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2.
Exp Mol Med ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990690

RESUMO

STAT5 is a transcription factor that is activated by various cytokines, hormones, and growth factors. Activated STAT5 is then translocated to the nucleus and regulates the transcription of target genes, affecting several biological processes. Several studies have investigated the role of STAT5 in adipogenesis, but unfortunately, its role in adipogenesis remains controversial. In the present study, we generated adipocyte-specific Stat5 conditional knockout (cKO) (Stat5fl/fl;Apn-cre) mice to investigate the role of STAT5 in the adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSC adipogenesis was significantly inhibited upon overexpression of constitutively active STAT5A, while it was enhanced in the absence of Stat5 in vitro. In vivo adipose staining and histological analyses revealed increased adipose volume in the bone marrow of Stat5 cKO mice. ATF3 is the target of STAT5 during STAT5-mediated inhibition of adipogenesis, and its transcription is regulated by the binding of STAT5 to the Atf3 promoter. ATF3 overexpression was sufficient to suppress the enhanced adipogenesis of Stat5-deficient adipocytes, and Atf3 silencing abolished the STAT5-mediated inhibition of adipogenesis. Stat5 cKO mice exhibited reduced bone volume due to an increase in the osteoclast number, and coculture of bone marrow-derived macrophages with Stat5 cKO adipocytes resulted in enhanced osteoclastogenesis, suggesting that an increase in the adipocyte number may contribute to bone loss. In summary, this study shows that STAT5 is a negative regulator of BMSC adipogenesis and contributes to bone homeostasis via direct and indirect regulation of osteoclast differentiation; therefore, it may be a leading target for the treatment of both obesity and bone loss-related diseases.

3.
Parasite Immunol ; : e12868, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991355

RESUMO

AIMS: We investigated whether tryptase released from mast cells activated by prostate stromal cells (PSC) reacted with Trichomonas vaginalis (Tv) promoted the proliferation of PSC through protease- activated receptor 2 (PAR2). METHODS AND RESULTS: Conditioned medium of PSC was prepared by stimulating them with Tv (Trichomonad-conditioned medium (TCM)), and mast cell-conditioned medium were prepared by incubating them with TCM (mast cell-TCM (M-TCM)). Mast cells incubated with TCM migrated more efficiently and produced more ß-hexosaminidase and tryptase. M-TCM containing tryptase increased the proliferation of PSC, while inhibition of tryptase decreased proliferation. Expression of signaling molecules such as PAR2, p-ERK, COX-2, 15d-PGJ2 and PPARγ, known to be involved in the tryptase-PAR2 pathway, increased in response to M-TCM, and blocking any of these signals decreased proliferation, indicating that tryptase-PAR2 signaling is involved in the proliferation of PSC. Inhibition of tryptase and PAR2 led to reduced expression of PAR2, p-ERK, COX-2, 15d-PGJ2 and PPARγ, while inhibition of ERK or COX-2 reduced the expression of COX-2, 15d-PGJ2 and PPARγ indicating that the tryptase-PAR2 pathway proceeds in the order p-ERK, COX-2, 15d-PGJ2 , and PPARγ. CONCLUSION: These results show that interaction between PSC stimulated with Tv and mast cells causes proliferation of PSC through the tryptase-PAR2 pathway.

4.
Mar Pollut Bull ; 168: 112383, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940367

RESUMO

We investigated a sediment core collected from the Geum Estuary through sedimentological and geochemical analyses. Three lithological units were classified based on sedimentological characteristics. Unit 1 and Unit 3 were geochemically distinct, while Unit 2 was the transitional phase between them. The geochemical results suggest that the contribution of terrestrial organic carbon (OC) to the sedimentary OC pool in the coarse-grained Unit 1 was lesser than that of fine-grained Unit 3. The excess activity (210Pbex) and the sedimentation rate indicate that Unit 1 corresponded to 1977 Common Era (CE). Since the first dam construction on the Geum River began in 1975 CE, the deposition of Unit 1 in the Geum Estuary is likely associated with river impoundments, which reduce the delivery of fine-grained sediment and terrestrial OC to the estuary. This study highlights the role of river impoundments in altering the sedimentary OC and thus the sedimentary environment in the estuary.

