Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 568
Filtrar
1.
Acta Pharmacol Sin ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758356

RESUMO

Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in clinic. The activation of NLRP3 inflammasome is associated with inflammation and renal injury in I/R-induced AKI. In the current study we explored the molecular and cellular mechanisms for NLRP3 inflammasome activation following renal I/R. Mice were subjected to I/R renal injury by clamping bilateral renal pedicles. We showed that I/R injury markedly increased caspase-11 expression and the cleavage of pannexin 1 (panx1) in the kidneys accompanied by NLRP3 inflammasome activation evidenced by the activation of caspase-1 and interlukin-1ß (IL-1ß) maturation. In Casp-11-/- mice, I/R-induced panx1 cleavage, NLRP3 inflammasome activation as well as renal functional deterioration and tubular morphological changes were significantly attenuated. In cultured primary tubular cells (PTCs) and NRK-52E cells, hypoxia/reoxygenation (H/R) markedly increased caspase-11 expression, NLRP3 inflammasome activation, IL-1ß maturation and panx1 cleavage. Knockdown of caspase-11 attenuated all those changes; similar effects were observed in PTCs isolated from Casp-11-/- mice. In NRK-52E cells, overexpression of caspase-11 promoted panx1 cleavage; pretreatment with panx1 inhibitor carbenoxolone or knockdown of panx1 significantly attenuated H/R-induced intracellular ATP reduction, extracellular ATP elevation and NLRP3 inflammasome activation without apparent influence on H/R-induced caspase-11 increase; pretreatment with P2X7 receptor inhibitor AZD9056 also attenuated NLRP3 inflammasome activation. The above results demonstrate that the cleavage of panx1 by upregulated caspase-11 is involved in facilitating ATP release and then NLRP3 inflammasome activation in I/R-induced AKI. This study provides new insight into the molecular mechanism of NLRP3 inflammasome activation in AKI.

2.
Sci Total Environ ; 778: 146288, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33714834

RESUMO

Fine particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) poses adverse impacts on public health and the environment. It is still a great challenge to estimate high-resolution PM2.5 concentrations at moderate scales. The current study calibrated PM2.5 concentrations at a 1 km resolution scale using ground-level monitoring data, Aerosol Optical Depth (AOD), meteorological data, and auxiliary data via Random Forest (RF) model across China in 2017. The three ten-folded cross-validations (CV) methods including sample-based, time-based, and spatial-based validation combined with Coefficient Square (R2), Root-Mean-Square Error (RMSE), and Mean Predictive Error (MPE) have been used for validation at different temporal scales in terms of daily, monthly, heating seasonal, and non-heating seasonal. Finally, the distribution map of PM2.5 concentrations was illustrated based on the RF model. Some findings were achieved. The RF model performed well, with a relatively high sample-based cross-validation R2 of 0.74, a low RMSE of 16.29 µg × m-3, and a small MPE of -0.282 µg × m-3. Meanwhile, the performance of the RF model in inferring the PM2.5 concentrations was well at urban scales except for Chengyu (CY). North China, the CY urban agglomeration, and the northwest of China exhibited relatively high PM2.5 pollution features, especially in the heating season. The robustness of the RF model in the present study outperformed most statistical regression models for calibrating PM2.5 concentrations. The outcomes can supply an up-to-date scientific dataset for epidemiological and air pollutants exposure risk studies across China.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33729030

RESUMO

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in ARDS patients compared to healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control (GGPPSfl/fl) and myeloid-selective knockout (GGPPSfl/flLysMcre) mice were then generated. Interestingly, using a LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency up-regulated the production of LPS-induced IL-6, IL-1ß, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33693494

