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1.
ACS Nano ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32049490

RESUMO

The cancer cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize its own kind. These cell membranes are often used to coat spherical nanoparticles to enhance nanomedicines' targeting specificity and uptake. A sphere, however, has only a point contact with a surface at any given time. It is shown here that by retaining a flatter morphology of the cracked cell membrane through stiffening with in situ synthesized gold nanomaterials, an increased area of interaction could be maintained and hence improve upon the in vitro and in vivo homotypic targeting capabilities between cancer cell types. This enhancement is especially important in vivo as any nanomedicine with targeting moieties probably has a single pass at interacting with the target cell before subsequent system clearance. Possible future clinical applications may involve the usage of a patient's autologous tumor biopsy tissues, which are very limited in supply, and therefore ensuring that we capitalize on the entire collective surface area of the cancer cell membrane available becomes an important consideration in the design and delivery our cell membrane-derived nanomedicines.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31942725

RESUMO

Growing evidence suggests the crucial role of microRNAs (miRNAs) in regulating basic cell functions, and therefore participating in the pathologic development of diverse human diseases, including cardiac hypertrophy. Herein, we explained that miR-4458 was distinctly stimulated in Ang II-stimulated hypertrophic H9c2 cells. Intriguingly, miR-4458 inhibition led to exacerbated hypertrophic phenotypes in Ang II-treated H9c2 cells. In addition, the compensatory upregulation of miR-4458 in Ang II-treated H9c2 cells was ascribed to its transcriptional enhancement by NRF1, a transcription factor previously identified to be activated in early cardiac hypertrophy. Moreover, we discovered that miR-4458 served as a negative modulator in cardiac hypertrophy by prompting TFAM, a well-recognized myocardial protective protein. TTP, a RBP that always leads to degradation of recognized mRNAs, was predicted to interact with both miR-4458 and TFAM mRNA. Importantly, we verified that miR-4458 facilitated TFAM expression in cardiomyocytes by directly targeting TTP and releasing TTP-destabilized TFAM mRNA. On the whole, these findings demonstrated that NRF1-induced miR-4458 boosted TFAM via targeting TTP to dampen the exacerbation of cardiac hypertrophy, which indicates miR-4458 as a promising biomarker for the cardiac hypertrophy treatment.

5.
Medicine (Baltimore) ; 99(2): e18661, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914053

RESUMO

RATIONALE: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complex interactions between genetic and environmental factors. Recent studies suggest that Vitamin D3 or bumetanide therapy may improve the core symptoms of ASD in some individuals. However, there are no guidelines that provide clinicians with evidence-based treatment regimens for the use of these therapies in ASD. PATIENT CONCERNS: A 30-month-old female was referred to our department because she did not respond when her name was called. DIAGNOSIS: The patient was diagnosed with ASD by a team of autism experts according to American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. INTERVENTIONS: The patient was administered Vitamin D3 150,000 IU intramuscularly once a month and Vitamin D3 800 IU orally each day. After 6 months, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Subsequently, oral bumetanide 0.5 mg twice daily was initiated. OUTCOMES: The patient's symptoms remained unchanged after 6 months of Vitamin D3 supplementation, and her serum 25 (OH) D levels had reached 52.4 ng/mL. At the parent's request, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Thereafter, bumetanide was initiated. After 1 month of bumetanide, the patient's Childhood Autism Rating Scale score was 26, which is below the cutoff score for ASD. This case report suggests that Vitamin D3 and bumetanide target different mechanisms in the pathogenesis of ASD. LESSONS: Based on these observations, we discuss three possible scenarios for Vitamin D3 supplementation and propose that bumetanide should be initiated if Vitamin D3 supplementation is ineffective (identifier ChiCTR-CCC-13004498).


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Bumetanida/uso terapêutico , Vitamina D/uso terapêutico , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos
6.
Adv Sci (Weinh) ; 7(2): 1903603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993298

RESUMO

[This corrects the article DOI: 10.1002/advs.201800981.].