5.
Chemosphere ; 280: 130419, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33940450

RESUMO

We reviewed washing of radioactive Cs-contaminated concrete and soil based on the fate of Cs in concrete and soil, including sorption materials for treatment of supernatant solution. In non-aged cement materials (the calcium silicate hydration (C-S-H) phase), it was possible to decontaminate Cs using ion exchange with monovalent cations, such as NH4+. The clay components in the soil and aggregates were important factors in optimization of the efficiency and mechanism for Cs decontamination with washing solution. The parameters (reagent component, pH, and temperature) of the washing solution should be determined considering soil mineral type (here, weathered biotite (WB) with vermiculite), since monovalent cations such as NH4+ and K+ can inhibit Cs decontamination due to collapse of the hydrated and expanded interlayer regions with cation exchange. In this case, hydrothermal treatment or H2O2 dosing was necessary to expand the collapsed interlayer region for Cs removal by washing with cation exchange or organic acids. Acid and a chelating agent significantly enhanced Cs-release with dissolution of the adsorbent layer containing iron and aluminum oxides. The important characteristics of important and emerging sorption materials for treatment of the radioactive Cs-contaminated supernatant after washing treatment are discussed. Sorbents for treatment of washing supernatant are divided in to two main categories. Clay minerals, metal hexacyanoferrates, and ammonium molybdophosphates are discussed in the inorganic class of materials. Hypercrosslinked polymers, supramolecular sorbents, carbon nanotubes, and graphene oxide are covered in the carbon-based sorbents for Cs removal from water.

6.
PLoS Genet ; 17(5): e1009516, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33983932

RESUMO

Adenosine deaminase acting on RNA 1 (ADAR1), an enzyme responsible for adenosine-to-inosine RNA editing, is composed of two isoforms: nuclear p110 and cytoplasmic p150. Deletion of Adar1 or Adar1 p150 genes in mice results in embryonic lethality with overexpression of interferon-stimulating genes (ISGs), caused by the aberrant recognition of unedited endogenous transcripts by melanoma differentiation-associated protein 5 (MDA5). However, among numerous RNA editing sites, how many RNA sites require editing, especially by ADAR1 p150, to avoid MDA5 activation and whether ADAR1 p110 contributes to this function remains elusive. In particular, ADAR1 p110 is abundant in the mouse brain where a subtle amount of ADAR1 p150 is expressed, whereas ADAR1 mutations cause Aicardi-Goutières syndrome, in which the brain is one of the most affected organs accompanied by the elevated expression of ISGs. Therefore, understanding RNA editing-mediated prevention of MDA5 activation in the brain is especially important. Here, we established Adar1 p110-specific knockout mice, in which the upregulated expression of ISGs was not observed. This result suggests that ADAR1 p150-mediated RNA editing is enough to suppress MDA5 activation. Therefore, we further created Adar1 p110/Adar2 double knockout mice to identify ADAR1 p150-mediated editing sites. This analysis demonstrated that although the elevated expression of ISGs was not observed, only less than 2% of editing sites were preserved in the brains of Adar1 p110/Adar2 double knockout mice. Of note, we found that some sites were highly edited, which was comparable to those found in wild-type mice, indicating the presence of ADAR1 p150-specific sites. These data suggest that RNA editing at a very limited sites, which is mediated by a subtle amount of ADAR1 p150, is sufficient to prevents MDA5 activation, at least in the mouse brain.

7.
Am J Clin Nutr ; 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964853

RESUMO

BACKGROUND: The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits. OBJECTIVES: To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore. METHODS: This is a 16-week, parallel design, randomized controlled trial. All participants (n = 40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid-lipoproteins and blood pressure were evaluated every 4 weeks. RESULTS: All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92 ± 1.73 nmol/mL; control: 5.01 ± 2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19 ± 0.06 pg/mL; control: -0.15 ± 0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08 ± 0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8 ± 0.5%) and vascular age (-1.9 ± 1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes. CONCLUSIONS: In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid-lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844.