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor in Chinese subjects with hyperuricemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid levels ≥480 µmol/l with gout, or sUA levels ≥480 µmol/l without gout but with comorbidities, or sUA levels ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg/5 mg/10 mg of SHR4640, 50 mg of benzbromarone, and placebo, respectively. The primary end point was the proportion of subjects achieved target sUA level of ≤ 360 µmol/l at week 5. RESULTS: About 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in 5 mg, 10 mg of SHR4640 and benzbromarone groups, respectively, significantly higher than placebo group (0%; p< 0.05 for 5 mg and 10 mg of SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg of SHR4640 and benzbromarone, respectively, vs placebo (5.9%; p< 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect, and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as comparing with placebo in Chinese subjects with hyperuricemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33674974

RESUMO

The COVID-19 is still a huge challenge that seriously threatens public health globally. Previous studies focused on the influence of air pollutants and probable meteorological parameters on confirmed COVID-19 infections via epidemiological methods, whereas the findings of relations between possible variables and COVID-19 incidences using geographical perspective were scarce. In the present study, data concerning confirmed COVID-19 cases and possible affecting factors were collected for 325 cities across China up to May 27, 2020. The geographically weighted regression (GWR) model was introduced to explore the impact of probable determinants on confirmed COVID-19 incidences. Some results were obtained. AQI, PM2.5, and PM10 demonstrated significantly positive impacts on COVID-19 during the most study period with the majority lag group (P< 0.05). Nevertheless, the relation of temperature with COVID-19 was significantly negative (P< 0.05). Especially, CO exhibited a negative effect on COVID-19 in most study period with the majority lag group. The impacts of each possible determinant on COVID-19 represented significantly spatial heterogeneity. The obvious influence of the majority of possible factors on COVID-19 was mainly detected during the after lockdown period with the lag 21 group. Although the COVID-19 spreading has been effectively controlled by tough measures taken by the Chinese government, the study findings remind us to address the air pollution issues persistently for protecting human health.

6.
Front Endocrinol (Lausanne) ; 12: 629831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716980

RESUMO

Background: Iron deficiency (ID) is concerned as the most common nutritional deficiency worldwide. The effects of ID on thyroid function and autoimmunity in pregnant women and reproductive-age women are controversial. The aim of the current study was to summarize the evidences and evaluate the relationship between ID and thyroid disorders. Methods: In this systematic review and meta-analysis, studies published on the Cochrane, Embase, Medline, and PubMed databases by October 2020 were searched. A total of 636 studies which discussed the correlation between ID and thyroid disorders were eligible in the initial search. Pooled mean differences (MD) and 95% confidence intervals (CI) were calculated for the assessment of thyrotropin (TSH) and free thyroxine (FT4) levels. Combined odd ratios (OR) and 95% CI were calculated for the assessment of the prevalence of overt and subclinical hypothyroidism, positive thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). Results: For women of reproductive age, ID could significantly increase the risk of positive TPOAb (OR: 1.89; 95% CI: 1.17, 3.06: P = 0.01) and both positive TPOAb and TgAb (OR: 1.48; 95% CI: 1.03, 2.11: P = 0.03). The meta-analysis of pregnant women showed that pregnant women with ID had increased serum TSH levels (MD: 0.12; 95% CI: 0.07, 0.17; P < 0.00001) and decreased FT4 levels (MD: -0.73; 95% CI: -1.04, -0.41; P < 0.00001). Meanwhile, the prevalence of overt (OR: 1.60; 95% CI: 1.17, 2.19; P = 0.004) and subclinical (OR: 1.37; 95% CI: 1.13, 1.66; P = 0.001) hypothyroidism in pregnant women with ID was significantly increased. Conclusions: ID may adversely affect thyroid function and autoimmunity of pregnant and reproductive-age women and it is very necessary for monitoring iron nutritional status and early treatment of ID for them.

