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Solid-state materials with efficient room-temperature phosphorescence (RTP) emission have been widely used in materials science, and organic RTP-emitting systems with heavy-metal doping in aqueous solutions have attracted much attention in recent years. A novel supramolecular interaction was induced by host-guest assembly using cucurbit[7]uril (Q[7]) as the host and brominated naphthalimide phosphor as the guest. This interaction was further enhanced through synergistic chelation stimulated by analytical silver ion complexation. This approach facilitated the system's structural rigidity, intersystem crossing, and oxygen shielding. We achieved deep red phosphorescence emission in aqueous solution and ambient conditions along with quantitative determination of silver ions. The new complex exhibited good reversible thermoresponsive behavior and was successfully applied for the first time to target phosphorescence imaging of silver ions in the mitochondria of A549 cancer cells. These results are beneficial for constructing novel RTP systems with stimulus-responsive luminescence in aqueous solution, contributing to future research in bioimaging, detection, optical sensors, and thermometry materials.
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The separation of phenylenediamine (PDA) isomers is crucial in the field of chemical manufacturing. Herein, we presented a strategy for the separation of PDA isomers (para-phenylenediamine, p-PDA; meta-phenylenediamine, m-PDA; ortho-phenylenediamine, o-PDA) using four supramolecular framework materials of ns-cucurbit[10]uril (ns-Q[10]), (1) ns-Q[10](Cd), (2) ns-Q[10](Mn), (3) ns-Q[10](Cu), (4) ns-Q[10](Pb). Our findings indicated that these supramolecular framework materials of ns-Q[10] showed remarkable selectivity for para-phenylenediamine (p-PDA) in p-PDA, m-PDA, and o-PDA mixtures, respectively. The variations in selectivity observed in these four single-crystal structures arose from variations in the thermodynamic stabilities and binding modes of the host-guest complexes. Importantly, the supramolecular framework based on ns-Q[10] exhibited selective accommodation of p-PDA over its isomers. This study highlighted the practical application of ns-Q[10] in effectively separating PDA isomers and demonstrated the potential utility of ns-Q[10] in isolating other organic molecules.
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Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFßR2 levels. In white adipose tissue, a set of lipogenesis-related genes, Srebp1, Fas, and Scd-1 were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of Tfam, Cd137, Tmem26, Ucp1 expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways.
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Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Resistência à Insulina , Losartan/farmacologia , Animais , Glucose/metabolismo , Intolerância à Glucose/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metabolismo dos Lipídeos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Obesos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: With the advancement of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been deployed to a wide range of clinical scenarios. Rapid and accurate classification of drug-resistant Mycobacterium tuberculosis (MTB) would be advantageous in reducing the amplification of additional drug resistance and disease transmission. METHODS: In this study, a long-read sequencing approach was subjected to the whole-genome sequencing of clinical MTB clones with susceptibility test profiles, including isoniazid (INH) susceptible clones (n = 10) and INH resistant clones (n = 42) isolated from clinical specimens. Non-synonymous variants within the katG or inhA gene associated with INH resistance was identified using Nanopore sequencing coupled with a corresponding analytical workflow. RESULTS: In total, 54 nucleotide variants within the katG gene and 39 variants within the inhA gene associated with INH resistance were identified. Consistency among the results of genotypic profiles, susceptibility test, and minimal inhibitory concentration, the high-INH resistance signature was estimated using the area under the receiver operating characteristic curve with the existence of Ser315Thr (AUC = 0.822) or Thr579Asn (AUC = 0.875). CONCLUSIONS: Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones.