8.
PLoS One ; 16(5): e0250616, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939723

RESUMO

PURPOSE: To determine the diagnostic accuracy of the Xpert MTB/RIF assay in patients with smear-negative pulmonary tuberculosis (TB) and to assess clinical and CT characteristics of Xpert-negative pulmonary TB. MATERIAL AND METHODS: We retrospectively reviewed the records of 1,400 patients with suspected pulmonary TB for whom the sputum Xpert MTB/RIF assay was performed between September 1, 2014 and February 28, 2020. Clinical and CT characteristics of smear-negative pulmonary TB patients with negative Xpert MTB/RIF results were compared with positive results. RESULTS: Of 1,400 patients, 365 (26.1%) were diagnosed with pulmonary TB and 190 of 365 patients (52.1%) were negative for sputum acid-fast bacilli. The diagnosis of pulmonary TB was based on a positive culture, positive Xpert MTB/RIF or the clinical diagnoses of patients treated with an anti-TB medication. The sensitivity, specificity, positive predictive and negative predictive values of sputum Xpert MTB/RIF for smear-negative pulmonary TB were 41.1%, 100%, 100%, and 90.1%, respectively. Finally, 172 patients with smear-negative pulmonary TB who underwent chest CT within 2 weeks of diagnosis were included to compare Xpert-positive (n = 66) and Xpert- negative (n = 106) groups. Patients with sputum Xpert-negative TB showed lower positive rates for sputum culture (33.0% vs. 81.8%, p<0.001) and bronchoalveolar lavage culture (53.3% vs. 84.6%, p = 0.042) than in Xpert-positive TB. Time to start TB medication was longer in patients with Xpert-negative TB than in Xpert-positive TB (11.3±16.4 days vs. 5.0±8.7 days, p = 0.001). On chest CT, sputum Xpert-negative TB showed significantly lower frequency of consolidation (21.7% vs. 39.4%, p = 0.012), cavitation (23.6% vs. 37.9%, p = 0.045), more frequent peripheral location (50.9% vs. 21.2 p = 0.001) with lower area of involvement (4.3±4.3 vs. 7.6±6.4, p<0.001). Multivariate analysis revealed peripheral location (odds ratios, 2.565; 95% confidence interval: 1.157-5.687; p = 0.020) and higher total extent of the involved lobe (odds ratios, 0.928; 95% confidence interval: 0.865-0.995; p = 0.037) were significant factors associated with Xpert MTB/RIF-negative TB. Regardless of Xpert positivity, more than 80% of all cases were diagnosed of TB on chest CT by radiologists. CONCLUSION: The detection rate of sputum Xpert MTB/RIF assay was relatively low for smear negative pulmonary TB. Chest CT image interpretation may play an important role in early diagnosis and treatment of Xpert MTB/RIF-negative pulmonary TB.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33963654

RESUMO

Systematic inactivation of nonribosomal peptide synthetase (NRPS) domains and translocation of the thioesterase (TE) domain revealed several unprecedented nonlinear NRPS assembly processes during the biosynthesis of the cyclodepsipeptide WS9326A in Streptomyces sp. SNM55. First, two sets of type ΙΙ TE (TEΙΙ)-like enzymes mediate the shuttling of activated amino acids between two sets of stand-alone adenylation (A)-thiolation (T) didomain modules and an 'A-less' condensation (C)-T module with distinctive specificities and flexibilities. This was confirmed by the elucidation of the affinities of the A-T didomains for the TEΙΙs and its structure. Second, the C-T didomain module operates iteratively and independently from other modules in the same protein to catalyze two chain elongation cycles. Third, this biosynthetic pathway includes the first example of module skipping, where the interpolated C and T domains are required for chain transfer. Understanding such untapped nonlinear biosynthetic strategies will provide potentially valuable tools for engineered biosynthesis of these complex natural products.