7.
Bioresour Technol ; 301: 122764, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958691

RESUMO

The sucrose metabolic genes (scrA, scrB and scrK) from C. acetobutylicum ATCC 824 were successfully overexpressed in C. tyrobutyricum ATCC 25755, endowing it with the ability to co-utilize sucrose, fructose and glucose in the cane molasses. As a result, the engineering strain C. tyrobutyricum ATCC 25755/scrBAK produced 18.07 g/L and 18.98 g/L butyric acid when sucrose and cane molasses were used as the carbon source, respectively. Furthermore, the medium composition and initial cane molasses concentration were optimized to make full use of the untreated cane molasses. Based on these results, 45.71 g/L butyric acid with a yield of 0.39 g/g was obtained in fed-batch fermentation, and the feedstock cost of using untreated cane molasses was decreased by ~47% when compared with the conventional glucose fermentation. This study demonstrated the potential application of C. tyrobutyricum ATCC 25755/scrBAK for economic butyric acid production from untreated cane molasses.


Assuntos
Clostridium tyrobutyricum , Ácido Butírico , Bengala , Fermentação , Melaço
8.
Artigo em Inglês | MEDLINE | ID: mdl-31988072

RESUMO

BACKGROUND: Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOE) among SLT users from the Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Urinary biospecimens were collected from adults ages 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison with exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. RESULTS: In general, SLT users (n = 448) have significantly higher concentrations of BOE to nicotine, TSNAs, and PAHs compared with never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. CONCLUSIONS: Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared with cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. IMPACT: Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern.

9.
Anal Chim Acta ; 1097: 176-185, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-31910958

RESUMO

Hepatocellular carcinoma (HCC) is a common and lethal cancer. New serum markers for detecting HCC are urgently needed. Human carboxylesterase 1 (hCE1) is an important member of the serine hydrolase superfamily and is closely related to the occurrence of HCC. It can be used as a good serum marker for early diagnosis of HCC. Here, we developed a surface enhanced Raman scattering (SERS)- based magnetic immunosensor that specifically recognizes and detects trace amounts of hCE1 in human serum via a sandwich structure consisting of a SERS tags, magnetic supporting substrates, and target antigen (hCE1). The SERS tags are 4-mercaptobenzoic acid (4-MBA)-labeled AgNPs, and the SERS supporting substrates are composed of a raspberry-like morphology of Fe3O4@SiO2@AgNPs magnetic nanocomposites surface-functionalized with a hCE1 antibody. The prepared SERS magnetic immunosensor exhibits excellent selectivity and extremely high sensitivity for hCE1 detection. The SERS signal and logarithm of hCE1 concentration presented a wide linear response range of 0.1 ng mL-1 to 1.0 mg mL-1, and the detection limit of hCE1 was 0.1 ng mL-1. The results indicate that the immunosensor can be used for the rapid determination of hCE1 in human serum without a complicated sample pre-treatment. Furthermore, the immunosensor has good reproducibility and stability, and has a promising prospect for the quantitative detection of other tumor markers in early clinical diagnosis.

10.
BMC Cancer ; 20(1): 24, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914946

RESUMO

BACKGROUND: The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS: We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS: The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS: Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.

11.
Biofabrication ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899910

RESUMO

We explore the printability of reversible networks formed by catechol functionalized PEG solutions and metal cations (Al3+, Fe3+or V3+). The printability and shape fidelity were dependent on the ink composition (metal ion type, pH, PEG molecular weight) and printing parameters (extrusion pressure and printing speed). The relaxation time, recovery rate and viscosity of the inks were analyzed in rheology studies and correlated with thermodynamic and ligand exchange kinetic constants of the dynamic bonds and the printing performance (i.e. shape fidelity of the printed structures). The relevance of the relaxation time and ligand exchange kinetics for printability was demonstrated. Cells seeded on the materials crosslinked with Al3+, Fe3+ions were viable and revealed well spread morphologies during 7-day culture, indicating the potential of the formulations to be used as inks for cell encapsulation. The proposed dynamic ink design offers significant flexibility for 3D bioprinting, and enables straightforward adjustment of the printable formulation to meet application-specific needs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31915141

RESUMO

BACKGROUND: There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco. METHODS: Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose. RESULTS: Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑2,3-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑2,3-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake. CONCLUSIONS: Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens. IMPACT: This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.

13.
Amyloid ; 27(1): 36-44, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31635489

RESUMO

Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes.Results: Four recurrent mutations were identified by TGS and verified by Sanger sequencing: ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS.Conclusions: In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.