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Antituberculosos/farmacologia , Farmacorresistência Bacteriana/genética , Genoma Bacteriano , Isoniazida/farmacologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Fenótipo , Sequenciamento Completo do GenomaRESUMO
Hypoxia and hepatosteatosis microenvironments are fundamental traits of nonalcoholic fatty liver disease (NAFLD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with NAFLD, whereas the route and regulation of lipid droplets (LDs) and macrophage polarization related to systemic inflammation in NAFLD is unknown. Losartan is an angiotensin II receptor antagonist, that approved portal hypertension and related HIF-1α pathways in hepatic injury models. Here, we show that losartan in a murine model of NAFLD significantly decreased hepatic de novo lipogenesis (DNL) as well as suppressed lipid droplets (LDs), LD-associated proteins, perilipins (PLINs), and cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector (CIDE) family in liver and epididymal white adipose tissues (EWAT) of ob/ob mice. Obesity-mediated macrophage M1 activation was also required for HIF-1α expression in the liver and EWAT of ob/ob mice. Administration of losartan significantly diminishes obesity-enhanced macrophage M1 activation and suppresses hepatosteatosis. Moreover, HIF-1α-mediated mitochondrial dysfunction was reversed in ob/ob mice treated with losartan. Together, the regulation of HIF-1α controls LDs protein expression and macrophage polarization, which highlights a potential target for losartan in NAFLD.
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Fígado Gorduroso/prevenção & controle , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Losartan/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/complicações , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos ObesosRESUMO
Heavy metal and metalloid (HMM) contamination of the water environment caused by mining activities is a great challenge to the global mining industry. HMMs released by various mines could easily enter the surrounding environment and pose serious threats to human health. Although the HMM pollution of surface water in various mines has been widely researched, relevant studies on the effects of mining activities on the surface water of hard-rock-type Li mines are scarce. Herein, a total of 81 water samples were collected from Jiajika mine for the first time, the largest hard-rock-type Li mine in Asia. The physical parameters and concentrations of HMMs and major ions of the samples were analyzed to evaluate the water quality and HMM level of surface water. Results showed that (1) most of the parameters analyzed adhered to the strictest guidelines of Chinese surface waters and the drinking water guidelines of WHO, except Mn, Pb, and As of a few samples from tailings-affected areas and Li-bearing areas; (2) mineral tailings obviously increased the pH and decreased the dissolved oxygen (DO) of the surrounding surface waters; (3) the highest concentrations of As (5.58 µg/L), Zn (81.8 µg/L), Ba (5.26 µg/L), and Co (0.33 µg/L) were observed around the tailings reservoir, whereas the highest concentrations of Cr (1.5 µg/L), Mn (380 µg/L), Pb (28.4 µg/L), and V (3.16 µg/L) were observed in Li-bearing areas; and (4) according to the statistical results, the concentrations of As, Cr, Ni, and V in surface water were mainly affected by mining activities, whereas those of Cu, Zn, Ba, Co, and Pb were dominantly affected by natural processes. These results provide useful information about water quality in relation to Li mining and can help the government make reasonable decisions regarding hard-rock-type Li resource exploitation activities.