10.
Thyroid ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947272

RESUMO

BACKGROUND: The actions of thyrotropin-binding inhibitory immunoglobulins (TBIIs) against thyrotropin receptors in thyroid follicular cells have been studied as important etiological factors in Graves' disease (GD). The purpose of this study was to investigate changes in the TBII levels of patients undergoing total thyroidectomy (TTx) or radioactive iodine (RAI) therapy for GD refractory to antithyroid drugs (ATD). METHODS: We enrolled patients who underwent TTx or RAI for GD with previous ATD use between January 2011 and December 2017 at the Samsung Seoul Hospital in Seoul, Korea. Thorough retrospective reviews of medical records were performed in 130 patients. RESULTS: Patients with goiter, ophthalmopathy, high levels of TBIIs, and high doses of ATDs received TTx. Elderly patients with arrhythmia received RAI. We observed that TBII levels continued to decrease after TTx. On the other hand, TBIIs initially increased for 138 days (estimated median time) and then decreased slowly after RAI. A faster decline in TBII levels was observed in the TTx group than in the RAI group (p < 0.001). The estimated median time for TBII to decrease below 4.5 IU (3 X upper normal limit, which is known to be a risk factor for fetal hyperthyroidism) was 318 days in the TTx group and 659 days in the RAI group, respectively. With RAI, the numbers of patients at risk of high level TBII (>4.5 IU/L) were 70 (82%) at 6 months, 57 (67%) at 1 year, and 3 (3%) at 2 years. In the TTx group, rapid decreases in TBII levels were observed when the patient was young and the baseline TBII levels were low. In the RAI group, smaller thyroid volume was correlated with more rapid decrease in TBII level. CONCLUSIONS: The changes in TBII levels following TTx or RAI were different in patients with refractory GD. This difference should be considered when TTx or RAI is considered together with patient age, severity of hyperthyroidism, goiter, ophthalmopathy, and future pregnancy plans (for young female patients). .

11.
Langmuir ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33956457

RESUMO

Icephobic surfaces have gained immense attention owing to their significant roles in decreasing the energy consumption of refrigerators and in improving safety issues by preventing the formation of ice on them. Superhydrophobic surfaces incorporating micro- or nanoscale roughness and hydrophobic functional groups have been shown to prevent ice accumulation. Herein, we report a simple, low-cost, and solution-based one-step process for the production of superhydrophobic surfaces with three-dimensional (3D) self-assembled structures. The controlled hydrolysis and polycondensation of n-octadecyltrichlorosilane (OTS-Cl) in an acetone solution produced a highly uniform superhydrophobic surface on various substrates such as glass, metals, and polymers without the limitation of the surface curvature structure. The as-prepared 3D self-assembled surface exhibited a very high contact angle of 161.7° and a low contact hysteresis of 1.47°. The solvent type, H2O content in acetone, and carbon chain length of the silane compound were critical in the formation of self-assembled nanostructures. The thickness of the superhydrophobic 3D self-assembled structure could be varied by controlling the surface properties of the glass substrate. In addition, a novel octadecyl silica nanosquare plate structure was formed as an intermediate for the microlamella structure. The water drop impact experiments on the 3D self-assembled superhydrophobic glass substrates at low temperatures (T < -25 °C) showed that the as-prepared superhydrophobic glass possessed a high impalement threshold for water contact, resulting in excellent and stable icephobic properties. The preparation method proposed in this study is scalable and can be used on a flat glass surface or in a glass vial inside a glass tube. Moreover, it can be applied to various substrates such as metals and polyurethane surfaces with curvature. Therefore, the solution-based self-assembly method proposed in this study is a promising approach to produce superhydrophobic and icephobic surfaces on a wide range of substrates regardless of their structure and properties.

12.
Angiology ; : 33197211012537, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960211

RESUMO

The 2-year clinical outcomes according to pre-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade and reperfusion timing were investigated in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who received newer-generation drug-eluting stents. A total of 7506 NSTEMI patients were divided into 2 groups: early (PCI ≤ 24 hours: n = 6398; pre-PCI TIMI 0/1 [n = 2729], pre-PCI TIMI 2/3 [n = 3669]) and delayed (PCI > 24 hours: n = 1108; pre-PCI TIMI 0/1 [n = 428], pre-PCI TIMI 2/3 [n = 680]) invasive groups. Major adverse cardiac events were defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. All-cause death (P = 0.005 and 0.009, respectively) and cardiac death (P = .003 and 0.046, respectively) were significantly higher in pre-PCI TIMI 0/1 patients than in pre-PCI TIMI 2/3 patients both in the early and delayed invasive groups. In pre-PCI TIMI 0/1 patients, all-cause death rate was significantly higher in the delayed group (P = .023). In pre-PCI TIMI 2/3 patients, the clinical end point was similar between the 2 groups. An early invasive strategy is preferred to a delayed invasive strategy in reducing all-cause death in patients with pre-PCI TIMI 0/1. However, in patients with pre-PCI TIMI 2/3, both treatment strategies are acceptable.

