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Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 µM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.
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Atrazina , Herbicidas , Animais , Atrazina/metabolismo , Atrazina/toxicidade , Biomarcadores , Herbicidas/toxicidade , Humanos , Células MCF-7 , Metabolômica , TranscriptomaRESUMO
BACKGROUND: Inflammation-related diseases present a significant public health problem. Ginger is a flavoring spice and medicinal herb with anti-inflammatory activity. This study investigated the preventive effects of ginger extract (GE) and its main bioactive component, 6-gingerol (6G), on lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and liver injury in mice. RESULTS: GE and 6G were orally administered to mice for seven consecutive days before LPS administration. After 24 h, the mice were sacrificed. GE and 6G were found to significantly reverse LPS-induced inflammation in the mouse ileum by modifying the NF-κB pathway. They also alleviated apoptosis in the ileum by downregulating Bax and cytochrome c gene expression and by inhibiting the caspase-3 pathway. Through the aforementioned mechanisms, GE and 6G restored the intestinal barrier by increasing ZO-1 and claudin-1 protein expressions. Gut-derived LPS induced inflammation and apoptosis in the liver; these effects were markedly reversed through GE and 6G treatment. 6G was the most abundant component in GE, as evidenced through liquid chromatography-mass spectrometry, and accounted for >50% of total gingerols and shogaols in GE. CONCLUSION: The current results support the use of GE and 6G as dietary supplements to protect against gut-derived endotoxemia-associated inflammatory response and disorders. © 2021 Society of Chemical Industry.
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Anti-Inflamatórios/administração & dosagem , Catecóis/administração & dosagem , Álcoois Graxos/administração & dosagem , Enteropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Zingiber officinale/química , Animais , Apoptose/efeitos dos fármacos , Humanos , Enteropatias/imunologia , Enteropatias/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/lesões , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/lesões , Hepatopatias/imunologia , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
A novel filamentous, spore-forming, Gram-stain-positive bacterium, designated SCAWS-G2T, was isolated from red soil in Jiangxi Province, PR China. The strain grew at 25-45 °C and at pH 4.0-7.0, and was able to tolerate up to 50 mM Zn2+. The complete genome of strain SCAWS-G2T was a circular chromosome of ~11.34 Mb, which contained four 16S rRNA genes with three sequence types (0.4-0.8â% differences). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SCAWS-G2T formed a distinct lineage within the order Ktedonobacterales, showing <89.2â% sequence similarities to the recognized taxa of this order. The whole-genome based phylogenomic tree separated strain SCAWS-G2T from the recognized families within Ktedonobacterales. The genome-wide average nucleotide identity values between strain SCAWS-G2T and the related type strains were <68.2â%. The strain can also be differentiated from the recognized families by a number of phenotypic characteristics. The polar lipids of SCAWS-G2T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, seven unidentified glycolipids and one unidentified lipid. The peptidoglycan amino acids contained ornithine, glycine, glutamic acid and alanine, and the cell-wall sugars were mainly galactose and rhamnose. The major fatty acids were C16â:â1 2-OH, C16â:â0 and iso-C17â:â0. Based on all these data, we propose that strain SCAWS-G2T represents a novel genus and species, Ktedonosporobacter rubrisoli gen. nov., sp. nov., within the new family Ktedonosporobacteraceae fam. nov. of the order Ktedonobacterales. The type strain of Ktedonosporobacter rubrisoli is SCAWS-G2T (=CGMCC 1.16132T=DSM 105258T).
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Chloroflexi/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , Chloroflexi/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Adenosine triphosphate (ATP) biomolecules play critial roles in the biomineralization process during the formation of amorphous calcium phosphate composites (ACPC), and ACPC is an important drug carrier due to its significant advantages of biocompatibility and biodegradability. Hence, studying the behavior of ACPC nanodrug carriers is crucial to investigate the structural regulation of biomimetic minerals and calcium phosphate (CaP)-based drug delivery systems. However, it is difficult to probe these interactions using traditional characterization methods. In this paper, XANES analysis together with STXM successfully provided a method to reveal the interaction of ATP and drug molecules with individual mesoporous ACPC. We found that the adenosine and phosphate groups of ATP biomolecules coordinated with Ca2+ and played critical roles in the formation of ACPC; drug molecules with the -COOH groups were linked to Ca2+via carboxylic acid groups primarily by electrostatic interactions, and the N-containing ring structures within the drug molecules also coordinated with Ca2+.
