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BACKGROUND: Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored. METHODS: Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Æs), conduit strain (Æe) and booster strain (Æa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed. RESULTS: 247 subjects (mean age 71 years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Æe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Æe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded. CONCLUSION: Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.
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(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.
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Aorta , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Aorta/diagnóstico por imagem , Aorta/fisiologia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Velocidade do Fluxo Sanguíneo/fisiologia , Adulto , Idoso , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador/métodos , Inteligência Artificial , Estudos de CoortesRESUMO
Loss of ARID1A has been reported to drive the progression of lung adenocarcinoma, yet the underlying mechanism remains elusive. In this study, we performed secretome analysis to identify the key secreted proteins regulating lung adenocarcinoma progression. We showed that the VASN level was significantly elevated in the conditioned medium from ARID1A-depleted A549 and H1299 cells. Restoration of ARID1A in ARID1A-depleted lung adenocarcinoma cells prevented the upregulation and secretion of VASN. Clinical analysis demonstrated a negative correlation between ARID1A and VASN expression in ARID1A-mutated lung adenocarcinomas. The patients with ARID1A-mutated lung adenocarcinoma had significantly higher concentrations of serum VASN than healthy controls. Moreover, serum VASN concentrations were associated with TNM stage, lymph node metastasis, and overall survival of the patients with ARID1A-mutated lung adenocarcinoma. Functional studies indicated that VASN overexpression potentiated the proliferation, invasion, and tumorigenesis of lung adenocarcinoma cells. Antibody neutralization of VASN suppressed the aggressiveness of ARID1A-depleted lung adenocarcinoma cells both in vitro and in vivo. Addition of recombinant VASN protein promoted the proliferation and invasion of lung adenocarcinoma cells. Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease.
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Adenocarcinoma de Pulmão , Proteínas de Ligação a DNA , Neoplasias Pulmonares , Fatores de Transcrição , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Animais , Proliferação de Células , Fenótipo , Masculino , Feminino , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Mutação , Células A549 , Pessoa de Meia-Idade , Invasividade Neoplásica , Progressão da DoençaRESUMO
Background: Diabetic nephropathy is a common acute complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Renal fibrosis is a major pathological change in diabetic nephropathy. Objective: To explore the diagnostic value of shear wave elastography (SWE) for renal fibrosis in patients with advanced diabetic nephropathy. Design: This was a retrospective study. Setting: This study was conducted in Heilongjiang Provincial Hospital. Participants: Sixty patients with diabetic nephropathy renal fibrosis who accepted therapy in our hospital from January 2021 to December 2022 (observation group, OG) and 60 healthy physical examination patients (control group, CG) in the same period were selected for the study. Interventions: All subjects were examined by conventional ultrasound and SWE. Primary Outcome Measures: (1) conventional ultrasonic parameters and SWE parameters and (2) clinical biochemical indicators. Results: Compared to CG, SCr and BUN in OG were higher, while eGFR in OG was lower (P < .05). Compared to CG, the cortical thickness of OG was less, and the cortical hardness of OG was more (P < .05). Compared to CKD4 patients, eGFR in CKD3 patients was higher, while SCr and BUN in CKD3 patients were lower (P < .05). Compared to CKD4 patients, the cortical thickness in CKD3 patients was higher, and cortical hardness in CKD3 patients was lower (P < .05). Conclusion: The cortical thickness and cortical hardness parameters in SWE imaging of patients with advanced diabetic nephropathy renal fibrosis are different from those of healthy people. The parameters are also significantly different in patients with different CKD stages and are significantly correlated with SCr, BUN, and eGFR, which can be used for the diagnosis of diabetic nephropathy renal fibrosis.
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An electrochemical sensor was developed for detecting zearalenone (ZEN) based on the mimic peptide, which was screened from the library and validated by molecular simulation and electrochemical methods. The library of the mimic peptide was constructed according to the structural analysis, molecular docking, molecular dynamics and amino acid mutation. Then, the enhanced electrical signal was attributed to gold nanoparticles (AuNPs) and reduced carboxylated graphene oxide (rGO-COOH). Under the optimal conditions, the detection limit was 0.91 pg·mL-1 (S/N = 3) with a wide linear range from 0.01 ng·mL-1 to 10 ng·mL-1. In grain samples, a good recovery rate of 84% to 105.3% was achieved, while the rate ranged from 82% to 108.8% in the commercial ELISA kits. Additionally, the electrochemical sensor exhibited the remarkable specificity, excellent stability and better reproducibility (RSD = 1.94%). This sensor has great potential for rapidly detecting ZEN in food.