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Metais Pesados , Poluentes do Solo , Poluentes Químicos da Água , Ásia , China , Monitoramento Ambiental , Humanos , Lítio , Metais Pesados/análise , Poluentes do Solo/análise , Poluentes Químicos da Água/análiseRESUMO
Mycobacterium tuberculosis (M.tb) infection in lung causes pulmonary fibrosis, which leads to the irreversible reduction of pulmonary function. Fibrotic protein connective tissue growth factor (CTGF) expression has been confirmed to play a crucial role in lung fibrosis. However, the underlying signal pathway and effect of M.tb on CTGF expression in human lung fibroblasts are unclear. Our results revaled that M.tb caused time- and concentration-dependent increases in CTGF expression in human lung fibroblasts. A mechanistic investigation revealed that M.tb induced CTGF expression through TLR2 but not TLR4. The promoter activity assay indicated that M.tb-induced CTGF activity was mainly controlled by the promoter region at -747 to -184 bp, which contained signal transducer and activator of transcription 3 and activator protein 1 (AP-1) binding sites. Moreover, curcumin (AP-1 inhibitor) restrained M.tb-induced CTGF expression. M.tb also induced increases in AP-1 luciferase activity and DNA binding activity of c-Jun and c-Fos on the CTGF promoter. Furthermore, the knockdown of c-Jun by small interfering RNA attenuated M.tb-induced CTGF expression and AP-1 luciferase activity. A JNK inhibitor (SP600125) and a JNK dominant-negative mutant suppressed M.tb-induced CTGF expression. We also discovered that M.tb could induce the phosphorylation of JNK and c-Jun. Furthermore, SP600125 inhibited M.tb-induced c-Jun phosphorylation and AP-1- luciferase activity. M.tb-induced fibronectin expression was inhibited by anti-CTGF antibody. These results demonstrate that M.tb is activated through TLR2 to induce JNK activation, further increasing the DNA binding activity of c-Jun and c-Fos and finally inducing CTGF expression and extracellular matrix production.-Lee, H.-S., Hua, H.-S., Wang, C.-H., Yu, M.-C., Chen, B.-C., Lin, C.-H. Mycobacterium tuberculosis induces connective tissue growth factor expression through the TLR2-JNK-AP-1 pathway in human lung fibroblasts.
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Fator de Crescimento do Tecido Conjuntivo/biossíntese , Fibroblastos/metabolismo , Pulmão/metabolismo , MAP Quinase Quinase 4/metabolismo , Mycobacterium tuberculosis/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Fator de Transcrição AP-1/metabolismo , Tuberculose Pulmonar/metabolismo , Antracenos/farmacologia , Linhagem Celular , Fator de Crescimento do Tecido Conjuntivo/genética , Fibroblastos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/patologia , MAP Quinase Quinase 4/antagonistas & inibidores , Elementos de Resposta , Tuberculose Pulmonar/patologiaRESUMO
Physalin B (PB) is one of the major constituents of Physalis alkekengi var. franchetii, a well-known Chinese traditional herb. In this study, we demonstrated for the first time that PB exhibits significant antiproliferative and apoptotic activity in A549 human lung cancer cells in a concentration-dependent and time-dependent manner. Flow cytometric analyses indicated that PB-induced G2/M arrest through down-regulation of cyclin B1 and cell division control protein cyclin-dependent kinase 1, and up-regulation of p21. The reduction in the level of cyclin B1/cyclin-dependent kinase 1 complex down-regulated oxidative phosphorylation multisubunit activity to reduce mitochondrial energetic homeostasis. Moreover, defects in mitochondrial ATP synthesis and mitochondrial membrane potential were found in PB-treated cell lines. These abnormalities led to an increase in intracellular superoxide and apoptosis. Thus, as an inhibitor of mitochondrial energetic homeostasis, PB demonstrates potent antitumor activities and may be developed as an alternative therapeutic agent against non-small-cell lung cancer.
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Apoptose , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Mitocôndrias/patologia , Secoesteroides/farmacologia , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Mitocôndrias/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in numerous biological processes. However, the role of miRNAs in skin color determination in fish has not been completely determined. Here, we identified that 13 miRNAs are differentially expressed between red and white skin. The analysis of miRNA spatial and temporal expression patterns suggests that miR-429 is a potential regulator of skin pigmentation. miR-429 silencing results in an obvious change in skin pigmentation. Bioinformatics analysis and a luciferase reporter assay show that miR-429 directly regulates expression of Foxd3 by targeting its 3'-untranslated (3'-UTR) region. miR-429 silencing leads to a substantial increase in the expression of Foxd3 in vivo, thereby repressing the transcription of MITF and its downstream genes, such as TYR, TYRP1 or TYRP2. These findings would provide a novel insight into the determination of skin color in fish.