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Trifosfato de Adenosina/química , Fosfatos de Cálcio/química , Doxorrubicina/química , Nanocompostos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Hemoglobinas/química , Tamanho da Partícula , Porosidade , Propriedades de Superfície , Espectroscopia por Absorção de Raios XRESUMO
BACKGROUND: Tele-monitoring (TM) is remote monitoring of individuals via info-communication technology, enabling them and their relatives or care-providers to recognize their health status conveniently. TM will be successful only if the individuals, often patients with medical conditions, are willing to accept and adopt it in their daily lives. This study aimed to determine the prevalence of willingness of patients with type 2 diabetes mellitus (T2DM) and/or hypertension towards the use of TM, and the factors influencing their uptake. METHODS: A cross-sectional survey was conducted at two public primary care clinics (polyclinics) in north-eastern Singapore, where TM had not been implemented. After the patients with T2DM and/or hypertension consented after fulfilling the eligibility criteria, they were first introduced to the concept of TM using pictogram and explanation by the investigators. Data on their demography, clinical parameters, technological literacy and acceptance of TM based on the Health Information Technology Acceptance Model (HITAM) were subsequently collected, computed, analyzed, followed by regression analyses to identify the factors associated with their willingness to use TM. RESULTS: Among 1125 eligible multi-ethnic Asian patients approached, 899 of them completed the assisted questionnaire survey, yielding a response rate of 79.9%. Their mean age was 58 ± 8 years, females 51.3% and Chinese 69.3%. Overall, 53.0% of the patients were willing to use TM. Personal beliefs on technology (OR = 3.54, 95%CI = 2.50-4.50, p < 0.001), prior technology utility (OR = 3.18, 95%CI = 1.57-6.42, p = 0.001), Patient's requirements to be accompanied (OR = 1.48, 95% CI = 1.054-2.082, P = 0.03) Cost considerations (OR = 2.96, 95% CI = 2.257-3.388, P < 0.01) and technological literacy (OR = 2.77, 95%CI = 2.05-3.38, p < 0.001) were associated with willingness to use TM. CONCLUSION: Slightly over half of the patients were willing to use TM. Factors such as age, ethnicity, technological literacy, beliefs and previous utility of technology of the patients have to be addressed before implementing TM in primary care.
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Diabetes Mellitus Tipo 2/prevenção & controle , Hipertensão/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Telemedicina , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , SingapuraRESUMO
Development of high-throughput sequencing stimulates a series of microbiome technologies, such as amplicon sequencing, metagenome, metatranscriptome, which have rapidly promoted microbiome research. Microbiome data analysis involves a lot of basic knowledge, software and databases, and it is difficult for peers to learn and select proper methods. This review systematically outlines the basic ideas of microbiome data analysis and the basic knowledge required to conduct analysis. In addition, it summarizes the advantages and disadvantages of commonly used software and databases used in the comparison, visualization, network, evolution, machine learning and association analysis. This review aims to provide a convenient and flexible guide for selecting analytical tools and suitable databases for mining the biological significance of microbiome data.
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Análise de Dados , Microbiota , Bases de Dados Factuais , Sequenciamento de Nucleotídeos em Larga Escala , Metagenoma , SoftwareRESUMO
Improving the stability of lead halide perovskite quantum dots (QDs) in a system containing water is the key for their practical application in artificial photosynthesis. Herein, we encapsulate low-cost CH3 NH3 PbI3 (MAPbI3 ) perovskite QDs in the pores of earth-abundant Fe-porphyrin based metal organic framework (MOF) PCN-221(Fex ) by a sequential deposition route, to construct a series of composite photocatalysts of MAPbI3 @PCN-221(Fex ) (x=0-1). Protected by the MOF the composite photocatalysts exhibit much improved stability in reaction systems containing water. The close contact of QDs to the Fe catalytic site in the MOF, allows the photogenerated electrons in the QDs to transfer rapidly the Fe catalytic sites to enhance the photocatalytic activity for CO2 reduction. Using water as an electron source, MAPbI3 @PCN-221(Fe0.2 ) exhibits a record-high total yield of 1559â µmol g-1 for photocatalytic CO2 reduction to CO (34 %) and CH4 (66 %), 38â times higher than that of PCN-221(Fe0.2 ) in the absence of perovskite QDs.