7.
ACS Sens ; 6(3): 881-888, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33645226

RESUMO

Coronavirus Disease 2019 (COVID-19), which is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has rapidly spread leading to a global pandemic. Here, we combined multiple cross displacement amplification (MCDA) with CRISPR-Cas12a-based detection to develop a novel diagnostic test (MCCD) and applied for the diagnosis of COVID-19, called COVID-19 MCCD. The MCCD protocol conducts reverse transcription MCDA (RT-MCDA) reaction for RNA templates followed by CRISPR-Cas12a/CrRNA complex detection of predefined target sequences after which degradation of a single-strand DNA (ssDNA) molecule confirms detection of the target sequence. Two MCDA primer sets and two CrRNAs were designed targeting the opening reading frame 1a/b (ORF1ab) and nucleoprotein (N) of SARS-CoV-2. The optimal conditions include two RT-MCDA reactions at 63 °C for 35 min and a CRISPR-Cas12a/CrRNA detection reaction at 37 °C for 5 min. The COVID-19 MCCD assay can be visualized on a lateral flow biosensor (LFB) and completed within 1 h including RNA extraction (15 min), RT-MCDA reaction (35 min), CRISPR-Cas12a/CrRNA detection reaction (5 min), and reporting of result (within 2 min). The COVID-19 MCCD assay is very sensitive and detects the target gene with as low as seven copies per test and does not cross-react with non-SARS-CoV-2 templates. SARS-CoV-2 was detected in 37 of 37 COVID-19 patient samples, and nonpositive results were detected from 77 non-COVID-19 patients. Therefore, the COVID-19 MCCD assay is a useful tool for the reliable and quick diagnosis of SARS-CoV-2 infection.


Assuntos
Proteínas de Bactérias , Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Endodesoxirribonucleases , Técnicas de Amplificação de Ácido Nucleico , RNA Viral , /genética , Técnicas Biossensoriais , Humanos , Sensibilidade e Especificidade
8.
Sci Adv ; 7(5)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33571129

RESUMO

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

9.
Environ Toxicol ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33547861

RESUMO

Nickel oxide nanoparticles (NiO NPs) causes pulmonary fibrosis via activating transforming growth factor-ß1 (TGF-ß1) in rats, but its upstream regulatory mechanisms are unknown. This study aimed to explore the role of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in NiO NPs-induced collagen deposition. Male Wistar rats were intratracheally instilled with NiO NPs (0.015, 0.06, and 0.24 mg/kg b.w.) twice a week for 9 weeks. Human lung adenocarcinoma epithelial cells (A549 cells) were cultured with NiO NPs (25, 50, and 100 µg/ml) to establish collagen deposition model. We discovered that NiO NPs-induced rat pulmonary fibrosis was accompanied by the epithelial-mesenchymal transition (EMT) occurrence and MEG3 down-regulation in rat lung tissues. In cell collagen deposition model, NiO NPs also evoked EMT and decreased MEG3 expression in a dose-dependent manner in A549 cells. By overexpressing MEG3 in A549 cells, we found that MEG3 inhibited the level of TGF-ß1, EMT process and collagen formation. Moreover, our data showed that SB431542 (TGF-ß1 inhibitor) had an inhibitory effect on NiO NPs-induced EMT and collagen formation. Our results indicated that MEG3 inhibited NiO NPs-induced collagen deposition by regulating TGF-ß1-mediated EMT process, which may provide some clues for insighting into the mechanisms of NiO NPs-induced pulmonary fibrosis.

10.
Nano Lett ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596656

RESUMO

Efficient endosomal escape is the most essential but challenging issue for siRNA drug development. Herein, a series of quaternary ammonium-based amphiphilic triblock polymers harnessing an elaborately tailored pH-sensitive hydrophobic core were synthesized and screened. Upon incubating in an endosomal pH environment (pH 6.5-6.8), mPEG45-P(DPA50-co-DMAEMA56)-PT53 (PDDT, the optimized polymer) nanomicelles (PDDT-Ms) and PDDT-Ms/siRNA polyplexes rapidly disassembled, leading to promoted cytosolic release of internalized siRNA and enhanced silencing activity evident from comprehensive analysis of the colocalization and gene silencing using a lysosomotropic agent (chloroquine) and an endosomal trafficking inhibitor (bafilomycin A1). In addition, PDDT-Ms/siPLK1 dramatically repressed tumor growth in both HepG2-xenograft and highly malignant patient-derived xenograft models. PDDT-Ms-armed siPD-L1 efficiently blocked the interaction of PD-L1 and PD-1 and restored immunological surveillance in CT-26-xenograft murine model. PDDT-Ms/siRNA exhibited ideal safety profiles in these assays. This study provides guidelines for rational design and optimization of block polymers for efficient endosomal escape of internalized siRNA and cancer therapy.