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Técnicas Eletroquímicas , Contaminação de Alimentos , Ouro , Grafite , Nanopartículas Metálicas , Peptídeos , Zearalenona , Zearalenona/análise , Técnicas Eletroquímicas/instrumentação , Grafite/química , Contaminação de Alimentos/análise , Ouro/química , Nanopartículas Metálicas/química , Peptídeos/química , Limite de Detecção , Simulação de Acoplamento Molecular , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodosRESUMO
As the central hub of the secretory pathway, the Golgi apparatus plays a crucial role in maintaining cellular homeostasis in response to stresses. Recent studies have revealed the involvement of the Golgi tether, GORASP2, in facilitating autophagosome-lysosome fusion by connecting LC3-II and LAMP2 during nutrient starvation. However, the precise mechanism remains elusive. In this study, utilizing super-resolution microscopy, we observed GORASP2 localization on the surface of autophagosomes during glucose starvation. Depletion of GORASP2 hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A. Furthermore, we found that GORASP2 controls RAB7A activity by modulating its GEF complex, MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex. The assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes was also attenuated without GORASP2. These findings suggest that GORASP2 helps seal autophagosomes and activate the RAB7A-HOPS-SNAREs membrane fusion machinery for autophagosome maturation, highlighting its membrane tethering function in response to stresses.Abbreviations: BafA1: bafilomycin A1; ESCRT: endosomal sorting complex required for transport; FPP: fluorescence protease protection; GEF: guanine nucleotide exchange factor; GFP: green fluorescent protein; GORASP2: golgi reassembly stacking protein 2; GSB: glucose starvation along with bafilomycin A1; HOPS: homotypic fusion and protein sorting; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PK: proteinase K; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SIM: structured illumination microscopy; UVRAG: UV radiation resistance associated.
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The high-altitude real-time inspection of unmanned aerial vehicles (UAVs) has always been a very challenging task. Because high-altitude inspections are susceptible to interference from different weather conditions, interference from communication signals and a larger field of view result in a smaller object area to be identified. We adopted a method that combines a UAV system scheduling platform with artificial intelligence object detection to implement the UAV automatic inspection technology. We trained the YOLOv5s model on five different categories of vehicle data sets, in which mAP50 and mAP50-95 reached 93.2% and 71.7%, respectively. The YOLOv5s model size is only 13.76 MB, and the detection speed of a single inspection photo reaches 11.26 ms. It is a relatively lightweight model and is suitable for deployment on edge devices for real-time detection. In the original DeepStream framework, we set up the http communication protocol to start quickly to enable different users to call and use it at the same time. In addition, asynchronous sending of alarm frame interception function was added and the auxiliary services were set up to quickly resume video streaming after interruption. We deployed the trained YOLOv5s model on the improved DeepStream framework to implement automatic UAV inspection.
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An efficient protocol of enantioselective thiolative azidation of sulfone-tethered alkenes via a chiral chalcogenide catalyzed electrophilic reaction is disclosed. A series of enantioenriched sulfones bearing remote stereogenic centers was achieved with good yields and high enantioselectivities with linear unsaturated sulfones and cyclic unsaturated sulfones. Mechanistic studies revealed the importance of the sulfone group in the improvement of the reactivity and enantioselectivity of the reaction.
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In animal cells, the Golgi apparatus serves as the central hub of the endomembrane secretory pathway. It is responsible for the processing, modification, and sorting of proteins and lipids. The unique stacking and ribbon-like architecture of the Golgi apparatus forms the foundation for its precise functionality. Under cellular stress or pathological conditions, the structure of the Golgi and its important glycosylation modification function may change. It is crucial to employ suitable methodologies to study the structure and function of the Golgi apparatus, particularly when assessing the involvement of a target protein in Golgi regulation. This article provides a comprehensive overview of the diverse microscopy techniques used to determine the specific location of the target protein within the Golgi apparatus. Additionally, it outlines methods for assessing changes in the Golgi structure and its glycosylation modification function following the knockout of the target gene.