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A series of Ce3+ -activated K4 SrSi3 O9 materials emitting bright blue light under near-UV excitation was obtained by a facile solid-state reaction. The luminescence of Ce3+ -doped K4 SrSi3 O9 shows excellent thermal stability in a large temperature range. The detailed temperature/concentration-dependent luminescent properties of Ce3+ confirm that there are two different Ce3+ sites in K4 SrSi3 O9 :Ce3+ , and energy transfer from the high-energy Ce(1)3+ sites to the low-energy Ce(2)3+ sites was demonstrated to occur by electric dipole-dipole interaction. The maximum photoluminescence quantum yield of Ce3+ -doped K4 SrSi3 O9 can reach 56 %, and a UV-excited white LED device with low correlated color temperature (CCT=4617â K) and high color-rendering index (Ra =80) was fabricated with K4 SrSi3 O9 :Ce3+ .
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BACKGROUND/OBJECTIVES: Knowledge of and phobias about topical corticosteroids in parents of infants with eczema affect efficacy of eczema treatment. METHODS: We surveyed 300 parents of children with eczema using a questionnaire to investigate knowledge of and phobias about topical corticosteroids. RESULTS: Overall, 85.7% (n = 257) of children had used topical corticosteroids, with 12.8% (n = 33) of children having steroids applied for only 1-3 days per episode; 79.4% (n = 204) of patients discontinued topical steroid therapy immediately after improvement. Twenty-five percent (n = 75) of parents refused a prescription of steroid ointment, and 32.3% (n = 97) did not use the steroid ointment on their children despite having received a prescription. During steroid treatment, 95.7% (246) of parents were very concerned about the side effects of topical steroids. One hundred eight parents (42%) did not use a topical steroid ointment for recurrence of eczema because of concerns about using topical corticosteroids. CONCLUSION: Most parents of infants with eczema had excessive concerns about topical corticosteroids, leading to inadequate treatment of atopic dermatitis. In clinical practice, physicians should reinforce parents' understanding of steroid treatment for eczema and guide rational use of topical steroids for infantile eczema.
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Eczema/tratamento farmacológico , Glucocorticoides/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Pais/psicologia , Transtornos Fóbicos/epidemiologia , Administração Tópica , China , Feminino , Humanos , Lactente , Masculino , Inquéritos e QuestionáriosRESUMO
Millet bran, the by-product of millet processing industry, contains an abundance of phytochemicals, especially polyphenols. The main objective of this study was brewing antioxidant wine from millet bran, as well as the nutritional evaluation. The total polyphenol content of wine samples was determined by Folin-Ciocalteu colorimetric method, and the antioxidant capacity was evaluated by DPPH radical-scavenging capacity, Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP). Results showed that millet bran wine (MBW) contained as much as six times of total polyphenols compared with millet wine (MW), and performed considerably stronger antioxidant activity in DPPH, TEAC and FRAP assays. More than sixfold of total amino acids (AA) were found in MBW than in MW. Moreover, the indispensable AA and functional AA were also abundant in MBW. The major polyphenol compounds in MBW were identified using HPLC, including vanillic acid, syringic acid (SA), p-coumaric acid (CA) and ferulic acid (FA). They exhibited synergism in the antioxidant assays, especially the combinations of SA and CA, SA and FA. This study not only provides evidence for MBW as a nutraceutical with antioxidant activity, but also opens new avenues in the area of making comprehensive utilization of agricultural by-products.