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Carpas/metabolismo , MicroRNAs/metabolismo , Fenômenos Fisiológicos da Pele/genética , Pigmentação da Pele/genética , Animais , Carpas/genética , MicroRNAs/biossíntese , MicroRNAs/genéticaRESUMO
A supramolecular fluorescence probe has been developed using a symmetrical tetramethyl cucurbit[6]uril (TMeQ[6]) and a styryl derivative (SPy) with a host-guest ratio of 2:1. The introduction of paraquat (PQ) competes with SPy for the TMeQ[6] cavity, resulting in fluorescent quenching. The addition of 17 common herbicides and ions had negligible effects on the fluorescence quenching, indicating that the 2TMeQ[6]/SPy complex exhibits excellent selectivity in detecting PQ. The detection limit was found to be 4.62 × 10-7 M. More importantly, the probe was engineered to detect paraquat in river water by examining post-treatment samples and noting alterations in fluorescence color. The red to blue (R/B) intensity ratio is subsequently calculated to ascertain the PQ concentration. Experimental trials conducted on river water samples yielded recovery rates between 98.21 % and 108 %, with a relative standard deviation of less than 5 %. By pairing this with a smartphone-based colorimetric analysis application, we can facilitate portable PQ detection, enabling efficient and convenient monitoring across various locations.
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Carbonaceous aerosol is an important component of atmospheric fine particulates ï¼PM2.5ï¼ that has an important effect on global climate change, atmospheric visibility, regional air quality, and human health. In order to investigate the long-term change characteristics of carbonaceous aerosols under the background of emission reduction, the concentrations of organic carbon ï¼OCï¼, elemental carbon ï¼ECï¼ in PM2.5 samples, and volatile organic compounds ï¼VOCsï¼ in Chengdu from 2018 to 2021 and the corresponding meteorological factors were obtained through real-time online monitoring. The results showed that the average ρï¼OCï¼ and ρï¼ECï¼ during the monitoring period were ï¼10.9 ±5.7ï¼ µg·m-3 and ï¼2.6 ±1.9ï¼ µg·m-3, accounting for 25.2% and 6.0% of PM2.5, respectively, and the average ρï¼SOCï¼ was ï¼5.7 ±3.3ï¼ µg·m-3, accounting for 52.9% of OC. The concentrations of OC, EC, and PM2.5 showed a downward trend from 2018 to 2020 [PM2.5ï¼ The concentration of average annual decrease was -7.1 µg·ï¼m3·aï¼ -1, with an average annual decrease of -14.6 %·a-1ï¼ OCï¼ -1.7 µg·ï¼m3·aï¼-1, -14.2 %·a-1ï¼ ECï¼ -0.1 µg·ï¼m3·aï¼-1, -4.4 %·a-1], and the concentrations of each pollutant in 2021 rebounded in different ranges compared with those in 2020. The concentrations of PM2.5 and OC were as followsï¼ winter > spring > autumn > summer, and the concentrations of EC were as followsï¼ winter > autumn > spring > summer. The proportions of OC and EC were higher in summer and autumn than in other seasons, with the average proportions of 26.8% and 6.9%, respectively. With the aggravation of the pollution level, OC, EC, and SOC concentrations gradually increased, but the proportions in PM2.5 showed a gradual downtrend, indicating that the control factor of PM2.5 pollution in Chengdu was not the carbon component. Source apportionment results showed that carbonaceous aerosols in Chengdu were mainly affected by motor vehicles, industrial sources, biomass combustion sources, and VOCs secondary reaction. From 2019 to 2021, EC was affected by the characteristic components of motor vehicles and decreased yearly. OC and EC were affected by VOCs more in spring and autumn than in other seasons. VOCs emission management should be increased in spring and autumn to reduce the impact of secondary reaction.