14.
Food Chem Toxicol ; 135: 110941, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31697970

RESUMO

Bamboo leaves soups were subjected to in vitro digestion (including separated oral, gastric and small intestinal digestions, and complete digestion containing above three stages), and their phenolics and antioxidant activities were determined. Compared to control groups, total phenolic content (TPC) in treated groups (including undigested and digested groups) increased at gastric digestion stage but decreased at other digestion stages, and the decrease in small intestinal digestion stage (19.97%) was nearly the same with that in complete digestion stage (19.39%). The antioxidant activity in digested groups almost changed accordingly to their TPC but with no significant difference (p > 0.05) as compared with undigested groups; similar results were found in four main individual phenolics including cryptochlorogenic acid, chlorogenic acid, neochlorogenic acid and isoorientin, and their contents were negatively correlated to the pH value of digestion buffers (-0.68 < r < -0.80, p < 0.01). These results indicated that the change of phenolic content and antioxidant activity in digested bamboo leaves soups mainly resulted from the pH of digestion buffers rather than digestive enzymes. In addition, the decrease of phenolics may mainly occur at small intestinal digestion stage where the pH value is the highest in the digestive system.


Assuntos
Digestão , Depuradores de Radicais Livres/química , Fenóis/química , Extratos Vegetais/química , Folhas de Planta/química , Poaceae/química , Depuradores de Radicais Livres/análise , Fenóis/análise , Extratos Vegetais/análise
15.
Dalton Trans ; 49(3): 583-587, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31834333

RESUMO

Polyoxometalates (POMs) are intriguing catalysts for various reactions. However, the function of their counter-cations is overlooked. Here, we show that flexible counter-cations of methyltrioctylammonium can trigger polyoxovanadates to transform from octahedrally coordinated H2V10O284- to tetrahedrally coordinated V10O262-. This structural transformation enhances the performance tunability of POM chemistry and improves catalyst design.

16.
Surgery ; 167(2): 493-498, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31493902

RESUMO

BACKGROUND: Cardiac surgery and cardiopulmonary bypass are associated with alterations in blood pressure in the perioperative period, which, if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after cardiopulmonary bypass. Responsiveness of these vessels to ß-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of ß-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after ß-adrenergic stimulation. METHODS: Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. Vessels were exposed in an ex vivo model to the ß-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective ß-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of ß receptors and Western blotting were also performed. RESULTS: Microvessels showed diminished responsiveness to isoproterenol (10-6 to 10-4M) after cardiopulmonary bypass (n = 8/group, P = .01). Pretreatment with the selective ß-2 blocker ICI18.551 (10-6M) prevented isoproterenol-induced microvascular relaxation (P = .001). Forskolin-induced relaxation response was also significantly diminished after cardiopulmonary bypass (n = 4/group, P < .05 versus before cardiopulmonary bypass). No significant changes in the total protein expression of ß-1, ß-2, and ß-3 receptors were detected by western blotting or immunofluorescence. CONCLUSION: Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in ß-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation ß-2 receptors without changes in ß-adrenergic receptor abundance.

17.
Zhongguo Zhen Jiu ; 39(12): 1353-6, 2019 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-31820615

RESUMO

Depression is related to qi stagnation in the body. At present, the treatment with acupuncture for depression focuses on the theories of the governor vessel, liver, spleen, stomach and the entity of five zang organs, especially for the adult group. However, the attention to adolescent depression is insufficient. It is recorded in Internal Classic that shaoyang meridian is taken as the pivot of three yang meridians, dominates the regulating of the ascending and dispersing of yang qi and plays the key role in treatment. The authors believe that yang qi starts growing at the period of youth, to which shaoyang meridian is corresponded. It is viewed that adolescent depression is closely related to the pivot function of shaoyang. In this paper, based on the theory of "taking shaoyang as the pivot", the mechanism of adolescent depression and the acupoint selection in acupuncture treatment are explored so as to utilize this theory in the treatment of adolescent depression with acupuncture.