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Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present. Therefore, the study aimed to establish a mouse SASP model to facilitate the research in the field. With this objective, we treated the INK4a-deficient mouse NIH-3T3 cells and the wildtype mouse embryonic fibroblasts (MEF) respectively with mitomycin C (MMC), an anticarcinoma drug which could induce DNA damage. The occurring of cell senescence was evaluated by cell morphology, ß-gal staining, integration ratio of EdU and Western blot. Quantitative RT-PCR and ELISA were used to detect the expression and secretion of SASP factors, respectively. The results showed that, 8 days after the treatment of NIH-3T3 cells with MMC (1 µg/mL) for 12 h or 24 h, the cells became enlarged and the ratios of ß-gal-positive (blue-stained) cells significantly increased, up to 77.4% and 90.4%, respectively. Meanwhile, the expression of P21 protein increased and the integration ratios of EdU significantly decreased (P < 0.01). Quantitative RT-PCR detection showed that the mRNA levels of several SASP genes, including IL-6, TNF-α, IL-1α and IL-1ß increased evidently. ELISA detection further observed an enhanced secretion of IL-6 (P < 0.01). On the contrary, although wildtype MEF could also be induced into senescence by MMC treatment for 12 h or 24 h, embodied by the enlarged cell volume, increased ratios of ß-gal-positive cells (up to 71.7% and 80.2%, respectively) and enhanced expression of P21 protein, the secretion of IL-6 displayed no significant change. Our study indicated that, although MMC could induce senescence in both mouse NIH-3T3 cells and wildtype MEF, only senescent NIH-3T3 cells displayed the canonical SASP phenomena. Current study suggested that senescent NIH-3T3 cells might be an appropriate in vitro SASP model of mouse cells.
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Senescência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Mitomicina/farmacologia , Animais , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dano ao DNA , Interleucina-6/metabolismo , Camundongos , Células NIH 3T3 , FenótipoRESUMO
Red soils, which are widely distributed in tropical and subtropical regions of southern China, are characterized by low organic carbon, high content of iron oxides, and acidity and, hence, are likely to be ideal habitats for acidophilic actinomycetes. However, the diversity and biosynthetic potential of actinomycetes in such habitats are underexplored. Here, a total of 600 actinomycete strains were isolated from red soils collected in Jiangxi Province in southeast China. 16S rRNA gene sequence analysis revealed a high diversity of the isolates, which were distributed into 26 genera, 10 families, and 7 orders within the class Actinobacteria; these taxa contained at least 49 phylotypes that are likely to represent new species within 15 genera. The isolates showed good physiological potentials for biosynthesis and biocontrol. Chemical screening of 107 semirandomly selected isolates spanning 20 genera revealed the presence of at least 193 secondary metabolites from 52 isolates, of which 125 compounds from 39 isolates of 12 genera were putatively novel. Macrolides, polyethers, diketopiperazines, and siderophores accounted for most of the known compounds. The structures of six novel compounds were elucidated, two of which had a unique skeleton and represented characteristic secondary metabolites of a putative novel Streptomyces phylotype. These results demonstrate that red soils are rich reservoirs for diverse culturable actinomycetes, notably members of the families Streptomycetaceae, Pseudonocardiaceae, and Streptosporangiaceae, with the capacity to synthesize novel bioactive compounds.
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Actinobacteria/isolamento & purificação , Actinobacteria/metabolismo , Metaboloma , Metabolismo Secundário , Microbiologia do Solo , Actinobacteria/classificação , Actinobacteria/genética , China , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Three neutrotolerant, acidophilic actinomycete strains, designated FXJ1.526, FXJ1.725(T) and FXJ1.726, were isolated from red soil collected from Liujiazhan, Jiangxi Province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the three strains clustered together and their closest relative was Streptomyces ferralitis CGMCC 4.1985(T) (98.9-99.0% similarity). Multilocus sequence analysis confirmed their relationship to S. ferralitis and separated these strains as representing a novel species. Mean DNA-DNA hybridization values among strains FXJ1.526, FXJ1.725(T) and FXJ1.726 were 81.6 ± 3.5-87.2 ± 3.8%, and the values between the three strains and S. ferralitis CGMCC 4.1985(T) were well below 70%. The three strains also shared several phenotypic characteristics that were distinct from the closely related species. They grew at 21-50 °C, at pH 4.0-9.0 (with an optimal pH of 5.0) and with 0-3% (w/v) NaCl, and the major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. On the basis of data from this polyphasic taxonomic study, it is proposed that strains FXJ1.526, FXJ1.725(T) and FXJ1.726 be classified as representatives of a novel species of the genus Streptomyces, with the name Streptomyces rubrisoli sp. nov. The type strain is FXJ1.725(T) ( = CGMCC 4.7025(T)= DSM 42083(T)).