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OBJECTIVE: To study the role of arginase-1 (Arg-1) expression in differential diagnosis of hepatocellular carcinoma (HCC), Arg-1 staining pattern in clear cell neoplasm (HCC and non-HCC) and Arg-1 expression in non-hepatocellular tumors. METHODS: Seventy-eight cases of HCC (including 8 cases of clear cell type and 70 cases of non- clear cell type) and 246 cases of non-hepatocellular neoplasms (including 29 cases of metastatic tumors such as breast cancer, nasopharyngeal carcinoma and neuroendocrine carcinoma, 77 cases of tumors with clear cell changes such as malignant melanoma, clear cell renal cell carcinoma and alveolar soft part sarcoma, and 140 cases of other types of tumors such as ovarian endometrioid adenocarcinoma, pituitary tumor and thyroid papillary carcinoma) were studied.Immunohistochemical study for Arg-1 was performed on the paraffin-embedded tumor tissue. RESULTS: In HCC, Arg-1 demonstrated both cytoplasmic and nuclear staining, with an overall sensitivity of 96.2% (75/78).In well, moderately and poorly differentiated HCC, the sensitivity was 15/15, 100% (41/41) and 86.4% (19/22), respectively. That was in contrast to negative staining for Arg-1 in all the 29 cases of metastatic tumors studied. The sensitivity, specificity, positive predictive value and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors was 96.2%, 100%, 100% and 90.6%, respectively. Cytoplasmic and membranous staining was observed in clear cell type of HCC. The overall sensitivity of Arg-1 expression in the 77 cases of tumors with clear cell changes was 14.3% (11/77), including 8/15 for malignant melanoma, 2/4 for ovarian clear cell carcinoma and 1/1 gall bladder adenocarcinoma with clear cell component.In malignant melanoma and ovarian clear cell carcinoma, only cytoplasmic staining was demonstrated. There was no expression of Arg-1 in the 140 cases of other tumor types studied. CONCLUSIONS: Arg-1 is a sensitive and specific marker for HCC.It is a potentially useful immunohistochemical marker in distinguishing HCC from metastatic tumors. Though also expressed in malignant melanoma and ovarian clear cell carcinoma, Arg-1 shows a different staining pattern as compared with that in HCC.
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Arginase/metabolismo , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Adenocarcinoma/enzimologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Neoplasias da Vesícula Biliar/enzimologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Melanoma/enzimologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/enzimologia , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Presumptive tuberculosis (TB) cases commonly had two to three sputum examinations in Taiwan. The incremental yield of serial sputum examinations has not been assessed before. METHODS: In a pragmatic trial, presumptive TB patients with a frontline nucleic acid amplification test (NAAT) were classified as group A. Those without a frontline NAAT were randomized into group B frontline NAAT as intervention, and group C usual care. We investigated expected incremental yields and the number of examinations required for detection of one additional TB case from each serial sputum smear and culture. RESULTS: Of 6835 presumptive TB cases, 395 (5.8%) were smear positive for acid-fast bacilli, and 195 (2.8%) culture positive for M tuberculosis. The expected incremental yield from a third smear was 3.5% and examination of 1712 (95% credibility interval 586-4706) third smears was required to detected one additional TB case. Sensitivity of one smear with an NAAT in group B was 46.8% (95% confidence interval 32.1%-61.9%), and that of two smears in Group C 40.0% (95% confidence interval 25.7%-55.7%). The expected incremental yield from a third culture was 8.4%, and the number of third cultures required to detect one additional TB case was 394 (95% credibility interval 231-670). CONCLUSIONS: The incremental yield of the third sputum smear was negligible. It may be reasonable to perform an NAAT, smear and culture on the first specimen and culture alone on the second. The utility of the third serial culture for the detection of additional TB case is debatable.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Humanos , Escarro , Taiwan , Tuberculose Pulmonar/diagnóstico , Tuberculose/diagnóstico , Mycobacterium tuberculosis/genética , Sensibilidade e EspecificidadeRESUMO
Fluorescent carbon quantum dots (CQDs) were synthesized from cucurbit[7]uril (Q[7]) and 2,2-bis(hydroxymethyl)propionic (DMPA) by a hydrothermal method. The Q[7]-DMPA complex was confirmed by X-ray crystallography. The CQDs showed blue fluorescence, photostability, and ionic strength stability. They were used to detect histamine with a low limit of 2.33 × 10-6 M.