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Compared to well-developed catalytic 1,2-diazidation of alkenes to produce vicinal diazides, the corresponding catalytic 1,1-diazidation of alkenes to yield geminal diazides has not been realized. Here we report an efficient approach for catalytic 1,1-diazidation of alkenes by redox-active selenium catalysis. Under mild conditions, electron-rich aryl alkenes with Z or E or Z/E mixed configuration can undergo migratory 1,1-diazidation to give a series of functionalized monoalkyl or dialkyl geminal diazides that are difficult to access by other methods. The method is also effective for the construction of polydiazides. The formed diazides are relatively safe by TGA-DSC analysis and impact sensitivity tests, and can be easily converted into various valuable molecules. In addition, interesting reactivity that geminal diazides give valuable molecules via the geminal diazidomethyl moiety as a formal leaving group in the presence of Lewis acid is disclosed. Mechanistic studies revealed that a selenenylation-deselenenylation followed by 1,2-aryl migration process is involved in the reactions, which provides a basis for the design of new reactions.
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Aging-induced aortic stiffness has been associated with altered fatty acid metabolism. We studied aortic stiffness using cardiac magnetic resonance (CMR)-assessed ventriculo-arterial coupling (VAC) and novel aortic (AO) global longitudinal strain (GLS) combined with targeted metabolomic profiling. Among community older adults without cardiovascular disease, VAC was calculated as aortic pulse wave velocity (PWV), a marker of arterial stiffness, divided by left ventricular (LV) GLS. AOGLS was the maximum absolute strain measured by tracking the phasic distance between brachiocephalic artery origin and aortic annulus. In 194 subjects (71 ± 8.6 years; 88 women), AOGLS (mean 5.6 ± 2.1%) was associated with PWV (R = -0.3644, p < 0.0001), LVGLS (R = 0.2756, p = 0.0001) and VAC (R = -0.3742, p <0.0001). Stiff aorta denoted by low AOGLS <4.26% (25th percentile) was associated with age (OR 1.13, 95% CI 1.04-1.24, p = 0.007), body mass index (OR 1.12, 95% CI 1.01-1.25, p = 0.03), heart rate (OR 1.04, 95% CI 1.01-1.06, p = 0.011) and metabolites of medium-chain fatty acid oxidation: C8 (OR 1.005, p = 0.026), C10 (OR 1.003, p = 0.036), C12 (OR 1.013, p = 0.028), C12:2-OH/C10:2-DC (OR 1.084, p = 0.032) and C16-OH (OR 0.82, p = 0.006). VAC was associated with changes in long-chain hydroxyl and dicarboxyl carnitines. Multivariable models that included acyl-carnitine metabolites, but not amino acids, significantly increased the discrimination over clinical risk factors for prediction of AOGLS (AUC [area-under-curve] 0.73 to 0.81, p = 0.037) and VAC (AUC 0.78 to 0.87, p = 0.0044). Low AO GLS and high VAC were associated with altered medium-chain and long-chain fatty acid oxidation, respectively, which may identify early metabolic perturbations in aging-associated aortic stiffening. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.
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Envelhecimento , Ácidos Graxos , Oxirredução , Análise de Onda de Pulso , Rigidez Vascular , Humanos , Feminino , Masculino , Idoso , Rigidez Vascular/fisiologia , Ácidos Graxos/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Aorta/diagnóstico por imagem , Pessoa de Meia-Idade , Imagem Cinética por Ressonância Magnética/métodos , Idoso de 80 Anos ou mais , Ventrículos do Coração/metabolismo , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologiaRESUMO
Enantioselective difunctionalization of alkenes offers a straightforward means for the rapid construction of enantioenriched complex molecules. Despite the tremendous efforts devoted to this field, enantioselective aminative difunctionalization remains a challenge, particularly through an electrophilic addition fashion. Herein, we report an unprecedented approach for the enantioselective aminative difunctionalization of alkenes via copper-catalyzed electrophilic addition with external azo compounds as nitrogen sources. A series of valuable cyclic hydrazine derivatives via either [3 + 2] cycloaddition or intramolecular cyclization have been achieved in high chemo-, regio-, enantio-, and diastereoselectivities. In this transformation, a wide range of functional groups, such as carboxylic acid, hydroxy, amide, sulfonamide, and aryl groups, could serve as nucleophiles. Importantly, a new cyano oxazoline chiral ligand was found to play a crucial role in the control of enantioselectivity.
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PURPOSE: The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root. METHODS: This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC. RESULTS: For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p<0.001. A threshold of >8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p<0.001 for visual vortex flow. Manual systolic rotational flow angle change (ΔsRA) demonstrated excellent association with semiautomated ΔsRA (r=0.99, 95% CI 0.9907 to 0.999, p<0.001). In reproducibility testing, average systolic FD (FDsavg) showed a minimal bias at 1.28% with a high intraclass correlation coefficient (ICC=0.92). Similarly, sFRR had a minimal bias of 1.14% with an ICC of 0.96. ΔsRA demonstrated an acceptable bias of 5.72°-and an ICC of 0.99. CONCLUSION: 2D PC flow imaging can possibly quantify blood flow helicity (ΔRA) and vorticity (FRR). These imaging biomarkers of flow helicity and vorticity demonstrate high reproducibility for clinical adoption. TRIALS REGISTRATION NUMBER: NCT05114785.