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Streptomyces , Actinobacteria/genética , Actinomyces/genética , Actinomycetales/classificação , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Dados de Sequência Molecular , Hibridização de Ácido Nucleico/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio , Solo , Microbiologia do Solo , Streptomyces/classificaçãoRESUMO
Railway transportation has experienced significant growth worldwide, offering numerous benefits to society. Most railway accidents are caused by wheelset faults so it's significant to monitor wheelset conditions. Therefore, we need to collect wheelset images, repaint them, extract laser stripe centerlines, construct 3D contour, and measure their geometric parameters to judge the wheelset's conditions. Deep learning can fulfill the tasks satisfyingly because it's adaptable, robust, and generalize compared with traditional methods. To train the deep learning models effectively, we need rich and high-quality wheelset datasets. So far, there are no applicable public train wheelset datasets available, which greatly hinders the research on train wheelsets. Thus we construct a publicly available Wheelset Laser Image Dataset (WLI-Set). WLI-Set consists of four sub-datasets, Original, Inpainting, Segmentation, and Centerline. The dataset contains abundant annotated multiline laser stripe images that can facilitate the research on train wheelsets effectively.
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With the rapid development of modern industry, it is urgently needed to measure the biotoxicity of complex chemicals. Microbial electrochemical biotoxicity sensors are an attractive technology; however, their application is usually limited by their stability and reusability after measurements. Here, we improve their performance by encapsulating the electroactive biofilm with polydopamine (PDA), and we evaluate the improvement by different concentrations of heavy metal ions (Cu2+, Ag+, and Fe3+) in terms of inhibition ratio (IR) and durability. Results indicate that the PDA-encapsulated sensor exhibits a more significant detection concentration than the control group, with a 3-fold increase for Cu2+ and a 1.5-fold increase for Ag+. Moreover, it achieves 15 more continuous toxicity tests than the control group, maintaining high electrochemical activity even after continuous toxicity impacts. Images from a confocal laser scanning microscope reveal that the PDA encapsulation protects the activity of the electroactive biofilm. The study, thus, demonstrates that PDA encapsulation is efficacious in improving the performance of microbial electrochemical biotoxicity sensors, which can extend its application to more complex media.
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Biofilmes , Técnicas Biossensoriais , Técnicas Eletroquímicas , Indóis , Polímeros , Polímeros/química , Biofilmes/efeitos dos fármacos , Cobre/química , Metais Pesados , Prata/químicaRESUMO
The interaction between drug carrier and drug molecules is fundamental for the study of drug delivery, drug targeting, and drug release. Until now, little has been known about the interaction at the molecular level. X-Ray absorption near edge structure (XANES) spectroscopy is a sensitive tool for identifying this interaction. Herein, we report the use of calcium and silicon K-edge X-ray absorption near edge structure (XANES) spectroscopy to investigate how drug molecules interact with different functional groups in calcium silicate hydrate and anhydrous calcium silicate nanocarriers with different morphologies. Significant changes are observed in the XANES spectra after drug loading; ibuprofen (IBU) loading leads to the ordering of silicates locally and there is loss of hydrates during the IBU loading processes.
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Compostos de Cálcio/química , Portadores de Fármacos/química , Ibuprofeno/química , Nanopartículas/química , Silicatos/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Espectroscopia por Absorção de Raios XRESUMO
By virtue of the high energy conversion efficiency and compact facility, proton exchange membrane water electrolysis (PEMWE) is a promising green hydrogen production technology ready for commercial applications. However, catalyst stability is a challenging but often-ignored topic for the electrocatalyst design, which retards the device applications of many newly-developed electrocatalysts. By defining catalyst stability as the function of activity versus time, we ascribe the stability issue to the evolution of catalysts or catalyst layers during the water electrolysis. We trace the instability sources of electrocatalysts as the function versus time for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in acid and classify them into internal and external sources. Accordingly, we summarize the latest studies for stability improvements into five strategies, i. e., thermodynamic stable active site construction, precatalyst design, support regulation, superwetting electrode fabrication, and catalyst-ionomer interface engineering. With the help of ex-situ/ in-situ characterizations and theoretical calculations, an in-depth understanding of the instability sources benefits the rational development of highly active and stable HER/OER electrocatalysts for PEMWE applications.
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Developing highly active and stable oxygen evolution reaction (OER) catalysts for water electrolysis remains a great challenge. A self-supported Ir nanocatalyst was prepared via a self-assembly method. Its porous structure and residual metal incorporation contributed to its high activity and stability for the OER in acid.