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Histamina , Pontos Quânticos , Carbono/química , Pontos Quânticos/química , Corantes Fluorescentes/químicaRESUMO
OBJECTIVE: To study the expression of ß-catenin protein and the status of loss of heterozygosity (LOH) on chromsome 10q in medulloblastoma, with clinical correlation. METHODS: Immunohistochemical study for ß-catenin protein was carried out in 50 cases of medulloblastoma encountered in the First Affiliated Hospital of Xinjiang Medical University during the period from 2002 to 2011, including 32 cases of classic medulloblastoma, 13 cases of desmoplastic medulloblastoma and 5 cases of medulloblastoma with extensive nodularity. The status of LOH on 10q was also detected by fluorescence in-situ hybridization. The clinicopathologic characteristics and prognostic parameters were studied by Kaplan-Meien and Cox analysis. RESULTS: The rates of expression of ß-catenin protein in classic medulloblastoma, desmoplastic medulloblastoma and medulloblastoma with extensive nodularity were 53.1% (17/32), 4/13 and 1/5, respectively. The rate of LOH on 10q was 33.3% (8/24) in classic medulloblastoma and 2/11 in desmoplastic medulloblastoma. There was no statistically significant difference between the two tumor types. Univariate analysis showed that the expression of ß-catenin protein (P = 0.022), lack of LOH on 10q (P = 0.020), extensiveness of tumor resection (P < 0.01), radiotherapy (P = 0.002) and chemotherapy (P < 0.01) represented important prognostic factors. CONCLUSIONS: Medulloblastoma with expression of ß-catenin protein and without LOH on 10q carries a better prognosis. Assessment of these parameters is helpful in evaluating prognosis and subsequent patient management.
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Neoplasias Cerebelares , Cromossomos Humanos Par 10/genética , Perda de Heterozigosidade , Meduloblastoma , beta Catenina/metabolismo , Adolescente , Adulto , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Meduloblastoma/genética , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Meduloblastoma/cirurgia , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Adulto JovemRESUMO
The rapid development of digital technologies has transformed the world but can be a double-edged sword. We study the interaction of important variables that affect individual news reporters' performance in which digital technology is the dominant feature. A multilevel model illustrates how transactive memory and job competence affect individual performance. The empirical study includes data from 19 teams of news reporters and 211 valid survey responses, applying hierarchical linear modeling to analyze the data. The results indicate that transactive memory and technology competence help to improve a reporter's job performance. More importantly, teamwork competence fully mediates the relationships. Our findings thus suggest that teamwork competence is the core skill. Neither technology competence nor transactive memory alone translates directly into enhanced individual performance.