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Estenose da Valva Aórtica , Imageamento por Ressonância Magnética , Humanos , Coração , Hemodinâmica , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Estudo de Prova de ConceitoRESUMO
Antibacterial photodynamic therapy (aPDT) has emerged as a promising strategy for treating periodontitis. However, the weak binding of most photosensitizers to bacteria and the hypoxic environment of periodontal pockets severely hamper the therapeutic efficacy. Herein, two novel oxygen-independent photosensitizers are developed by introducing selenophene into viologens and modifying with hexane chains (HASeV) or quaternary ammonium chains (QASeV), which improve the adsorption to bacteria through anchoring to the negatively charged cell membrane. Notably, QASeV binds only to the bacterial surface of Porphyromonas gingivalis and Fusobacterium nucleatum due to electrostatic binding, but HASeV can insert into their membrane by strong hydrophobic interactions. Therefore, HASeV exhibits superior antimicrobial activity and more pronounced plaque biofilm disruption than QASeV when combined with light irradiation (MVL-210 photoreactor, 350-600 nm, 50 mW/cm2), and a better effect on reducing the diversity and restoring the structure of subgingival flora in periodontitis rat model was found through 16S rRNA gene sequencing analysis. The histological and Micro-CT analyses reveal that HASeV-based aPDT has a better therapeutic effect in reducing periodontal tissue inflammation and alveolar bone resorption. This work provides a new strategy for the development of viologen-based photosensitizers, which may be a favorable candidate for the aPDT against periodontitis.
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Periodontite , Fotoquimioterapia , Animais , Ratos , Fármacos Fotossensibilizantes/uso terapêutico , RNA Ribossômico 16S , Periodontite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Inflamação/tratamento farmacológico , Bactérias , Porphyromonas gingivalisRESUMO
Background: Pulmonary artery (PA) strain is associated with structural and functional alterations of the vessel and is an independent predictor of cardiovascular events. The relationship of PA strain to metabolomics in participants without cardiovascular disease is unknown. Methods: In the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling. PA global longitudinal strain (GLS) analysis was performed by tracking the change in distance from the PA bifurcation to the pulmonary annular centroid, using standard cine CMR images. Circulating metabolites were measured by cross-sectional targeted metabolomics analysis. Results: Among n = 170 adults (mean age 71 ± 6.3 years old; 79 women), mean values of PA GLS were 16.2 ± 4.4%. PA GLS was significantly associated with age (ß = -0.13, P = 0.017), heart rate (ß = -0.08, P = 0.001), dyslipidemia (ß = -2.37, P = 0.005), and cardiovascular risk factors (ß = -2.49, P = 0.001). Alanine (ß = -0.007, P = 0.01) and proline (ß = -0.0009, P = 0.042) were significantly associated with PA GLS after adjustment for clinical risk factors. Medium and long-chain acylcarnitines were significantly associated with PA GLS (C12, P = 0.027; C12-OH/C10-DC, P = 0.018; C14:2, P = 0.036; C14:1, P = 0.006; C14, P = 0.006; C14-OH/C12-DC, P = 0.027; C16:3, P = 0.019; C16:2, P = 0.006; C16:1, P = 0.001; C16:2-OH, P = 0.016; C16:1-OH/C14:1-DC, P = 0.028; C18:1-OH/C16:1-DC, P = 0.032). Conclusion: By conventional CMR, PA GLS was associated with aging and vascular risk factors among a contemporary cohort of older adults. Metabolic pathways involved in PA stiffness may include gluconeogenesis, collagen synthesis, and fatty acid oxidation.