Assuntos
Terapia por Acupuntura , Depressão/terapia , Meridianos , Adolescente , Humanos
18.
PLoS One ; 14(12): e0225857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790488

RESUMO

Although the high-fat-diet-induced metabolic syndrome (MetS) is a precursor of human cardiac pathology, the myocardial metabolic state in MetS is far from clear. The discrepancies in metabolite handling between human and small animal models and the difficulties inherent in obtaining human tissue complicate the identification of the myocardium-specific metabolic response in patients. Here we use the large animal model of swine that develops the hallmark criteria of human MetS. Our comparative metabolomics together with transcriptomics and computational nonnegative matrix factorization (NMF) interpretation of the data exposes significant decline in metabolites related to the fatty acid oxidation, glycolysis, and pentose phosphate pathway. Behind the reversal lies decreased expression of enzymes that operate in the pathways. We showed that diminished glycogen deposition is a metabolic signature of MetS in the pig myocardium. The depletion of glycogen arises from disbalance in expression of genes that break down and synthesize glycogen. We show robust acetoacetate accumulation and activated expression of key enzymes in ketone body formation, catabolism and transporters, suggesting a shift in fuel utilization in MetS. A contrasting enrichment in O-GlcNAcylated proteins uncovers hexosamine pathway and O-GlcNAcase (OGA) expression involvement in the myocardial response to MetS. Although the hexosamine biosynthetic pathway (HBP) activity and the availability of the UDP-GlcNAc substrate in the MetS myocardium is low, the level of O-GlcNacylated proteins is high as the O-GlcNacase is significantly diminished. Our data support the perception of transcriptionally driven myocardial alterations in expression of standard fatty acids, glucose metabolism, glycogen, and ketone body related enzymes and subsequent paucity of their metabolite products in MetS. This aberrant energy metabolism in the MetS myocardium provide insight into the pathogenesis of CVD in MetS.

19.
Psychol Res Behav Manag ; 12: 973-981, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802957

RESUMO

Background: The newly revised Children Neuropsychological and Behavior Scale (CNBS-R2016) is a diagnostic assessment tool widely used in China to assess the developmental level of children aged 0 to 6 years. The purpose of this study was to determine whether the effectiveness of developmental assessment in children with autism spectrum disorder (ASD) by the CNBS-R2016 was consistent with that of the Griffiths Mental Development Scales for China (GDS-C). Methods: In total, 139 children with ASD were recruited in this study. The Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to measure ASD severity. All subjects were evaluated with both the CNBS-R2016 and GDS-C. To determine the consistency between the CNBS-R2016 and GDS-C, Pearson correlation coefficients and Bland-Altman plots were computed. The GDS-C was used as a reference assessment, and the performance of the CNBS-R2016 was analyzed with receiver operating curves. Results: No significant difference was found between the proportions of developmental delays detected by the CNBS-R2016 subscales and the corresponding GDS-C subscales. The CNBS-R2016 Communication Warning Behavior subscale quotients and the total ABC and CARS scores were significantly and positively correlated. The general and subscale quotients of the CNBS-R2016 and the corresponding quotient of the GDS-C were also significantly and positively correlated. The area under all the curves of the CNBS-R2016 was above 0.8 according to the results of the GDS-C (general or subscale quotient <70 indicates a developmental delay), and Bland-Altman plots showed no systemic bias between the two scales. Conclusion: The CNBS-R2016 and GDS-C tests showed good consistency in the developmental assessment of children with ASD. In addition, the CNBS-R2016 allows the simultaneous assessment of autism symptoms and the developmental level. Therefore, the CNBS-R2016 is worthy of clinical application in children aged 0-6 years.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31840399

RESUMO

A solid-to-hollow evolution in macroscopic structures is challenging in synthetic materials. A fundamentally new strategy is reported for guiding macroscopic, unidirectional shape evolution of materials without compromising the material's integrity. This strategy is based on the creation of a field with a "swelling pole" and a "shrinking pole" to drive polymers to disassemble, migrate, and resettle in the targeted region. This concept is demonstrated using dynamic hydrogels containing anchored acrylic ligands and hydrophobic long alkyl chains. Adding water molecules and ferric ions (Fe3+ ) to induce a swelling-shrinking field transforms the hydrogels from solid to hollow. The strategy is versatile in the generation of various closed hollow objects (for example, spheres, helix tubes, and cubes with different diameters) for different applications.

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