13.
Sci Rep ; 11(1): 9364, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931673

RESUMO

We investigated the effects of stent generation on 2-year clinical outcomes between prediabetes and diabetes patients after acute myocardial infarction (AMI). A total of 13,895 AMI patients were classified into normoglycemia (group A: 3673), prediabetes (group B: 5205), and diabetes (group C: 5017). Thereafter, all three groups were further divided into first-generation (1G)-drug-eluting stent (DES) and second-generation (2G)-DES groups. Patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcome. Stent thrombosis (ST) was the secondary outcome. In both prediabetes and diabetes groups, the cumulative incidences of POCOs, any repeat revascularization, and ST were higher in the 1G-DES than that in the 2G-DES. In the diabetes group, all-cause death and cardiac death rates were higher in the 1G-DES than that in the 2G-DES. In both stent generations, the cumulative incidence of POCOs was similar between the prediabetes and diabetes groups. However, in the 2G-DES group, the cumulative incidences of Re-MI and all-cause death or MI were significantly higher in the diabetes group than that in the prediabetes group. To conclude, 2G-DES was more effective than 1G-DES in reducing the primary and secondary outcomes for both prediabetes and diabetes groups.

14.
Cancer Res Treat ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33940787

RESUMO

Purpose: Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues. Materials and Methods: We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes. Results: Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content. Conclusion: Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.

15.
Nutr Rev ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942088

RESUMO

CONTEXT: L-tryptophan (Trp) has been documented to aid sleep, but a systematic compilation of its effect on sleep quality is still limited. OBJECTIVE: We assessed the effect of Trp supplementation on sleep quality via meta-analysis and meta-regression. The effects of daily Trp dose (<1 g and ≥1 g) were also assessed. DATA SOURCES: A database search was done in PubMed, Medline (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane and a total of 18 articles were collected. DATA EXTRACTION: Extracted data from 4 articles were also analyzed using random-effect meta-analysis and meta-regression. Standardized mean difference (SMD) was used in meta-analysis. DATA ANALYSIS: Results from the study suggested that Trp supplementation can shorten wake after sleep onset (-81.03 min/g, P = 0.017; SMD, -1.08 min [95%CI, -1.89 to -0.28]). In addition, the group receiving ≥1 g Trp supplementation had a shorter wake after sleep onset than the group with Trp < 1g supplementation (Trp <1 g vs Trp ≥1 g: 56.55 vs 28.91 min; P = 0.001). However, Trp supplementation did not affect other sleep components. CONCLUSION: Trp supplementation, especially at ≥1 g can help improve sleep quality.

16.
Viruses ; 13(5)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946221

RESUMO

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

17.
J Hazard Mater ; 416: 125787, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33862480

RESUMO

Despite extensive studies, the fundamental understanding of synergistic mechanisms between sonolysis and photocatalysis for the abatement of persistent organic pollutants (POPs) remains uncertain. As different phases formed under ultrasound irradiation, hydrophilic POPs, sulfamethoxazole (SMX, Kow: 0.89), predominantly resides in bulk liquid and is ineffectively degraded by sonolysis (kUS = 3.33 × 10-3 min-1) since <10% of hydroxyl radicals (·OH) formed at the gas-liquid interface of cavitation is diffused into the bulk, whereas the other fraction rapidly recombines into hydrogen peroxide (H2O2). This study provides a proof-of-concept for the mechanism by presenting various analytical results, endorsing the synergistic role of photoexcited electrons in splitting sonolysis-induced H2O2 into ·OH, particularly in the bulk phase. In a sonophotocatalytic system, the hydrophobic POPs such as bisphenol A (BPA) and atrazine (ATZ) were mainly degraded in gas-liquid interface indicated by the low synergistic values correlation compared to SMX [i.e., SMX has a higher synergistic factor, fsyn (3.26) than BPA (1.30) and ATZ (1.35)]. Also, fsyn was found linearly correlated with the contribution factor of photocatalysis to split H2O2. Three times of consecutive kinetics using an effluent of municipal (MP) wastewater spiked by POPs presented >98% POPs and >96% total organic carbon (TOC) removal.