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Background: The coronavirus disease 2019 (COVID-19) has been spreading astonishingly and caused catastrophic losses worldwide. The high mortality of severe COVID-19 patients is an serious problem that needs to be solved urgently. However, the biomarkers and fundamental pathological mechanisms of severe COVID-19 are poorly understood. The aims of this study was to explore key genes related to inflammasome in severe COVID-19 and their potential molecular mechanisms using random forest and artificial neural network modeling. Methods: Differentially expressed genes (DEGs) in severe COVID-19 were screened from GSE151764 and GSE183533 via comprehensive transcriptome Meta-analysis. Protein-protein interaction (PPI) networks and functional analyses were conducted to identify molecular mechanisms related to DEGs or DEGs associated with inflammasome (IADEGs), respectively. Five the most important IADEGs in severe COVID-19 were explored using random forest. Then, we put these five IADEGs into an artificial neural network to construct a novel diagnostic model for severe COVID-19 and verified its diagnostic efficacy in GSE205099. Results: Using combining P value < 0.05, we obtained 192 DEGs, 40 of which are IADEGs. The GO enrichment analysis results indicated that 192 DEGs were mainly involved in T cell activation, MHC protein complex and immune receptor activity. The KEGG enrichment analysis results indicated that 192 GEGs were mainly involved in Th17 cell differentiation, IL-17 signaling pathway, mTOR signaling pathway and NOD-like receptor signaling pathway. In addition, the top GO terms of 40 IADEGs were involved in T cell activation, immune response-activating signal transduction, external side of plasma membrane and phosphatase binding. The KEGG enrichment analysis results indicated that IADEGs were mainly involved in FoxO signaling pathway, Toll-like receptor, JAK-STAT signaling pathway and Apoptosis. Then, five important IADEGs (AXL, MKI67, CDKN3, BCL2 and PTGS2) for severe COVID-19 were screened by random forest analysis. By building an artificial neural network model, we found that the AUC values of 5 important IADEGs were 0.972 and 0.844 in the train group (GSE151764 and GSE183533) and test group (GSE205099), respectively. Conclusion: The five genes related to inflammasome, including AXL, MKI67, CDKN3, BCL2 and PTGS2, are important for severe COVID-19 patients, and these molecules are related to the activation of NLRP3 inflammasome. Furthermore, AXL, MKI67, CDKN3, BCL2 and PTGS2 as a marker combination could be used as potential markers to identify severe COVID-19 patients.
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COVID-19 , Inflamassomos , Humanos , Inflamassomos/genética , Ciclo-Oxigenase 2 , Algoritmo Florestas Aleatórias , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Proteínas Proto-Oncogênicas c-bcl-2RESUMO
BACKGROUND: Diabetes-related distress (DRD) is a negative emotional state related to the burden of living with diabetes mellitus. It has been associated with poor self-care and glycaemic control. This cross-sectional study aimed to examine the factors associated with DRD among urban Asian patients with poorly controlled type-2 diabetes mellitus (T2DM) in primary care in Singapore. The factors included demographics, diabetes history, medical co-morbidities, mood disorders and social history. METHODS: Patients with T2DM and HbA1c of 8% or more were recruited from 2 public primary care centres in Singapore. They were administered a questionnaire survey to identify DRD based on the Problem Area In Diabetes (PAID) scale. Their anxiety and depression were screened using GAD-7 and PHQ-9, and quality of life (QOL) measured using the EQ-5D-5L. Their clinical data, including HbA1c, comorbidities and medications, were extracted from the electronic medical records. RESULTS: Among the 356 subjects, the prevalence of DRD was 17.4%. DRD was significantly associated with younger age (AOR (95% CI) = 0.93 (0.89-0.97), p = 0.001), ex-smoker status (AOR (95% CI) = 22.30 (2.43-204.71), p = 0.006) and history of kidney disease (AOR (95% CI) = 3.41 (1.39-8.35), p = 0.007). Those who screened positive for depression (AOR (95% CI) = 4.98 (1.19-20.86), p = 0.028) were almost five times more likely to have DRD. Quality of life was lower among those with DRD (EQ5D index score AOR (95% CI) = 0.11 (0.01-0.97), p = 0.047), who also tended to feel that diabetes pharmacotherapy interfered with their normal life (AOR (95% CI) = 2.89 (1.38-6.08), p = 0.005). CONCLUSION: About 1 in 6 patients with poorly controlled T2DM had DRD. Younger age, ex-smoker status, history of kidney disease, and those with depressive symptoms were most at risk.