11.
Adv Exp Med Biol ; 1278: 81-94, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523444

RESUMO

Metabolic programs and dynamic nutrient signaling can direct cell biological function. Cellular metabolism and biological function are coordinated to cell activity. Regulatory T cells (Foxp3+ Tregs) expressing the key transcription factor FOXP3 play critical roles in the maintenance of immune tolerance and in the control of immune homeostasis. A bundle of data demonstrated that Foxp3+ Tregs were influenced and regulated by Toll-cell receptor (TCR) and costimulatory signals, cytokine conditions and metabolic changes, including metabolites, etc. In this context, Foxp3+ Tregs are impacted by different environmental conditions and metabolic differences associated with diverse transcriptional patterns, which, in turn, display a high degree of plasticity and tissue specificity. During the past decades, significant progresses have been made in understanding the correlation between metabolic changes and manipulation of Foxp3+ Treg function. Taken together, this chapter aims to summarize the important advances in the fields, decipher what metabolic ways are involved in Foxp3+ Tregs, and how metabolism modulates Foxp3 expression, stability, and suppressive functions, which may provide a potential pace on lightening up Foxp3+ Treg-mediated immune functions.


Assuntos
Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Homeostase , Tolerância Imunológica , Transdução de Sinais , Linfócitos T Reguladores/metabolismo
12.
Am J Orthod Dentofacial Orthop ; 159(3): 312-320, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33526298

RESUMO

INTRODUCTION: This study investigated the prevalence of and risk factors for alveolar fenestration and dehiscence in the anterior teeth of Chinese patients with skeletal Class III malocclusion. METHODS: This study included clinical and radiographic examinations and intraoperative observations of 460 anterior teeth from 54 patients who underwent corticotomy and periodontal regenerative surgery before orthodontic treatment. Fenestration and dehiscence were detected and recorded during open-flap surgery. Univariate and multivariate analyses were performed to assess relationships between fenestration and dehiscence and age, sex, history of previous orthodontic treatment, mandibular plane angle, dentition, tooth position, sagittal root position, periodontal biotype, gingival recession, width of keratinized gingiva, and width of the basal bone. RESULTS: The prevalence of buccal alveolar bone defects was 16.1% (fenestration) and 20.7% (dehiscence) at the tooth level. Multivariate logistic regressions showed that fenestration was significantly associated with tooth position (canine vs central incisor, odds ratio [OR] = 3.324; P = 0.006; lateral incisor vs central incisor, OR = 5.588; P  <0.001), and sagittal root position (buccally positioned vs centrally positioned, OR = 5.865; P = 0.025). Dehiscence was significantly associated with dentition (mandible vs maxilla, OR = 11.685; P  <0.001), tooth position (canine vs central incisor, OR = 3.863; P = 0.007), age (OR = 1.227; P = 0.010), sex (male vs female, OR = 5.530; P = 0.026), and history of orthodontic treatment (yes vs no, OR = 4.773; P = 0.028). CONCLUSIONS: Buccally positioned teeth in the osseous housing, lateral incisors, and canines were more likely to exhibit alveolar fenestration. Mandibular teeth and canines, patients who were older, were male, and had a history of orthodontic treatment, were more likely to exhibit alveolar dehiscence.


Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , China/epidemiologia , Feminino , Humanos , Masculino , Mandíbula , Prevalência , Fatores de Risco
13.
Korean J Radiol ; 22(4): 502-512, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33569928

RESUMO

OBJECTIVE: To objectively and subjectively assess and compare the characteristics of monoenergetic images [MEI (+)] and polyenergetic images (PEI) acquired by dual-energy CT (DECT) of patients with breast cancer. MATERIALS AND METHODS: This retrospective study evaluated the images and data of 42 patients with breast cancer who had undergone dual-phase contrast-enhanced DECT from June to September 2019. One standard PEI, five MEI (+) in 10-kiloelectron volt (keV) intervals (range, 40-80 keV), iodine density (ID) maps, iodine overlay images, and Z effective (Zeff) maps were reconstructed. The contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) were calculated. Multiple quantitative parameters of the malignant breast lesions were compared between the arterial and the venous phase images. Two readers independently assessed lesion conspicuity and performed a morphology analysis. RESULTS: Low keV MEI (+) at 40-50 keV showed increased CNR and SNRbreast lesion compared with PEI, especially in the venous phase ([CNR: 40 keV, 20.10; 50 keV, 14.45; vs. PEI, 7.27; p < 0.001], [SNRbreast lesion: 40 keV, 21.01; 50 keV, 16.28; vs. PEI, 10.77; p < 0.001]). Multiple quantitative DECT parameters of malignant breast lesions were higher in the venous phase images than in the arterial phase images (p < 0.001). MEI (+) at 40 keV, ID, and Zeff reconstructions yielded the highest Likert scores for lesion conspicuity. The conspicuity of the mass margin and the visual enhancement were significantly better in 40-keV MEI (+) than in the PEI (p = 0.022, p = 0.033, respectively). CONCLUSION: Compared with PEI, MEI (+) reconstructions at low keV in the venous phase acquired by DECT improved the objective and subjective assessment of lesion conspicuity in patients with malignant breast lesions. MEI (+) reconstruction acquired by DECT may be helpful for the preoperative evaluation of breast cancer.

14.
Cancer Imaging ; 21(1): 4, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413654

RESUMO

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 are the most useful immunohistochemical biomarkers of invasive breast cancer. The purpose of this study is to investigate the possibility of quantitative parameters derived from dual-energy CT (DECT) to discriminate immunohistochemical biomarkers of invasive breast cancer. METHODS: This prospective study enrolled 120 patients with invasive breast cancer who underwent preoperative contrast-enhanced DECT for staging purposes from June 2019 to January 2020. DECT quantitative parameters, including normalized iodine concentration (NIC), the slope of the spectral Hounsfield unit curve (λHu), and the normalized effective atomic number (nZeff), were obtained from reconstructed images. DECT quantitative parameters were compared with the expression status, and the correlations with the value of immunohistochemical biomarkers were evaluated. Inter-observer reproducibility analysis was performed to assess the measurement reproducibility of quantitative parameters. The diagnostic performance of the quantitative parameters was analyzed by receiver operating characteristic curve. RESULTS: The ER-negative group tended to display higher venous phase NIC and nZeff compared with the ER-positive group (individually, p = 0.003, 0.011; area under the curve [AUC] of 0.65, 0.60). The PR-negative group demonstrated higher arterial and venous phase NIC compared with the PR-positive group (individually, p = 0.022, 0.005; AUC of 0.63, 0.65). NIC was correlated negatively with the value of ER and PR expression (r = - 0.175 ~ - 0.265, p = 0.002 ~ 0.042). The HER2-positive group tended to display higher venous phase nZeff than the HER2-negative group (p = 0.022; AUC of 0.59). The Ki67 high-proliferation group demonstrated higher arterial phase, venous phase NIC and nZeff than the Ki67 low-proliferation group (p < 0.001 ~ 0.005; AUC of 0.67 ~ 0.75). Both the NIC and nZeff were correlated positively with the value of Ki67 (r = 0.240 ~ 0.490, p < 0.001 ~ 0.014). CONCLUSIONS: NIC and nZeff derived from DECT could be used to discriminate expression status and may associate with the value of immunohistochemical biomarkers of invasive breast cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico por imagem , Antígeno Ki-67/análise , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Iodo , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Reprodutibilidade dos Testes
15.
Sci Total Environ ; 768: 144446, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33434806