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Drug resistance in Mycobacterium tuberculosis (MTB) has long been a serious health issue worldwide. Most drug-resistant MTB isolates were identified due to treatment failure or in clinical examinations 3~6 months postinfection. In this study, we propose a whole-genome sequencing (WGS) pipeline via the Nanopore MinION platform to facilitate the efficacy of phenotypic identification of clinical isolates. We used the Nanopore MinION platform to perform WGS of clinical MTB isolates, including susceptible (n = 30) and rifampin- (RIF) or rifabutin (RFB)-resistant isolates (n = 20) according to results of a susceptibility test. Nonsynonymous variants within the rpoB gene associated with RIF resistance were identified using the WGS analytical pipeline. In total, 131 variants within the rpoB gene in RIF-resistant isolates were identified. The presence of the emergent Asp531Gly or His445Gln was first identified to be associated with the rifampin and rifabutin resistance signatures of clinical isolates. The results of the minimum inhibitory concentration (MIC) test further indicated that the Ser450Leu or the mutant within the rifampin resistance-determining region (RRDR)-associated rifabutin-resistant signature was diminished in the presence of novel mutants, including Phe669Val, Leu206Ile, or Met148Leu, identified in this study. IMPORTANCE Current approaches to diagnose drug-resistant MTB are time-consuming, consequently leading to inefficient intervention or further disease transmission. In this study, we curated lists of coding variants associated with differential rifampin and rifabutin resistant signatures using a single molecule real-time (SMRT) sequencing platform with a shorter hands-on time. Accordingly, the emerging WGS pipeline constitutes a potential platform for efficacious and accurate diagnosis of drug-resistant MTB isolates.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Rifabutina/farmacologia , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a prevalent issue and a consequence of metabolic syndrome impact on human health. Both of anti-atherosclerosis and anti-hepatic fibrosis capabilities of herbal medicine Ger-Gen-Chyn-Lian-Tang (GGCLT) has attracted attention, but their molecular regulatory mechanisms in a NAFLD model have not been elucidated. The aim of the present study was to explore the bioactivity of db/db mice following treatment with GGCLT. METHODS: NAFLD phenotype of db/db mice were treated with GGCLT and lipogenesis, mitochondria dysfunction, mitophagy, macrophage polarization and adipose tissue browning were then evaluated using qRT-PCR and/or Western blot analysis, immunofluorescence, and immunohistochemistry assays, respectively. RESULTS: GGCLT not only decreased serum levels of TG and free fatty acids, but glucose and insulin tolerance test in db/db mice. In parallel, GGCLT reduced lipogenesis and hypoxia-inflammation cascades in NAFLD progression. GGCLT reduced lipid accumulation and was accompanied by the enhanced mitochondria biogenesis, M2 macrophage, and decreased M1 macrophage. The latter two events contributing to the anti-inflammation are resulting from mitochondria dynamics, and the lipotoxicity lowering effect of GGCLT of NAFLD mice is mediated by promoting mitophagy in Parkin-dependent and -independent pathways, by mitochondrial fusion over fission manner. GGCLT also inactivated lipogenesis and decreased lipid accumulation in epididymal white adipose tissue with a higher M2/M1 macrophage ratio. CONCLUSIONS: Besides in the liver, modulating of mitochondrial biogenesis and adipose tissue browning were characterized by increased Tmem26, Tfam, and Prdm16 expression by GGCLT in EWAT also contributes to the beneficial action in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Animais , Antioxidantes/metabolismo , Medicina Herbária , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitofagia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Biogênese de OrganelasRESUMO
NMHCs concentrations and VOCs components were sampled from 12 typical catering units in Sichuan Province. Combined with literature data, the cooking source profile containing 117 VOCs was established comprehensively, and the NMHCs emission factors were obtained. Based on the bottom-up research method, the volatile organic compounds emission inventory of cooking sources in Sichuan Province was established. The results showed that the oxygen and alkane groups were the most important components for Sichuan cuisine, barbecue, and canteen, and the total proportion of the two groups was greater than 75%. The main VOCs species were ethanol, formaldehyde, ethane, hexanal, ethylene, 1,3-butadiene, and acrolein. Oxygen-containing components contributed the most to OFP, followed by olefin. The major OFP contributors were formaldehyde, ethylene, ethanol, 1,3-butadiene, acrolein, hexanal, etc. In 2019, the VOCs emissions and OFP values of cooking sources in Sichuan Province were 32kt and 141kt, respectively, accounting for approximately 5% of the anthropogenic VOCs emissions and OFP values in Sichuan Province. The VOCs emission from cooking may have an important contribution to ozone formation, which means more attention should be paid to cooking.
Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Culinária , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Patients receiving hemodialysis (HD) are at risk of TB development. IGRA-positive patients showed significant decrease in quantitative IGRA result with alterations in CD3+CD4+CD45RO+, NK cell, and monocyte subsets immediately upon HD procedure. Our result suggested that the timing of IGRA testing is crucial in end-stage renal disease population.