FM) and scanning electron microscopy (SEM) found that Y47 could affect the membrane integrity of mycelium by inducing endogenous reactive oxygen species (ROS) production and causing peroxidation of cellular lipids, which was further verified by the malondialdehyde (MDA) content. Antifungal mechanism analysis demonstrated that the target compound Y47 not only had significant SDH inhibition activity but could also affect the membrane integrity of mycelium, exhibiting obvious dual action modes. This research provides a novel approach to the development of traditional SDHIs and their derivatives.
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Fungicidas Industriais , Fungicidas Industriais/farmacologia , Antifúngicos/farmacologia , Succinato Desidrogenase , Relação Estrutura-Atividade , Relação Quantitativa Estrutura-Atividade , Pirazóis/farmacologia , Simulação de Acoplamento MolecularRESUMO
Owing to their excellent properties, magnesium alloys are widely used in bone tissue engineering. However, considerable work has been conducted to control the degradation rate and improve the cytocompatibility of magnesium alloys. In this study, low-cost production introduced a new bone repair composite (PCL-nHAC/Mg-Ca), which was composed of nano-hydroxylapatite-collagen (nHAC), polycaprolactone (PCL) and Mg-Ca alloy substrate treated by micro- arc oxidation (MAO). The experimental results showed that compared with the Mg-Ca alloy treated by MAO alone, the PCL-nHAC/Mg-Ca composite has a porous structure and a slower degradation rate. Cell experiments showed that the PCL-nHAC/Mg-Ca composite had good biocompatibility and significantly enhanced the proliferation of the MC3T3-E1 cells. The rabbit skull defect model further proved that the PCL-nHAC/Mg-Ca composite could regulate the degradation rate of the Mg-Ca alloy and promote the formation of bone tissue. Histological analyses showed that the PCL-nHAC/Mg-Ca composite had good stability in vivo and could better accelerate bone formation.
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Durapatita , Osteogênese , Animais , Coelhos , Durapatita/química , Magnésio/química , Ligas/química , Colágeno/química , MonoaminoxidaseRESUMO
Microbial fuel cell (MFC) has been extensively studied as a biosensor for determining biochemical oxygen demand (BOD). The method for quantifying BOD by employing coulombic yield (Q) of a bio-electrochemical degradation process obtained from MFC biosensors is referred to as BODQ. The physical structures of anode materials greatly affect the sensitivity and accuracy of the biosensor. In this work, the effects of carbon cloth (CC) and carbon felt (CF) as anode substrate materials on the BODQ determination efficiencies were studied. The CF-MFC biosensor showed higher BODQ response than that of the CC-MFC within 25-400 mg L-1 BOD concentration range, and the test value was very close to the theoretical BOD. The difference is resulting from higher coulombic efficiency (CE) of CF-MFC (64.89-65.38 %) than CC-MFC (55.58-63.51 %). It should be noted that for water samples with low BOD concentrations the physical structures of anode materials play a leading role in CE. For synthetic wastewaters with 25 mg L-1 BOD, the CE of CF-MFC (65.38 %) was 17.63 % higher than that of CC-MFC (55.58 %). In contrast to the densely woven CC coated with thick biofilm, CF with loose carbon fiber and thin biofilm makes it good for organic diffusion and electron transportation, thus contributing to higher and more stable CE. These results indicate that the CF-MFC is more suitable for determining BODQ values over a wide concentration range. This work provides a useful strategy for selecting desirable MFC's anode material as the BOD biosensor. MFC biosensors with high-porosity biological anodes can obtain more accurate BOD test values.
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Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Carbono , Eletrodos , Técnicas Biossensoriais/métodos , Águas Residuárias/químicaRESUMO
Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disputed. We investigated 24 patients with gastric cancer in this study, using a 605-gene sequencing panel to sequence their plasma cfDNA and tumor tissue DNA. The mutation concordance between plasma cfDNA and tumor tissue DNA was 70.6% in stage IV gastric cancer and 30.2% in stage III gastric cancer, indicating insufficient mutation detection rates in stage III and early-stage cancer. When compared with total cfDNA load and blood tumor mutation burden (bTMB), the variant allele frequencies (VAF) of commonly mutated genes are highly accurate in representing disease burden. Further, VAF are a better prognostic indicator compared with serum biomarkers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP). The use of cfDNA in molecular profiling of patients allows prediction of patient survival and clinical response, as well as the development of personalized therapy regimens.
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Although several studies have shown the relationship between magnesium and diabetes, there are few studies regarding the association between magnesium status and prediabetes. This study aimed to examine the association between dietary magnesium intake and the risk of prediabetes in childbearing Chinese women (18−44 years). A total of 1981 participants without diabetes were randomly selected from China Nutrition and Health Surveillance (CNHS) in 2015 by considering the regional types and monitoring points, including 1420 normal fasting glucose (NFG) people and 561 prediabetes cases. The Food Frequency Questionnaire (FFQ) and inductively coupled plasma mass spectrometry (ICP-MS) measured dietary and plasma magnesium. The results of this study showed that dietary magnesium intake was inversely associated with fasting plasma glucose. For every 100 mg of magnesium intake, there was a 0.052 mmol/L (95% CI 0.019, 0.085) reduction in fasting plasma glucose (p = 0.002). Compared with the lowest intake quartile (<350.10 mg/day), the third and fourth quartiles (≥405.41 mg/day) reduced the odds risk of prediabetes (OR = 0.63, 95% CI 0.46, 0.88, p = 0.020) by approximately 37%. The dose-response curves for the association between magnesium intake and prediabetes followed an L shape. The odds ratio of prediabetes decreased significantly with increasing dietary Mg intake at less than 410 mg/day, and then the curve leveled off or slightly increased. This study found a negative association between dietary magnesium intake and prediabetes in childbearing Chinese women. The risk of prediabetes was reduced with increasing dietary magnesium intake, and the threshold value was 410 mg/day. This suggests that childbearing women also need to pay attention to their magnesium status.
Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Humanos , Feminino , Estado Pré-Diabético/epidemiologia , Magnésio , Glicemia/análise , China/epidemiologiaRESUMO
Hordeum californicum (H. californicum, 2n=2X=14, HcHc), one of the wild relatives of wheat (Triticum aestivum L.), harbors many desirable genes and is a potential genetic resource for wheat improvement. In this study, an elite line ND646 was selected from a BC4F5 population, which was developed using 60Co-γ irradiated wheat-H. californicum disomic addition line WJ28-1 (DA6Hc) as the donor parent and Ningchun 4 as the recurrent parent. ND646 was identified as a novel wheat-H. californicum 6HcS/6BL translocation line using genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), and H. californicum-specific expressed sequence tag (EST) markers. Further evaluation revealed that ND646 had excellent performance in several traits, such as a higher sedimentation value (SV), higher water absorption rate (WAR), and higher hardness index (HI). More importantly, it had more kernels per spike (KPS), a higher grain yields (GY), and good resistance to powdery mildew, leaf rust, and 2,4-D butylate (2,4-D). Its excellent phenotypic performance laid the foundation for further investigation of its genetic architecture and makes ND646 a useful germplasm resource for wheat breeding.