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Generation of sulfate radicals (SO4â¢-) from sulfite activation has emerged as a promising method for abatement of organic pollutants in the water and wastewater treatment. Co(II) has garnered attention due to its high catalytic activity in the sulfite activation, which is compromised by the slow Co(II)/Co(III) redox cycling. Regarding the regulation of Co(II) electronic structure via the complexation effect, monoethanolamine (MEA), a common chelator, is introduced into the Co(II)/sulfite system. MEA addition results in a significant improvement in iohexol abatement efficiency, increasing from 40% to 92%. The superior iohexol abatement relies on the involvement of SO4â¢-, hydroxyl radicals (HOâ¢) and Co(IV). Hydrogen radical (â¢H) is unexpectedly detected, acting as a strong reducing agent, contributing to the reduction of Co(III). This enhancement of sulfite activation by MEA is due to the formation of the Co(II)-MEA complex, in which the complexation ratio of Co(II) and MEA is critical. Electrochemical characterization and theoretical calculations demonstrate that the complexation can facilitate the Co(II)/Co(III) redox cycling with the concomitant enhancement of sulfite activation. This work provides a new insight into the Co(II)/sulfite system in the presence of organic ligands.
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TRF2 is a component of shelterin, a telomere-specific protein complex that protects the ends of mammalian chromosomes from DNA damage signaling and improper repair. TRF2 functions as a homodimer and its interaction with telomeric DNA has been studied, but its full-length DNA-binding properties are unknown. This study examines TRF2's interaction with single-DNA strands and focuses on the conformation of the TRF2-DNA complex and TRF2's preference for DNA chirality. The results show that TRF2-DNA can switch between extended and compact conformations, indicating multiple DNA-binding modes, and TRF2's binding does not have a strong preference for DNA supercoiling chirality when DNA is under low tension. Instead, TRF2 induces DNA bending under tension. Furthermore, both the N-terminal domain of TRF2 and the Myb domain enhance its affinity for the telomere sequence, highlighting the crucial role of multivalent DNA binding in enhancing its affinity and specificity for telomere sequence. These discoveries offer unique insights into TRF2's interaction with telomeric DNA.
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Complexo Shelterina , Proteína 2 de Ligação a Repetições Teloméricas , Animais , Telômero/genética , Telômero/metabolismo , DNA/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Mamíferos/genéticaRESUMO
The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.
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Bacteriocinas , Microbiota , Humanos , Bacteriocinas/metabolismo , Bacteriocinas/farmacologia , Inteligência Artificial , Trato Gastrointestinal/metabolismo , EstômagoRESUMO
OBJECTIVES: Cardiovascular magnetic resonance (CMR) imaging is routinely performed for assessing right ventricular (RV) systolic but not diastolic function. We aimed to investigate CMR-based assessment of RV diastolic function in pediatric patients with repaired tetralogy of Fallot (rTOF), compared to transthoracic echocardiography (TTE) measurements. METHODS: A total of 130 consecutive pediatric patients with rTOF who underwent clinically indicated CMR and same-day TTE were included. Forty-three controls were recruited. Phase-contrast images were used to measure trans-tricuspid valve flow velocities during early (E) and late diastolic (A) phases (measured in cm/s). Feature tracking of the tricuspid annulus was performed to derive early (e') and late diastolic (a') myocardial velocities (measured in cm/s). RV diastolic function was evaluated by E/A ratio, E/e' ratio, and E-wave deceleration time (measured in milliseconds). Regression analyses were utilized to identify potential variables associated with RV diastolic dysfunction (DD). The performance of CMR-derived parameters in diagnosing RV DD was assessed using receiver-operating characteristic analyses. RESULTS: Good agreement was found between CMR and TTE measurements (ICC 0.70-0.89). Patients with RV DD (n = 67) showed significantly different CMR-derived parameters including E and e' velocities, and E/A and E/e' ratio, compared to patients without DD (n = 63) (all p < 0.05). CMR-derived E and e' velocities and E/e' ratio were independent predictors of RV DD. E/e' of 5.8 demonstrated the highest discrimination of RV DD (AUC 0.76, sensitivity 70%, specificity 86%). CONCLUSIONS: CMR-derived parameters showed good agreement with TTE parameters in determining RV DD. CMR-derived E/e' was proved to be the most effective in identifying RV DD. CLINICAL RELEVANCE STATEMENT: This study demonstrated the feasibility and efficacy of CMR in assessing diastolic function in pediatric patients. RV DD was presented in over half of patients according to current TTE guidelines, highlighting the need for assessing RV diastolic function during follow-up. KEY POINTS: ⢠Routinely acquired cine and phase-contrast cardiovascular magnetic resonance (CMR) images yielded right ventricular (RV) diastolic parameters which demonstrated good agreement with transthoracic echocardiography (TTE) measurements. ⢠There was a high prevalence of RV diastolic function impairment in pediatric patients with repaired tetralogy of Fallot (rTOF). ⢠CMR is a reliable complementary modality of TTE for RV diastolic function evaluation.