RESUMO

In this study, by inoculating nitritation suspended sludge, simultaneous nitritation, anammox and denitrification (SNAD) was established quickly in an integrated fixed-biofilm activated sludge (IFAS) reactor to treat high-ammonia municipal wastewater. Results showed that, deep-level total nitrogen and chemical oxygen demand removal efficiencies (92.8% and 78.8%, respectively) were achieved, and their effluent concentrations were 13.2 and 39.3 mg/L, respectively. Excess generation of nitrate was once occurred under continuous aerobic condition, but it could be solved by suppressing nitrite oxidizing bacteria activity stably via switching to intermittent aeration mode (alternate 7 min of aerobic and 21 min of anoxic) and rising influent ammonium concentration temporarily (lasted 31 days). High-throughput sequencing analysis revealed that, Candidatus_Brocadia, as dominant anammox bacteria, was self-generated in flocs (2.93%) but mainly biofilm (7.67%), whereas uncultured_f_Nitrosomonadaceae as ammonia oxidizing bacteria was mainly found in flocs (2.4%). This work not only demonstrated that anammox bacteria could be self-generated and retained in the SNAD-IFAS system, but also suggested a promising application of the SNAD-IFAS in wastewater treatment plants.


Assuntos
Compostos de Amônio , Esgotos , Bactérias , Biofilmes , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Águas Residuárias
16.
J Cell Mol Med ; 25(4): 1958-1971, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33434361

RESUMO

The activation of Wnt/ß-catenin pathway plays a pivotal role in promoting renal fibrosis. The activation of Wnt/ß-catenin pathway relies on the binding of Wnts to Frizzled receptors on cell membrane. However, the factor regulating Wnts production remains unclear. Here, we demonstrated that transcriptional factor FoxM1 was significantly increased in obstructed kidneys and patients' kidneys with fibrosis. The up-regulation of FoxM1 mainly distributed in tubular epithelial cells. Pharmacological inhibition of FoxM1 down-regulated multi-Wnts elevation in UUO mice and attenuated renal fibrosis. In cultured renal tubular epithelial cells, overexpression of FoxM1 promoted 8 Wnts expression, while knock-down on FoxM1-suppressed multi-Wnts including Wnt1, Wnt2b and Wnt3 expression induced by Ang II. Chromatin immunoprecipitation PCR confirmed that FoxM1 bound to Wnt1, Wnt2b, Wnt3 promoters and luciferase assay further identified that the transcriptions of Wnt1, Wnt2b and Wnt3 were regulated by FoxM1. Thus, our findings show that multi-Wnt family members were regulated by transcriptional factor FoxM1. FoxM1 might be a key switch for activating ß-catenin pathway and renal fibrosis. Therefore, FoxM1 might be a potential therapeutic target in manipulating renal fibrosis.