18.
J Infect Chemother ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33888420

RESUMO

OBJECTIVES: Rapid detection of carbapenemase-producing Enterobacterales (CPE) is important to control spread of the resistance. We previously reported that imipenem disks prepared from injectable imipenem-cilastatin could rapidly detect KPC- and NDM-type carbapenemases. In the present study, we evaluated performance of disks of IPM and combined disks of imipenem-tazobactam and imipenem-EDTA, which were prepared from powders of imipenem and inhibitors. METHODS: Isolates of Enterobacterales were recovered from specimens of patients at a tertiary care hospital in Korea during January 2017 and March 2018. Routine CPE detection was performed by the CPE surveillance personnel whereas evaluation of the Disk carbapenemase test (DCT) was performed by the other personnel without knowing the results of surveillance. The DCT was carried out by pressing disks on to colonies and rehydrating in Petri plates and observing color change. RESULTS: The DCT differentiated 688 of 694 (sensitivity 99.1%) carbapenemase-producing isolates in 2.5-20 min: 630 with KPC, 51 with NDM, three with IMP, one with VIM, two with KPC and IMP, and one with NDM and OXA-181. The DCT failed to detect six OXA- 48-like enzyme-producing isolates, but the modified method using 96-well flat-bottom microplates with mineral oil cover detected all 29 OXA-48-like enzyme-producing isolates in 20-120 min. The DCT was negative for all 440 ertapenem-nonsusceptible, carbapenemase gene-negative isolates (specificity 100%). CONCLUSION: The procedure of DCT is simple and can differentiate isolates of Enterobacterales with KPC-, NDM-, IMP- and VIM-type carbapenemases rapidly, and the modified DCT can detect isolates with OXA-48-like enzymes rapidly.

19.
Sci Adv ; 7(15)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827814

RESUMO

Forkhead box protein A1 (FOXA1) is essential for androgen-dependent prostate cancer (PCa) growth. However, how FOXA1 levels are regulated remains elusive and its therapeutic targeting proven challenging. Here, we report FOXA1 as a nonhistone substrate of enhancer of zeste homolog 2 (EZH2), which methylates FOXA1 at lysine-295. This methylation is recognized by WD40 repeat protein BUB3, which subsequently recruits ubiquitin-specific protease 7 (USP7) to remove ubiquitination and enhance FOXA1 protein stability. They functionally converge in regulating cell cycle genes and promoting PCa growth. FOXA1 is a major therapeutic target of the inhibitors of EZH2 methyltransferase activities in PCa. FOXA1-driven PCa growth can be effectively mitigated by EZH2 enzymatic inhibitors, either alone or in combination with USP7 inhibitors. Together, our study reports EZH2-catalyzed methylation as a key mechanism to FOXA1 protein stability, which may be leveraged to enhance therapeutic targeting of PCa using enzymatic EZH2 inhibitors.

20.
Acta Ophthalmol ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33884766

RESUMO

PURPOSE: Acute and chronic hypertension may have different pathophysiological mechanisms in the retina. Here, we compared the retinal nerve fibre layer (RNFL)/ganglion cell-inner plexiform layer (GC-IPL) thickness ratios of patients with 'relieved' severe hypertensive retinopathy (relieved HTNR) and chronic hypertension without retinopathy (chronic HTN) to those of normal controls. METHODS: We performed cross-sectional study. The eyes were divided into the following groups: normal controls (Group A, age ≥50 years; Group D, age <50 years); chronic HTN (Group B, <10 years of HTN; TNHT; Group C, ≥10 years of HTN); and relieved HTNR (previously diagnosed with grade IV HTNR and relieved retinopathy for >1 year; Group E), and the RNFL/GC-IPL thickness ratio was compared among Groups A-C and between Groups D and E. RESULTS: A total of 379 eyes were included in this study. Groups A-E consisted of 145, 59, 63, 60 and 52 eyes, respectively. The RNFL/GC-IPL thickness ratios were 1.161 ± 0.093, 1.158 ± 0.082 and 1.162 ± 0.089 in groups A-C, respectively, and did not showed a statistically difference (p = 0.966). The RNFL/GC-IPL thickness ratio of groups D and E were 1.169 ± 0.080 and 1.221 ± 0.080, respectively, and showed a statistically difference (p = 0.001). CONCLUSIONS: The RNFL/GC-IPL thickness ratios of the chronic HTN group did not show a difference compared with the normal controls. However, relieved HTNR patients showed a higher ratio than the normal controls. Physicians should be aware that acute hypertensive injury could affect the RNFL/GC-IPL thickness ratio.

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