17.
ACS Appl Mater Interfaces ; 13(2): 2218-2229, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33406826

RESUMO

pH-sensitive hydrophobic segments have been certificated to facilitate siRNA delivery efficiency of amphiphilic polycation vehicles. However, optimal design concepts for these vehicles remain unclear. Herein, by studying the library of amphiphilic polycations mPEG-PAMA50-P(DEAx-r-D5Ay) (EAE5x/y), we concluded a multifactor matching concept (pKa values, "proton buffering capacities" (BCs), and critical micelle concentrations (CMCs)) for polycation vehicles to improve siRNA delivery efficiency in vitro and in vivo. We identified that the stronger BCs in a pH 5.5-7.4 subset induced by EAE548/29 (pKa = 6.79) and EAE539/37 (pKa = 6.20) are effective for siRNA delivery in vitro. Further, the stronger BCs occurred in a narrow subset of pH 5.5-6.5 and the lower CMC attributed to higher siRNA delivery capacity of EAE539/37 in vivo than EAE548/29 after intravenous administration and subcutaneous injection. More importantly, 87.2% gene knockdown efficacy was achieved by EAE539/37 via subcutaneous injection, which might be useful for an mRNA vaccine adjuvant. Furthermore, EAE539/37 also successfully delivered siRRM2 to tumor via intravenous administration and received highly efficient antitumor activity. Taken together, the suitable pKa values, strong BCs occurred in pH 5.5-6.5, and low CMCs were probably the potential solution for designing efficient polycationic vehicles for siRNA delivery.


Assuntos
Polieletrólitos/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , RNA Interferente Pequeno/genética
18.
Virol J ; 18(1): 27, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499896

RESUMO

BACKGROUND: Orf virus (ORFV) is a member of the genus Parapoxvirus and family Poxviridae. The virus has a worldwide distribution and infects sheep, goats, humans, and wild animals. However, due to the complex structure of the poxvirus, the underlying mechanism of the entry and infection by ORFV remains largely unknown. ORFV ORF047 encodes a protein named L1R. Poxviral L1R serves as the receptor-binding protein and blocks virus binding and entry independently of glycosaminoglycans (GAGs). The study aimed to identify the host interaction partners of ORFV ORF047. METHODS: Yeast two-hybrid cDNA library of sheep testicular cells was applied to screen the host targets with ORF047 as the bait. ORF047 was cloned into a pBT3-N vector and expressed in the NMY51 yeast strain. Then, the expression of bait proteins was validated by Western blot analysis. RESULTS: Sheep SERP1and PABPC4 were identified as host target proteins of ORFV ORF047, and a Co-IP assay further verified their interaction. CONCLUSIONS: New host cell proteins SERP1and PABPC4 were found to interact with ORFV ORF047 and might involve viral mRNA translation and replication.

19.
Nat Prod Bioprospect ; 11(1): 137-142, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33411321

RESUMO

Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives, setosphlides A-D (1-4), and four known analogues (5-8). Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods. The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra. The C-10 relative configurations for the pair of C-10 epimers (1 and 2) were established by comparing the magnitude of the computed 13C NMR chemical shifts (Δδcalcd.) with the experimental 13C NMR values (Δδexp.) for the epimers. All of the isolated compounds (1-8) were evaluated for their cytotoxicities against four human tumor cell lines MCF-7, MGC-803, HeLa, and Huh-7.

20.
Bioresour Technol ; 319: 124164, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33002785

RESUMO

For achieving mainstream anaerobic ammonium oxidation (Anammox), there is a need to achieve organic carbon and phosphorus removal meanwhile supplying nitrite (NO2--N). Based on this demand, a novel anaerobic/anoxic/aerobic operated denitrifying nitrite accumulation and phosphorus removal (DNAPR) process was proposed for treating synthetic municipal and nitrate (NO3--N) wastewaters simultaneously (volume ratio of 5:1). By adjusting influent composition, discharging anaerobic-end supernatant, shortening anoxic duration, and adding a short aerobic stage, DNAPR process achieved promising and stable nitrate-to-nitrite transformation (78.35%) and phosphorus removal (98.34%) performance. Moreover, effluent with chemical oxygen demand of 16.63 mg/L, nitrite of 54.16 mg/L, orthophosphate of 0.37 mg/L, and nitrite to ammonia ratio of 1.3 were finally obtained after 141-day operation. Microbiological analysis showed that Thauera (34.9%) and unclassified_f_Rhodobacteraceae (6.79%) were both responsible for DNAPR. Therefore, DNAPR, serving as promising alternative pretreatment, might possess significance for achieving mainstream Anammox.


Assuntos
Nitritos , Fósforo , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Esgotos , Águas Residuárias
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...